Archive for the ‘Chromosomes’ Category

Tracking The Advance Of Modernity By The Hybrid Nature Of IBD Segments – The Depletion Of Our Hybrid Heritage Revisited

April 28, 2014 6 comments

The implications of short DNA segment sharing between populations in Africa, Europe and Asia are compelling. Povysil and Hochreiter (2014), Austrian researchers on the Institute of Bioinformatics in Linz, published a preprint on new results that focus on population structure, based on the genetic heritage of humans, Neandertals and Denisovans. Applying HapFABIA, a new method for the identification of very short identity by descent (IBD) segments tagged by rare SNVs (single nucleotide variants) or tagSNVs, for now just based on chromosome 1 data from the 1000 Genomes Project (Phase 1, actually consisting of 1,092 individuals: 246 Africans, 181 Admixed Americans, 286 East Asians, and 379 Europeans), 105,652 valid IBD segments were detected:

The vast majority (101,209) of the detected IBD segments (105,652) is shared by Africans (at least one African possesses the segment), of which 64,894 are exclusively found in Africans. Only 9,003 and 4,793 IBD segments are shared by Europeans and Asians, respectively. 558 IBD segments are exclusively found in Europeans and 1,452 exclusively in Asians. (Povysil et al., 2014)

Mapping these results against the Denisovan genome at 31X coverage (Meyer et al., 2012), and the Altai Neandertal genome at 52X coverage (Prüfer et al., 2014), resulted in a global division into segments that are Neanderthal-like, Denisovan-like, or “Archaic”, ie. matching both the Denisova and Neandertal genome. Intercontinental sharing of segments should thus provide some indication of origin and post-admixture gene flow between the continents.


Researchers have genomes from three types of humans who coexisted during the last Ice Age: Neandertals (orange); Denisovans (blue); and Homo sapiens (yellow). Interbreeding was attested for the Denisovan and the modern human samples.

This focus on the current distribution of purported Neanderthal, Denisovan and “Archaic” IBD segments is a valuable extension to previous previous results described in Hochreiter’s “Rare Haplotypes in the Korean Population” (2012) and “HapFABIA: Identification of very short segments of identity by descent characterized by rare variants in large sequencing data” (2013) that still may not have received due attention or assessment yet. The inflated portion of European-African shared DNA snippets in the African-European-Asian triangle already caught my attention in Expanding Hybrids And The Rise Of Our Genetic Common Denominator. It goes without saying that Asians should have more archaic DNA than Europeans, but despite the total Neanderthal contribution being apparently higher in the Asian genome, I found the accumulated European contribution as compared to the Asian contribution to be consistently higher for rare DNA segments. Due to different filtering and standards the quantitative differences were even more extreme for the 2014 preprint (8,6% European versus 4,6% Asian) than in mentioned previous publications (2012: 8,4% versus 6,1%; 2013: 11,8% versus 6,8%). Remarkably, this combines with an even more massive attestation of European-African shared segments, while Asian segments remain hardly shared by Africans. Reluctance to subsequently consider this shared European-African portion as essentially European seems to be the logical consequence of embracing Out of Africa. However, the African tendency for smaller sized IBD segments being noted in the preprint, doesn’t equally involve the shared European-African portion at all. Hochreiter et al. (2013)’s Figure 8 already revealed that the distribution curves of “Neanderthal” segment sizes don’t differ so much between Asian and European samples, as compared with on average shorter African samples. All the contrary, compared with the Asian reference the European curve in figure 29A of the preprint (2014) reveals a slight left-shift for the private Neanderthal-like IBD segments towards smaller sequences than the overall European “Neanderthal” distribution in figure 28B, suggesting the European IBD segments of the African shared part are on average distinguishably longer than typical for private African IBD segments. According to figure 23 also the overall Asian left-shift for African shared IBD segments is considerably higher than for Europe, though apparently this feature doesn’t involve the Neanderthal-like part. Actually, instead the right-shift of private Asian “Neanderthal” segments is closely linked with the Asian excess of Neanderthal DNA, apparently without this having resulted in a higher count of Asian IBD segments. Thus, the African tendency for smaller IBD segments as being noted in the preprint, seems to be separate from the shared European-African “Neanderthal” distribution! To the effect that a considerable part of African variation can actually be derived from the European distribution.
Actually, Europeans have more variation than Asians as they share more different IBD segments. Indeed, on average (Castellano et al., 2014) European heterozygosity (0.387 per thousand coding bases) is also higher than Asian heterozygosity (0.358), what is far less than African heterozygosity (0.507) and much higher than Neanderthal heterozygosity (0.128). Since ‘about 33% of the derived alleles seen in the Neandertals are shared with the present-day humans and about 19%, 24%, and 24% of the derived alleles seen in the Africans, Europeans, and Asians, respectively, are shared with the Neandertals’ (Castellano et al., 2014), it may be confirmed that Neanderthal-derived variability in Europe should be slightly higher for Europeans than Asians, and considerably higher for Africans.
After having filtered out the IBD segments being already present in the ancestral genome of humans and other primates, the preprint presents an interesting interbreeding analysis. On average more Asians share the few IBD segment, indicating less variation and genetic unity. Indeed, this may confirm East Asians as a rather recent population expansion. Or a bottleneck, if this would also suggest a previous reduction of population size involving some hypothesized similar hybrid population. At least, the East Asian element was not visible yet in Mal’ta Boy (24,000 BP), found pretty deep inside current Mongoloid territory. A late East Asian expansion may even be corroborated by the genetic results of Tianyuan if, like I already suggested in Restoring the Gap, Part 1 – The Delayed Non-African Expansions of Modernity, Tianyuan was actually less East Asian than could be expected from its location. Bottleneck rather than population expansion may possibly be evidenced in Native Americans. Some pre-bottleneck variation of the kind may have been preserved in South East Asia. Unfortunately, these regions were not yet included in the Phase 1 samples of the 1000 Genomes Project. So far I tend to consider the East Asian component in Native Americans and (Island) Southeast Asia rather part of some more recent East Asian expansion.
For reading the IBD length distribution graphs it should be considered that overlap of different distribution curves may have produced a somewhat convolute results, where the peaks that emerge may really derive from superposed distribution curves having density peaks at quite different segment lengths. Like in wave theory distribution curves may combine through superposition to create an interference pattern that feature distinct metrics, ie. the density peaks we see might be deceiving and actually derive from a combination of underpinning “hidden” density peaks. Retrieving actual distribution curves as components of the visible part may be complex and reminds me to the geophysical maps I once had to interpret as a student using deconvolution.
Remember, each distribution curve may be modeled as the statistical result of random segment length reduction into smaller segments as a function of time, and overlap between distribution curves may cause interference. Each distribution curve may decompose into its constituent elements that reflect another admixture event or regions of low recombination rate. Real-life dependencies such as geography, genetic cohesion and natural selection are likely to have influenced, or “distorted”, the statistical distribution curves.
For instance, Asians and Europeans have very similar IBD lengths distributions though both have some minor peaks at longer segments where the distribution curves deviate. Here the chromosome cross-over process may have been retained due to a combination of natural selection, sweep and possibly a higher proportion of homozygous cross-over events. One way to find out about the underpinning reasons for the resulting convolute distribution curve is find a procedure to decompose the overall curves into their constituent components by using proper deconvolution tools and proper assumptions.

The authors of the preprint did some decomposing themselves in the panels of chapter 4 “Analyses of Lengths of IBD Segments”, using a coarse geographic grid. This already yielded an interesting array of distinct distribution curves on a geographical basis that either appear independent or sharing some dependencies. Without any doubt a denser grid of regional human genome samples would help identify more constituent distribution curves, or admixture events, though probably not for each and every minor peak if these were due to uneven effects of natural selection. The best way to assess the nature of all spikes and anomalies of all the distribution curves would be to run the analyses on all human chromosomes separately, what the authors indeed intend to do. While the preprint only presents preliminary results on chromosome 1 of the 1000 Genomes Project, this will soon be completed with results from the other chromosomes for the final version.

figure 23

Figure 23 (Povysil et al., 2014): For Asian there is a clear bias to shorter IBD segments if they are shared with Africans. For Europeans this effect is less clear.

Let’s take a closer look at the various distribution curves for IBD segment lengths of figures 23-31, on the intuitive though – as demonstrated below – precarious assumption of an inverse relation between mean segment size and age. Figure 23 shows a noticeable signal of smaller sequences in Asia for the portion of IBD segments being shared with Africa, while for Europe the signal for an African shared ancestry background is only significant for the smallest segments below 10,000 base pairs (bp). Figure 24 shows this ancestry background signal is stronger for Europe than Asia if European/Asian/African shared segments are included, implying Europe may have played some role in transmitting small segments to Asia. Instead, Figure 25 shows that on average shared Eurasian segments are longer than private European or Asian segments, implying longer segments distributed more easily eg. by the process of natural selection than smaller segments. Where did these longer segments come from, and what pattern followed the early distribution of smaller segments outside Africa?
The next figures distinguish three types of IBD segments, ie. Neanderthal-like, Denisovan-like and “Archaic”, that are neither Neanderthal or Denisovan. For each type the segment length distribution is related to its global geographical location, for either “shared” segments that occur in various continents, or for “private” segments, that occur in a single continent only. Thus, figures 26 and 27 display geographically shared and private Denisovan segments respectively; figures 28 and 29 respectively display shared and private Neanderthal-like segments; and figures 30 and 31 display respectively shared and private “Archaic” segments.
figure 24

Figure 24 (Povysil et al., 2014): If European/Asian/African shared segments are included the African ancestry background signal is stronger for Europe than Asia, implying Europe may have played some role in transmitting small segments to Asia.

figure 25

Figure 25 (Povysil et al., 2014): On average the shared Eurasian segments are longer than private European or Asian segments, implying longer segments distributed more easily, eg. by the process of natural selection, than smaller segments.

The next figures distinguish three types of IBD segments, ie. Neanderthal-like, Denisovan-like and “Archaic”, that are neither Neanderthal or Denisovan. For each type the segment length distribution is related to its global geographical location, for either “shared” segments that occur in various continents, or for “private” segments, that occur in a single continent only. Thus, figures 26 and 27 display geographically shared and private Denisovan segments respectively; figures 28 and 29 respectively display shared and private Neanderthal-like segments; and figures 30 and 31 display respectively shared and private “Archaic” segments.
figure 26

Figure 26 (Povysil et al., 2014): The convoluted overall European distribution curve that match the Denisovan genome (fig.26B) has density peaks at 28,000 and 37,500 bp that may both be shared Eurasian.

figure 27 (Povysil et al., 2014): IBD segments that match the Denisovan genome have a straightforward private European component (fig.27A, density peaks at 12,000 and 46,000 bp).

Figure 27 (Povysil et al., 2014): IBD segments that match the Denisovan genome have a straightforward private European component (fig.27A, density peaks at 12,000 and 46,000 bp).

The convolute state for the European length distribution of IBD segments that match the Denisovan genome (fig.26B) has a straightforward private European component (fig.27A, density peaks at 12,000 and 46,000 bp). This means much of the European Denisovan-like segments are shared by other continents. Instead, the Asian distribution of the private component (fig.27A) is only slightly more spiked (peaks at 27,000, 40,000, 54,000 bp) than the overall Asian distribution (fig.26B), betraying few non-Asian influences here. More specifically, the convoluted overall European distribution curve (fig.26B) has additional peaks at 28,000 and 37,500 bp that may both be shared Eurasian.
Figure 29A shows a convolute state for the distribution of length for private European IBD segments that match the Neanderthal genome (peaks at 15,500 and 26,500 bp), approaching only the Asian distribution (not the African!) when shared segments are included (fig.28B). Apparently, Asians have their wide distribution curve and main density peak at 26,000 bp (nearly) in common with Europe.
figure 28 (Povysil et al., 2014): The distribution curves of IBD segments that match the Neanderthal genome and include geographically shared segments, are similar between Europe and Asia, but not for Africa (fig.28B).

Figure 28 (Povysil et al., 2014): The distribution curves of IBD segments that match the Neanderthal genome and include geographically shared segments, are similar between Europe and Asia, but not for Africa (fig.28B).

figure 29

Figure 29 (Povysil et al., 2014): A private European density peak at 15,500 bp is accompanied by a left shift towards smaller IBD segments, indicating an admixture event that is almost exclusively reminiscent in Europe.

The wide European (Neanderthal) and Asian (Neanderthal and Denisovan) distribution curves having peaks between 26,000 – 28,000 bp have all appearance to be due to contemporaneous main admixture events that involved Neanderthal in Europe and Neanderthal-Denisova hybrids in Asia. Actually, for this range I fail to notice a Denisovan admixture event in Asia that is separate from Neanderthal admixture. At this point, Europe’s density peak at 15,500 for Neanderthal segments (figure 29A) could be due to selective LD latency at work, confined to Europe, since without such possibly selection-driven spikes the distribution patterns of both Europe and Asia would converge to a similar bell-shaped curve. This possibility would corroborate a similar age for Asian and European admixture events. However, since this private European density peak at 15,500 bp is accompanied by a left shift towards an overall private tendency of smaller IBD segments, this feature rather seems to indicate a preceding admixture event that is almost exclusively reminiscent in Europe.
figure 30

Figure 30 (Povysil et al., 2014): The Archaic distribution curve for Europe that peaks at 10,000 bp (fig.30A) looks wide enough to be actually a superposition of constituent elements.

figure 31

Figure 31 (Povysil et al., 2014): The lack of private “Archaic” segments of European signature near the Asian peak at 26,000 bp (fig.31A) is telling about the Asian origin of European shared “Archaic” segments having this particular distribution.

“Archaic” IBD segments, that couldn’t be identified exclusively as Neanderthal nor Denisovan, show private sister peaks for Europeans (at 34,000 bp, fig.31A) and Africans (at 33,000 bp, fig.31B). This apparently reveals the shared African-European (Mediterranean?) origin of a comparatively late admixture event, without any clear Asian affiliation.
If so, “Mediterranean” archaic segments are puzzling. Iberians feature some unexpected correlations, ie. a lower Neanderthal contribution. I am not sure this could be explained by higher rates of African gene flow: AMR populations already show that AFR admixture rather causes a boost of “ancient African” IBD segments than a reduction of verifiable archaic contribution. Unless this same pattern could be isolated from the data in a forthcoming study, it could be postulated the Denisovan and Neanderthal “deficit” in the Iberian population (figures 1 and 2) was actually caused by moving segments into the Archaic category, rather than this deficit being explained by African admixture. Indeed, the latter should have implied a massive introgression of African short IBD segments not unlike the tendency observed in the Admixed American (AMR) sample.
However, the 1000 Genome Project Phase 1 only contains Sub-Saharan African samples as a reference. “Mediterranean” could have a North African affiliation instead, while possible collateral Sub-Saharan influences as attested by the archaic segments in Europe that peak at 5000 bp in Africa can’t be excluded. I wonder if higher Neanderthal contributions attested in Ötzi and some Northern African populations may indeed be due to this apparently late admixture event, and if this wouldn’t exclude Northern Africa as an early agent of modern human genes.
Another European Archaic distribution curve that peaks at 10,000 bp (fig.30A) looks wide enough to be actually a superposition of segments associated with the fully African segments that peak at 5,000 bp (fig.31B) and fully European segments that correspond with the private density peaks for “Neanderthal” segments at 15,500 bp (fig.29A) and “Denisovan” segments at 12,000 (fig.27A, possibly a superposition all by itself). We’ve already seen the slight left-shift of the European distribution curve towards lower lengths compared with the Asian curve. The resolution of these measurement is just not high enough to be conclusive, though it is interesting these European short IBD segments may be connected and reminiscent of what may have been some of the earliest admixture events outside Africa.
Finally, the lack of private “Archaic” segments of European signature near the Asian peak at 26,000 bp (fig.31A) is telling about the Asian origin of European shared “Archaic” segments having this particular distribution.
I would conclude that the private Asian “archaic” density peak at 26,000 bp (fig.31A) fits in nicely with the other distribution curves having density peaks between 26,000 – 27,000 bp (fig.27A, private Asian “Denisovan; fig.29A, private Asian and European “Neanderthal”) that indicate a wide range of contemporaneous Eurasian admixture events involving Neanderthal in Europe and Neanderthal-Denisova hybrids in Asia. Most likely the agent of this admixture were Neanderthal populations that ‘sometimes’ already inherited such hybrid genes all by themselves.
Moreover, a large tail of density peaks could be distinguished that may or may not be relevant for assessing the admixture history of modern humans. It has to be reiterated that the dataset of 1000 Genome Project Phase 1 is limited to a very course grid of East Asians, Europeans, Sub-Saharan Africans plus some mixed American populations, all of whom were so far only analyzed for IBD segments on chromosome 1. For instance, the large chunks of Denisovan DNA discovered in Oceania were not examined. This having said, the largest IBD segments may rather be an indication of long time isolation of already admixed populations, since higher levels of homozygosity imply lower rates of DNA segment size decay by cross-over.
In summary, on top of a Sub-Saharan multitude of small sized IBD segments, largely confined to the African continent, a coarse grid of admixed IBD segment subsets in different grades of size decay may be perceived, or admixture layers on a world-wide scale, that for now could be distinguished as follows:

    1. An early “European” layer of Neanderthal-like, Denisovan-like and “Archaic” IBD segments having a (projected) density peak at about 15,000 bp
    2. A “Eurasian” layer of basically Neanderthal-like IBD segments, supplemented in East Asia by Denisovan-like IBD segments, having a density peak at about 26,000-27,000 bp
    3. A “Mediterranean” subset of “Archaic” IBD segments having a density peak at about 34,000 bp
    4. A “Eurasian” layer of basically Neanderthal-like IBD segments, supplemented in East Asia by Denisovan-like IBD segments, having a density peak at about 40,000-42,000 bp
    5. A European (and possibly shared Asian) tail of “Denisovan” IBD segments having a density peak at about 45,000 bp
    6. An Asian tail of “Denisovan” IBD segments having a density peak at about 54,000 bp
    7. A European tail of “Neanderthal” IBD segments having a density peak at about 56,000 bp

It remains to be seen how many of these categories will persist once the dataset has been extended to include all chromosomes. Once the effects of natural selection and regions of low recombination rate are filtered out, and the subsets of restricted geographic currency tightly assigned to conservative regions where isolated populations could retain their homozygosity and larger IBD segments much longer since admixture – as possibly the case in Northern Africa (subset 3) – the true admixture story could be revealed.
Let’s first try to map these different density peaks on the current insights that concern the expansion of modernity. Purported ‘evidence for a single dispersal […] during a rapid worldwide expansion out of Africa in the Late Pleistocene’ dictated the prevailing view on modern human origins for a long time. Strange enough, most often a coastal route through south Asia was sought for the initial, single dispersal event out of Africa, nowadays dated ‘as early as ~130 ka ago‘ – while ‘in comparative craniometric studies the Levantine series and other early modern humans from Africa have consistently closer affinity to recent Australians than to other modern human populations’. Apparently, something else caused modern African population to be quite different, and other non-Australian populations as well: ‘However, recent genetic studies, as well as accumulating archaeological and paleoanthropological evidence, challenge this parsimonious model. They suggest instead a “southern route” dispersal into Asia as early as the late Middle Pleistocene, followed by a separate dispersal into northern Eurasia’ (Reyes-Centeno et al., 2014). Indeed, ‘a second dispersal through the Levant at ~50 ka and into northern Eurasia’ (Reyes-Centeno et al., 2014)!
Unfortunately, this new view of dual human expansion rather reads as an apologia in defense of the coastal South Asian dispersal hypothesis than that it supplies a clarification on the newly proposed second route through northern Eurasia. Indeed, Indian Indo-European and Dravidian samples ‘exhibit closer genetic and phenotypic affinity to the hypothetical second dispersal descendants (the Japanese, Aeta/Agta, and Central Asian populations)’, though it is remarkable such a detail apparently deterred the authors, declared Recent Out of Africa (ROA) adherents, only now from scoffing at the evidence.
I dare to suggest that as for now unpublished inside information on the 45 ka old Ust-Ishim genome – at 42X coverage, recently announced by Svante Pääbo – from northern Eurasia (near Omsk, southwestern Siberia) may have been decisive for this sudden change of heart. Indeed, if Mal’ta Boy (MA-1, a ~24 ka old non-Mongoloid Siberian whose genome was published by Raghavan et al., 2013) had already been identified as a direct descendent of Ust-Ishim, both early modern hominines may be allocated the same Central Asian affinity, and should thus be recognized as members of the same lineage being held responsible for the replacements of the Australoid elements in India – that should have been there instead according to the “classic” Out of Africa hypothesis.
Now, the present preprint of Povysil et al. (2014) may only give a hint on this first “Australoid” dispersal phase of modern humans. The 1000 Genomes Project Phase 1 they used, simply doesn’t include the South Asian nor Oceanian genomes necessary for an analysis. However, the overall private Asian distribution curves (figs.23-25) all reveal themselves “wider” than the corresponding European distribution curves, thus besides indicating higher densities of the longest IBD segments the Asian curves also demonstrate higher densities of the smallest IBD segments. The same applies for African shared. Fig.23 shows length Asian vs. Asian/African and European vs. European/African. For Asian there is a clear bias to shorter IBD segments if they are shared with Africans and here is a peak at shorter segments. For Europeans this effect is less clear, though there still is an enrichment of short segments around 5,000 bp for African sharing.

As for the second modern human dispersal phase, by now proposed to run through northern Eurasia, the Phase 1 data analysed doesn’t include the proper samples either. East Asia, nor even Japan, isn’t a proper approximation for ancestral Northern Eurasia: so much became clear from the genetic composition of Mal’ta Boy. However, Europe probably is, since this Siberian sample shared considerable drift and ancestry with western Eurasians. Apparent early modern influences in Europe may indeed be attested by eg. the “modern” remains in Kent’s Cavern (KC4), dated by Higham et al. at 44,2- 41,5 kyr cal BP., or the pre-Aurignacian remains in Italy’s Grotta del Cavallo that at Uluzzian culture level had an estimated age of 45-43 ka cal BP (Benazzi, 2012) – both being thus of an age similar to Ust-Ishim! As mentioned before, the complete DNA sequence of the latter is forthcoming, and though ‘Neandertal DNA in the femur suggest that the Ust-Ishim man lived soon after the interbreeding, which Pääbo estimated at 50,000 to 60,000 years ago’ (Gibbons, 2014) there is no mention of Denisovan admixture – what may potentially contradict an eastern identity of the “Denisovan” peak at 12,000 bp in Europe (fig.27A) – in case we should expect any related eastern origin of this kind. At least, the low segment-length distribution of the Denisovan-like IBD segments (whose density peaks at 12,000 bp) suggests an earlier incorporation in the modern gene pool than the main body of Eurasian Neanderthal-Denisovan segments whose densities peak between 26,000 – 27,000 bp. It would be most valuable if any of those “early short” European segments could eventually be recognized in the genome of Ust-Ishim!
In other words, I would identify the first category of IBD segments – having a deconvoluted density peak at about 15,000 bp for the early “European” layer comprising Neanderthal-like, Denisovan-like and “Archaic” IBD segments – as indicative for what currently passes as “the second modern human dispersal through northern Eurasia”. However, I am not sure the private European density peaks at 12,000 for “Denisovan-like” IBD segments (fig.27A) and near 10,000 for “Archaic” IBD segments (fig.31A) should indeed be of this same category. Why, if these components have a completely different distribution in Europe and Asia. The “Archaic” portion is more significant than the Denisovan portion in both Asia and Europe (fig.10, not shown here), what might reduce European “Denisovan” to actually a mere subset of the European “Archaic” category. Such a European connotation of ancient IBD segments could be due as well to a local strain of Neanderthal that possibly inherited from another, more ancestral member of the Denisovan clade, such as the ~400,000-year-old hominine of Sima de los Huesos, Spain, whose mitochondrial DNA indicated an early split (Meyer et al., 2013). It can’t be excluded any of these events included hominines that were actually less related to the Neanderthal and Denisovan reference samples.

Could Neanderthal DNA confirm such kind of ancient local variation? According to Castellano et al. (2014) ‘genetic diversity of Neandertals was lower than that of present-day humans and that the pattern of coding variation suggests that Neandertal populations were small and isolated from one another.’ However, despite the time-gap with the Altai Neanderthal, ‘[t]he fact that the three Neandertals carry longer tracts of homozygosity and differ more from one another than presentday humans within continents further suggests that Neandertals may have been subdivided in small local populations’. Apparently, a smaller long-term effective population for Neanderthal than present-day humans didn’t prevent them from diverging locally. Actually, Neanderthal heterozygosity may vary. It’s considerably higher in the west (0.143 for El Sidrón, Spain, ~49 ka old – or up to 0.163 at 20X coverage) than in the east (0.113, Altai, ~50 ka old), Vindija at ~44 ka old being intermediate (Table S12, Castellano et al., 2014). Apart from possible dating issues, El Sidrón heterozygosity is comparable to (or higher than) Denisovan heterozygosity (0.145 at a minimum age of 48–30 kyr ago – or down to 0.131 at 20X coverage), the latter being attributed both Neanderthal and Archaic admixtures: it was ‘estimated that 17% of the Denisovan DNA was from the local Neandertals. […] Four percent of the Denisovan genome comes from yet another, more ancient, human’ (Pennisi, 2013). Likewise for Europe, inherited archaic admixture of a divergent local source through a “hybrid” variety of Neanderthal is certainly a feasible possibility. Unfortunately, there is no way to predict the physical differences of such a local variety: ‘dental remains from the Sima de los Huesos of Atapuerca, for which ages between 350,000 and 600,000 years have been proposed, already carry Neanderthal-like morphological features that are not seen in the Denisova molar’ (Reich et al., 2010), while the archaic features in the Denisovan tooth specimen may rather derive from archaic introgression (Veeramah & Hammer, 2014). However, if Neanderthals were the “carrier” hominines from where those short non-Neanderthal IBD segments introgressed, then it could be postulated these segments should be found embedded within larger trunks of Neanderthal-like segments. Were they? Again, this can’t be retrieved from the data. Still, it’s crucial for understanding the admixture process and the hominines involved to find some positional correlation between the different types of IBD segments. If no correlation exists whatsoever, the null hypothesis of modern humans being the one and only agent for hybridization between hominine (sub)species can’t be rejected, and still this result may essentially contradict paleogenomic evidence of archaic hybridization that already happened before the appearance of modern humans. Especially the smaller IBD segments that inevitably float around independently within the modern human genomes would appear to evidence a tight association with the modern human lineage as an “agent” for direct, ancient admixture. That the smallest IBD segments being shared across continental populations date back to a time before humans moved out of Africa may be valid for the African distribution, though not necessarily (or much less so) for Asian and European distributions. This has been explained above: much of the smaller shared African segments clearly follow non-African distribution patterns.

IBD-segment size is not necessarily related directly to age, though the overall distribution of each admixture event – or selective sweep – could be assumed to be it is, or should be. The African diversity of small length IBD segments, however, is more difficult to correlate to a certain time-related profile. Hence, private African density peaks at 5,000 bp for Neanderthal-like, Denisovan-like and ‘Archaic’ alike have all appearance to form a modern human evolutionary “baseline” of great time depth. However, if – as suggested by current paleogenetic evidence – homozygous family groups of low effective population sizes were the norm for archaic hominines, and to a lesser extend even for pre-Neolithic modern humans, small length IBD segments could never have formed or thrived in the variety they do nowadays. Hence, one central assumption that emerge concerning the origin of IBD segment variety is hybridization between concurrent hominine lineages rather than balanced selection of concurrent polymorphisms as a result of within group diversification. This, despite of the fact that the opposite, diversification as a function of time, was always one of the cornerstones of the Recent Out of Africa paradigm. However, the latter can’t explain local accumulations of rare tagSNVs on the chromosome. It is quite unlikely such mutations arise independently on various lineages by chance, so the number of tagSNVs on each IBD segment determines its distance from the common genotype, as well as the IBD segment’s detectability. Hochreiter at Dienekes Anthropology Blog: ‘Short segments have often many tagSNVs: e.g. 3kbp segments have 50 SNVs. We found that short segments are tagged as good as long segments, therefore the false discovery rate should not increase for short segments.’
The mere size of small IBD segments marked by such an array of clearly distinguished tagSNVs suggests an already advanced stage of DNA fragmentation by the process of chromosome cross-over throughout generations. Moreover, it suggests heterozygous interaction with DNA of a lineage that essentially lack those tagSNVs, thus in the initial stage of having an appreciable genetic distance. Still, there must be a limit in breaking up segments by cross-over before the IBD simply disappear below detection level. Also, in the same process of fragmentation small pieces of the segment might be chopped off that only contain a few tagSNV markers that thus lost its tight association with the rest of the segment. Probably this will never occur for coding base pairs, though in all other cases this process may be inevitable and found to continuously reduce the IBD segment size, or eventually even to drain the number of detectable IBD segments in store. What happens next, would these chipped off fragments that lost genetic linkage, and residuals of disintegrated segments, including tagSNVs gone astray, simply disappear in a sink hole, or instead be randomly incorporated into common segment variability? Most probably, such fragmented, unrecognizable chomps of “grinded” DNA just recombine with an alternative segment, typically the most common one. Like already asserted in my previous blog articles, this would render a big deal of eg. Neanderthal derived introgressed DNA unaccounted for by the present detection methods that all depart only from much larger units, ie. candidate introgressed sequences.
On the long term this ongoing process of fragmenting the originally quite homozygous strains of introgressed archaic DNA by cross-over thus should have had a dual effect: the reduction of introgressed segments to lower density peak values, having few fixed differences compared to the archaic reference genome; and the integration of fragmented introgressed DNA, chipped off below sequence detection level, into the main body of genome variety. Indeed, whatever their own explanation, Vernot & Akey (2014) detected 6.1X more fixed differences (FD) for the sequences they labeled as “non-introgressed” (17.3 vs. 2.8 FD/Mb) in comparison with the fixed differences between modern humans and Neanderthal for introgressed sequences. This value was claimed as uniform, while larger non-introgressed sequences having more fixed differences were considered significantly depleted of introgressed (Neanderthal) sequences. The latter could thus be instead rather the end result of an advanced state of disintegration of the introgressed sequences, and the subsequent full integration by recombination of smaller introgressed base pairs units into common genome variability.
More radical long term results might be expected with hybrid recombination of coding DNA, either increasing the effects of purifying selection against hybrid heterozygosity, or positive selection of mutated genes that possibly incorporated a recombined mixture of ancestral and derived alleles – to the effect this DNA lost its recoverable archaic correlation. Recombination shuffles the allele content between homologous chromosomes, but needs a certain degree of heterozygosity for producing new combinations of DNA. Since these processes thus are the very result of the disintegration of introgressed DNA, Sankararaman’s (2014) ‘unexpected finding’ that ‘regions with reduced Neanderthal ancestry are enriched in genes’ doesn’t necessarily imply ‘selection to remove genetic material derived from Neanderthals.’. His observation that ‘functionally important elements’ (low B) are ‘significantly correlated to low Neanderthal ancestry’ explicitly relates to the availability of low variability chunks of Neanderthal DNA exempt of any type of recombined code. Indeed, if hybrid recombination spawned new coding variants, successful or deleterious, reduction of introgressed DNA that remained in its original state, ie. without recombination, should be expected.

In conclusion, there is no reason to consider the smallest IBD segments as anything else but preserved hybrid heterozygosity, not unlike the longer segments. Rather than attesting ancient interaction that involves a modern human host population, already rife of the currently known common segments, recombination set the stage for genetic change. Increased heterozygosity by intense hybridization in between a larger quantity of ancient hominine lineages should have accelerated IBD segment size reduction, segment disintegration and recombination. Extensive African hybridization may even have preceded a possible African or non-African backflow of the known common segments that persist in modern human DNA, thus increasing variability even more by continued recombination.
The authors were right to drop earlier attempts to date the admixtures based on the length of IBD segments. Basic assumptions on neutral inheritance and genetic offset with regard to mean recombination patterns between recognizable ancestors without gene flow, can’t be met. Relative dating is equally challenging, now heterozygosity itself determines the speed of disintegration of introgressed sequences. Hybridization and hence increased heterozygosity, may be postulated as symptomatic for a certain level of modernity, though the few available ancient genomes already attest increased heterozygosity for Denisovans and some Neanderthal before the arrival of modernity, while their cultural level can’t be distinguished as inferior compared to contemporary modern humans. Could the mere profusion of hominine lineages in Africa have been the trigger for hybridization to start off, ie. early enough to explain their disproportional availability of the smallest IBD segments? For the various distribution curves, including the smallest IBD segments, to have any dating value at all, it would be most relevant to investigate geographic clines in more detail and to exclude the effects of natural selection. I reckon the distinction between statistic models and the quirks of natural selection will become clear once, as announced in the preprint, data from the other chromosomes will be included in the analysis – and hopefully at a denser grid of genome samples. Once private IBD segments on geographically shared distribution curves may be identified thus to reveal the geographic ranges of the ancestral hominines involved, this will be very helpful in recognizing the migrational patterns of the admixed populations that we all are.

Updated 1st of May, 2014: Map of sequenced hominines added and a reference to the article of Ann Gibbons on the announced genome of Ust-Ishim.


  • About the 1000 Genomes Project
  • Benazzi – The first modern Europeans, 2012, link
  • Castellano et al. – Patterns of coding variation in the complete exomes of three Neandertals, link
  • Dienekes – Sepp Hochreiter on IBD sharing between modern humans, Denisovans and Neandertals, Blog April 14, 2014, link
  • Gibbons – Oldest Homo sapiens Genome Pinpoints Neandertal Input, 2014, link
  • Higham et al. – The earliest evidence for anatomically modern humans in northwestern Europe, 2011, link
  • Hochreiter et al. – Rare Haplotypes in the Korean Population, at ASHG 2012, link
  • Hochreiter et al. – HapFABIA: Identification of very short segments of identity by descent characterized
    by rare variants in large sequencing data, 2013, link
  • Meyer – A High-Coverage Genome Sequence from an Archaic Denisovan Individual, 2012, link
  • Meyer et al. – A mitochondrial genome sequence of a hominin from Sima de los Huesos, 2013, link
  • Pennisi – More Genomes From Denisova Cave Show Mixing of Early Human Groups, 2013, link
  • Povysil et al. – Sharing of Very Short IBD Segments between Humans, Neandertals, and Denisovans, 2014, link
  • Prüfer et al. – The complete genome sequence of a Neanderthal from the Altai Mountains, 2013, link
  • Raghavan et al. – Upper Palaeolithic Siberian Genome Reveals Dual Ancestry of Native Americans, 2013, link
  • Reich et al. – Genetic history of an archaic hominin group from Denisova Cave in Siberia, 2010, link
  • Reyes-Centeno et al. – Genomic and cranial phenotype data support multiple modern human dispersals from Africa and a southern route into Asia, 2014, link
  • Sánchez-Quinto et al. – North African Populations Carry the Signature of Admixture with Neandertals, 2012, link
  • Sankararaman – The genomic landscape of Neanderthal ancestry in present-day humans, 2014, link
  • Veeramah & Hammer – The impact of whole-genome sequencing on the reconstruction of human population history, 2014, link
  • Vernot & Akey – Resurrecting Surviving Neandertal Lineages from Modern Human Genomes, 2014, link

Expanding Hybrids And The Rise Of Our Genetic Common Denominator

September 29, 2012 10 comments

With the attestation of Neanderthal and Denisova DNA in the human genome, and strong indications for the genetic contribution of also other archaic hominines previously considered ‘extinct without issue’, the simple model of prefabricated, homogenous modern humans that moved ‘out-of-Africa’ to replace the human evolutionary residue all over the world in a single blow, failed dramatically. Now, the scientific community is literally forced to pay attention to decades of accumulated counter-evidence and criticism.

Average Joe replacing Average Joe: A new genetic common denominator rises up from the earth, combining the best of all available biological elements to adapt to a new way of life. Average Joe is a Hybrid!

One issue concerns the implied range expansions of a single ‘bottlenecked’, homogenous population that extended its African habitat to entirely new environments and climates. This should have been attested by selective sweeps in the genome – but it doesn’t.

While most people assumed that the out-of-Africa expansion had been characterized by a series of adaptations to new environments leading to recurrent selective sweeps, our genome actually contains little trace of recent complete sweeps and the genetic differentiation of human population has been very progressive over time, probably without major adaptive episodes.
[…] if some introgressed genes were really advantageous, they should have spread and fixed in the human population, but […] there is no widespread signature of strong selective sweeps in Eurasia. (Alves et al., 2012)

Selective sweep can be recognized by a large reduction of genetic variation near a favorable gene on the chromosome, caused by a quick expansion within a population of the gene by natural selection. Only a few complete sweeps and near-complete sweeps could be found, ‘suggesting that there was relatively little directional adaptive evolution associated with the “origin of modern humans.” Measuring by genetic change, agriculture was many times more important than the appearance of modern humans throughout the world’ (Hawks, 2012-07-20). Does this imply that genetic change of modern humans was predominantly not the result of sudden adaptive mutations? Possibly humans acquired their genetic adaptations to their respective extant environments in a different way:

[…] there are precious few genetic changes shared by all (or even most) humans today, that are not also shared with Neandertals, Denisovans, or plausible other archaic human groups (such as archaic Africans).
That of course follows from the fact that a fraction of today’s gene pool actually comes from those ancient groups. Their variation is (by and large) human variation. (Hawks, 2012-07-20)

Apparently, there was a host of archaic hominines out there, previously considered the evolutionary ‘dead ends’ from all over the world, whose traces can still be perceived as superimposed variability in the modern human genome. That is, up to now investigation on archaic admixture is mainly focused on the differences between modern populations, that increasingly emerge as the relicts of intense ‘archaic’ hybridization processes. ‘Neandertals and Denisovans fall within the variation observed for human nuclear sequences. Thus, only few fixed differences can be identified’ (Meyer et al., 2012). This way, out of 3.2 billion sequenced Neanderthal base pairs only about 600 Mb could be unambiguously attributed to Neanderthal introgression, what is low in comparison with Meyer’s estimation that 6.0% of the genomes of present-day Papuans derive from Denisovans. But, archaic hominines also shared a considerable genetic common denominator with modern humans, whose possible incorporation remains poorly analyzed. A variable portion of archaic DNA actually being shared with modern humans could affect the observed magnitude of introgression, but earlier assertions that Denisovans were indeed more divergent were never confirmed. Without clear traces of selective sweep, the true origin of ambiguously shared and distinctly archaic portions of the genome are impossible to tell apart. Reported examples of selective sweep remain rare:

We also identify over 100 Neandertal-derived alleles that are likely to have been the target of selection since introgression. One of these has a frequency of about 85% in Europe and overlaps CLOCK, a key gene in Circadian function in mammals. This gene has been found in other selection scans in Eurasian populations, but has never before been linked to Neandertal gene flow. (Sankararaman et al., 2012)

The circadian function refers to a chrono-biological adjustment to an external rhythm like daylight, what logically implies a genetic adaptation to the northern Neanderthal habitat with an exclusive advantage for northern populations. Such an introgressed innovation that apparently behaves like a new favorable mutation remains an exception, since hybrid incorporation and repatterning of whole chunks of introgressed DNA doesn’t require selective sweep.

These days many investigators try to reconstruct the past demography in their own way, though often the effort remains haunted by some remarkably conservative out-of-Africa assumptions. A wealth of newly published information on the subject is currently waiting for a proper interpretation to close the gap between our modern genome and the sequenced data retrieved from some of our ancestors. Conflicting perspectives often result in contradictory assertions that may be counter-intuitive and in need of reconciliation one with the other. The following investigation belongs to this category:

Science DOI: 10.1126/science.1224344

Meyer et al. – A High-Coverage Genome Sequence from an Archaic Denisovan Individual, 2012, link


We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30X) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity, indicating that genetic diversity in these archaic hominines was extremely low. It also allows tentative dating of the specimen on the basis of “missing evolution” in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.

This study has several interesting results worth mentioning: an extremely low genetic diversity of Denisova humans that can’t be observed in any modern population; the observation that Europeans have 24% less Neanderthal admixtures (“not being shared by Africans”) than Asians; and apparent indications of some hybridization event in the past, still noticeable in the chromosomes of all modern Denisovan descendents.

Low genetic diversity of Denisovans puts the asserted homogeneity of the modern human species in a new perspective. Despite all earlier speculation on an African bottleneck, designed to explain modern genetic homogeneity from a phylogenetic perspective, current genetic variability is now found to exceed the attested variability of ancient Denisovans for all modern ‘phyles’, or ethnicities:

Several methods indicate that the Denisovan hetero-zygosity is about 0.022%. This is ~20% of the heterozygosity seen in the Africans, ~26–33% of that in the Eurasians, and 36% of that in the Karitiana, a South American population with extremely low heterozygosity. Since we find no evidence for unusually long stretches of homozygosity in the Denisovan genome, this is not due to inbreeding among the immediate ancestors of the Denisovan individual. We thus conclude that genetic diversity of the population to which the Denisovan individual belonged was very low compared to present-day humans. (Meyer et al., 2012)

Nevertheless, Denisovans lack any relevant African affiliation. Their ‘phyle’ should have been separated long enough from the other branches of human evolution to have reached a genetic diversity comparable to Africans. Apparently, since this didn’t happen, genetic variability doesn’t simply translate to the age of an otherwise isolated population. Investigators may now dedicate their diligence to duplicate their calculations for a purported recent African bottleneck, and design a corresponding recent Denisovan bottleneck. Or they could just admit the geographic maxima of modern variability in Africa may rather represent archaic admixture than the age of a single human phyle.
Unfortunately, the Meyer study doesn’t mention the Neanderthal-like admixtures of Africans, except by saying that the ‘genetic contribution from Neandertal to the present-day human gene pool is present in all populations outside Africa’. It is important to keep this voluntary restriction in mind in reading their most remarkable assertion: ‘We estimate that the proportion of Neandertal ancestry in Europe is 24% lower than in eastern Asia and South America’ (Meyer et al., 2012).
This runs contrary to more detailed genetic analyses that previously revealed slightly higher levels of Neanderthal admixture in Europe. John Hawks counted derived SNP alleles of the 1000 Genomes Project being shared with the (Neanderthal) Vindija Vi33.16 genome, and found the surpluses in Europe and East Asia where rather comparable:

The Europeans average a bit more Neandertal than Asians. The within-population differences between individuals are large, and constitute noise as far as our comparisons between populations are concerned. At present, we can take as a hypothesis that Europeans have more Neandertal ancestry than Asians. If this is true, we can further guess that Europeans may have mixed with Neandertals as they moved into Europe, constituting a second process of population mixture beyond that shared by European and Asian ancestors. (Hawks, 2012-02-08 )

Unfortunately, the attested agreement between non-African and Neandertal genomes, and between Melanesian and Denisova genomes for that matter, didn’t result yet in the full identification of all specific genetic loci involved. Basically, the observed agreement was initially based on the differences between Africans and non-Africans in comparison with the archaic genome being investigated. Hence, the overall picture of archaic ‘differences’ may be distorted by shared components within the African reference group, that Meyer’s team didn’t include in their investigation and that Hawks didn’t quantify for his modern genomes that share derived SNP alleles with the (Neanderthal) Vindija Vi33.16 genome. In other words, this Neanderthal ancestry in Europe allegedly being 24% lower than Asia (according to Meyer et al.) is essentially meaningless without additional information that quantifies sharing:

My initial reaction to this difference is that it reflects the sharing of Neandertal genes in Africa. Meyer and colleagues filtered out alleles found in Africa, as a way of decreasing the effect of incomplete lineage sorting compared to introgression in their comparison. But if Africans have some gene flow from Neandertals, eliminating alleles found in Africans will create a bias in the comparison. If (as we think) some African populations have Neandertal gene flow, that probably came from West Asia or southern Europe. So as long as the present European and Asian (and Native American) samples have undergone a history of genetic drift, or if (as mentioned in the quote) they mixed with slightly different Neandertal populations, this bias will tend to make Asians look more Neandertal and Europeans less so.
Anyway, this demands further investigation. (Hawks, 2012-08-30)

Apparently, the legacy of the Out-of-Africa dogma caused Meyer et al. to take the African part for granted and just to look at the non-African part. We are lucky to have some additional information already at hand to more or less visualize how the Meyer et al. results could still be in tune with earlier results, that rather emphasized a closer match of Neanderthal admixtures with Europeans. The Austrian study of Hochreiter et al. (2012) actively incorporates the internationally shared Neanderthal and Denisova alleles in their calculations to measure the probability of uneven distribution (Fisher’s exact test) and to obtain the corresponding odds ratios, that give a symmetrical representation of the relative genetic enrichment for each type of admixture. From here on, all depends on how we perceive the human genome and what part of it we are willing to recognize as true Neanderthal or Denisova admixture, or something else.
Hochreiter’s study retrieved data from the Korean Personal Genome Project (KPGP) combined with those from the 1000-Genomes-Project:

Genotyping […] 1,131 individuals and 3.1 million single nucleotide variants (SNVs) on chromosome 1 […] identified 113,963 different rare haplotype clusters marked by tagSNVs that have a minor allele frequency of 5% or less. The rare haplotype clusters comprise 680,904 SNVs; that is 36.1% of the rare variants and 21.5% of all variants. The vast majority of 107,473 haplotype clusters contains Africans, while only 9,554 and 6,933 contain Europeans and Asians, respectively. (Hochreiter et al., 2012)

According to this data, only 6,490 (113,963 minus 107,473) of the rare haplotype clusters on chromosome 1 were exclusively non-African. The vast majority of all rare haplotypes, however, are shared with Africans one way or the other:

We characterized haplotypes by matching with archaic genomes. Haplotypes that match the Denisova or the Neandertal genome are significantly more often observed in Asians and Europeans. Interestingly, haplotypes matching the Denisova or the Neandertal genome are also found, in some cases exclusively, in Africans. Our findings indicate that the majority of rare haplotypes from chromosome 1 are ancient and are from times before humans migrated out of Africa. (Hochreiter et al., 2012)

The 9,554 and 6,933 European and Asian haplotypes thus per definition include a considerable overlap with extant African rare haplotypes. Moreover, the size of such an African overlap is proportional with the total count of shared Eurasian haplotypes. Mathematically it could be deduced that at the very least, 3,064 (ie. 9,554 minus 6,490) out of 9,554 ‘European’ haplotypes, and 443 out of 6,933 ‘Asian’ haplotypes should be also African. The maximum count of African rare haplotypes, however, that made it ‘Out-of Africa’ and are currently shared with non-Africans, remained well below 10%. Since over 90% of the African rare haplotypes are thus not shared with Neanderthals and Denisovans, in an Out-of-Africa scenario this would mean that a similar proportion of the European and Asian rare haplotypes could be expected to be non-Neanderthal and non-Denisova. Could we really rely on the ancestral origin of so many shared haplotypes? Just being shared African doesn’t make these haplotypes ancestral all of a sudden, and less without a proper quantification.
Let’s first try to quantify the potential Neanderthal admixtures a bit. Hu’s analyses of archaic segments should give an adequate peek inside the various admixtures for an educated guess:

Archaic hominin admixture with modern non-Africans was detected by genome wide analysis of Neanderthal and Denisovan individuals.
To gain better understanding in demographic and evolutionary significance of archaic hominin admixture, […] we identified 410,683 archaic segments in 909 non-African individuals with averaged segment length 83,460bp. In the genealogy of each archaic segment with Neanderthal, Denisovan, African and chimpanzee segments, 77~81% archaic segment coalesced first with Neanderthal, 4~8% coalesced first with Denisovan, and 14% coalesced first with neither (Hu et al., 2012)

Considering the above, apparently very few (or none?) of all the non-archaic haplotypes that made it out of Africa became rare. Such results, naturally, would imply one enormous problem about the construct Homo Sapiens Sapiens (HSS). Instead, the lack of rare haplotypes outside Africa that could be safely assigned unambiguously to what is generally considered the constituent forerunner of modern humans, indeed echoes much earlier claims of ancestral homogeneity. As already referred to above, population geneticist are very much acquainted with the concept of an early HSS bottleneck, since this was once designed to explain away all evidence of this kind. Hence, I appreciate the reasons why Hochreiter et al. prefer to consider the rare Denisova- and Neanderthal-like rare haplotypes in Africa ‘ancestral’, even those being exclusively African, but this preposition logically implies the existence of allegedly HSS ancestral haplotypes in Eurasia that are neither rare nor absent in Neanderthal and Denisova. Combined with the ever more unpopperian association of frequent haplotypes with HSS per definition, it has now all appearance Homo Sapiens Sapiens is nothing but the current genetic common denominator in disguise.
As for now, apparently the Neanderthal admixtures indeed account for the greater part of the Eurasian archaic components. The discovery of the Denisova component was just mere luck, and the odds are high that more archaic hominines contributed to the Eurasian admixtures. For all we know, on the eve of the transition to modern humans Europe was only inhabited by Neanderthal. However, the likelihood of additional archaic admixture in South East Asia are being widely discussed. Moreover, Hu’s results almost exclude the possibility that substantial African archaic admixtures, at least those not yet being fully incorporated in the ‘bottlenecked’ HSS population, expanded out of Africa. Altogether, it wouldn’t be farfetched to consider most of the 14% Eurasian remainder to be essentially archaic Asian. Actually, Hu’s 14% Eurasian admixtures currently unaccounted for could easily correspond to the genetic contribution of up to four Asian archaic hominines like Denisovan’s – wherever those may have existed in isolation from Denisovan-like populations that – as for now – potentially inhabited the large geographic stretch between their attested remains in the Altai mountains and their attested genetic contributions in Melanesia. Mendez et al. (2012) suggested ‘that the archaic ancestor contributing the deep lineage to Melanesians and the specimen from Denisova were members of genetically differentiated populations’, what indeed should make us wonder about the Asian location, or nature, of such unsampled hominine groups we are still missing from the record of potential archaic admixtures. Even locally admixted homo erectus have already been proposed.
Now, Hu’s fixed non-Neanderthal-non-Denisovan remainder and the ambiguous 4% apparently shared component between both sampled hominines, suggest ~40-50% ancestral overlap between Neanderthals and Denisovans for the admixtures attributed to Denisovans, against only ~4-5% ancestral overlap for Neanderthal-like admixtures. The unambiguous Denisovan component left may be considered fully Asian in origin, even though Meyer et al report an opposite effect on the current availability of Denisovan alleles all over the world:

Interestingly, we find that Denisovans share more alleles with the three populations from eastern Asia and South America (Dai, Han, and Karitiana) than with the two European populations (French and Sardinian) (Z = 5.3). However, this does not appear to be due to Denisovan gene flow into the ancestors of present-day Asians, since the excess archaic material is more closely related to Neandertals than to Denisovans (Meyer et al., 2012)

Indeed, the contribution from Denisovans is found ‘almost’ exclusively in island Southeast Asia and Oceania. Hence, Meyer’s assumption this effect is directly related to a higher proportion of archaic Neanderthal alleles in Asia justifies a ‘worse case’ scenario, where the ‘true’ Asian share could probably increase to 18-19%, against up to 81% rare archaic haplotypes that could now be tentatively attributed to essentially Eurasian Neanderthal admixtures. For now we are only interested in the counts of Neanderthal-like admixtures, so we could propose a conversion of Hochreiter’s rare haplotype counts results, that reduces the non-African count of rare haplotypes to ~5,224 Neanderthal non-African haplotypes, and that reduces the ‘non-exclusive Asian’ haplotypes to ~5,581 Neanderthal non-exclusive Asian haplotypes, while the same maximum of Hochreiter’s 9,554 haplotypes could still be assumed to be both ‘Neanderthal’ and ‘non-exclusive European’.
For sure, such an increased proportion for Neanderthal-like admixtures in Europe doesn’t make Meyer’s results more intuitive. All the contrary, Meyer’s 24% lower European contribution should make us wonder where the differences went to. Apparently, a changed proportion of non-African Neanderthal-like admixtures in Europe compared to Asia needs proportional compensation elsewhere. Unfortunately, this effect has not been illustrated in any of the studies that aim to quantify Neanderthal admixtures one way or the other.

Different scenarios based on Hochreiter’s rare haplotypes, Hu’s proportions of archaic contribution, and the following viable assumptions: Zero Eurasian and Afro-Asian components for scenario #1; Zero Eurasian and Afro-Eurasian components for scenario #2; Zero European and Afro-Eurasian components for scenario #7. The Meyer-scenarios assume a 24% lower non-African European component than Asian, while #1 and #2 were also calculated for equal shares. Lower Neanderthal-like proportions for Europe in comparison with Asian apparently imply a higher count for shared Afro-European haplotypes. The invariable high Afro-European component and less relevant Eurasian, Afro-Asian and Afro-European components are in support of an underpinning Eurasian substructure for the Neanderthal admixed population; and a massive expansion of already admixed European populations into Africa.

For a better comprehension I elaborated several possible solutions, combining the information of Hochreiter, Meyer and Hu. Hochreiter supplied values for three linear equations that involve six variables, representing the rare haplotype counts characterized as ‘exclusive European’, ‘exclusive Asian’, ‘Eurasian’, ‘Afro-Asian’, ‘Afro-European’ and ‘Afro-Eurasian’ . Meyer’s published proportion between European and Asian haplotypes introduces a fourth equation, that for comparison could be alternated with a more intuitive scenario that has non-African European and Asian rare haplotypes evenly distributed. However, a set of linear equations may only be solved (but not necessarily) if the number of equations is the same as the number of variables. Thus two variables remain undefined, what means that an array of solutions is still possible. I worked out a number of different scenarios, each based on two additional assumptions that are necessary to solve the equations. Thus, for scenario #1 I choose zero values for the Eurasian and Afro-Asian components; for scenario #2 I choose zero values for the Eurasian and Afro-Eurasian components; for scenario #3 I kept the Eurasian and Afro-European components on zero; for scenario #4 the same for the Afro-Asian and Afro-Eurasian components; for scenario #5 the Afro-European and Afro-Eurasian components were kept zero; for scenario #6 the same for the Afro-European and Afro-Asian components; and for scenario #7 zero values were assumed for the Afro-Eurasian and European component, the latter being valid only for the Meyer variant of the equations.
Scenarios #3-5 can’t be solved for natural values and scenario #6 is ambiguous. The remaining scenarios #1, #2 and #7 all show the predominance of shared Afro-European rare haplotypes, while Afro-Asian, Eurasian and Afro-Eurasian components are lower and not always required for a valid result. The effect of Meyer’s result can be illustrated for scenarios #1 and #2, where lower Neanderthal-like proportions for Europe in comparison with Asian apparently imply a higher count for shared Afro-European haplotypes and lower counts for Afro-Asian and Afro-Eurasian haplotypes.
These scenarios reveal the Afro-Asian component as fairly irrelevant, and the Afro-Eurasian component emerges as moderately weak. Only the Afro-European component remains definitely prominent in all scenarios. Remarkably, simulations that increase the Eurasian shared component are directly proportional to increases of the Afro-European component, while both are inversely proportional to the Afro-Eurasian component. This behavior supports the hypotheses that the Afro-Eurasian shared component is only moderately present; that at least the Asian Neanderthal admixtures don’t share any African origin or association in particular; and that Neanderthal haplotypes rather seem to have expanded proportionally into Africa and Asia alike from a European center. Especially the increased Afro-European component is remarkable, since an ancestral origin results problematic for rare haplogroups that feature a structural deficit in Asia.
At this stage it is impossible altogether to distinguish between haplotypes that introgressed through Neanderthal admixtures and those that may be ‘safely’ regarded ancestral to both Neanderthal and modern humans – so we should refrain from doing so beforehand. How ancestral the shared African haplotypes could possibly be? African substructure is no longer viable as a major explanation of Neanderthal admixtures in Eurasia. Actually, African substructure was already contradictory with the earlier Out-of-Africa bottleneck-and-homogeneity paradigms, and an additional west-to-east substructure to explain essentially different admixture patterns for Europe and Asia, is even less conceivable. Instead, ‘recent admixture with Neanderthals accounts for the greater similarity of Neanderthals to non-Africans than Africans’ (Yang et al., 2012). Less exclusive scenarios, that allow for early admixture events in the ancient Near Eastern contact zone, aren’t any less problematic for the discrepancy and leave the much lower Afro-Asian component without explanation. The most progressive and intuitive Out-of-Africa scenario, that considers the predominantly European distribution of Neanderthal haplotypes and predicts an increased admixture rate in Europe, now results falsified by this closer examination of Meyer’s 24% lower European rate. Apparently, the current distribution of admixtures only appeared to be in favor of any overall Out-of-Africa framework. The apparent lack of shared Afro-Asian haplotypes doesn’t indicate an African route for Asian admixtures, nor does the low count of shared Afro-Eurasian haplotypes advocate the importance of an ancestral component. Instead, an underpinning West-East dichotomy or Eurasian substructure already in place for the Neanderthal population before the attested admixture has already been proposed as a valid explanation:

Europeans and Asians could show distinct components of Neanderthal admixture if they had admixed with European and central Asian Neanderthals, respectively (Alves et al., 201)

The Afro-European shared haplotypes can’t be older than the long term genetic differentiation of Eurasian Neanderthals, what adds up to the already expounded rejection of African substructure in a recent Out-of-Africa scenario. A better explanation may be found in a massive expansion (or ‘backmigration’) of European populations into Africa, and a corresponding submersal of almost their full share of Neanderthal admixtures inside Africa subsequent to some late-Neanderthal admixture event.
Now the falsification of an important shared ancestral compenent in the African count of rare haplotypes becomes evident, Hochreiter’s data, reporting that ‘haplotypes matching the Denisova or the Neandertal genome are also found, in some cases exclusively, in Africans’, may be viewed in an entirely new perspective. If introgression of Denisovan admixtures was part of a rather ancient gene flow, albeit considerably younger than the Eurasian Neanderthal differentiation still noticeable in the strongly regionalized Neanderthal admixtures, some Denisovan alleles could have reached Africa contemporaneously with the ‘other’ archaic admixtures that arrived there through the European route, as displayed by the calculated haplotypes pattern above. Especially the world-wide distribution of shared Neanderthal-Denisova alleles raises some questions into this direction.
More detailed analysis on the immune gene OAS1, involved in ‘Denisovan’ introgression, revealed this gene was embedded in a very divergent string of DNA, referred at as the ‘deep lineage’ haplotype. Its divergence from all the other extant OAS1-related haplotypes was strong enough to exhibit the signature of archaic introgression, what means the haplotype ‘may have introgressed into the common ancestor of Denisova and Melanesians via admixture with an unsampled hominin group, such as Homo erectus’ (Mendez et al., 2012). The haplotype resembles the Denisovan haplotype ‘with the exception of one site (position 30504), at which the extant human carries the derived C and the Denisova specimen carries the ancestral T’, but even more striking is the current homogeneity of the deep lineage:

Broadly distributed throughout Melanesia, the deep lineage exhibits very low intraallelic diversity […], with an estimated TMRCA of ~25 kya (Mendez et al, 2012)

The attested Denisovan fossils in the Altai mountains had a slightly more ‘ancestral’ version of the gene, thus being different from the extant ‘deep lineage’. Actually, this unique signature boils down to a single hybridization event for this haplotype that involved one ancestral parent not unlike, but slightly different from the sampled specimen of Denisova Cave. Also Meyer’s observation that ‘Papuans share more alleles with the Denisovan genome on the autosomes than on the X chromosome’ and that eg. on chromosome 11 Denisovan ancestry is estimated to be lower in Papuans than in East Eurasians, corroborate to this hypothesis:

[…] there is significant variability in Denisovan ancestry proportion compared with the genome-wide average not just on chromosome X, but also on individual autosomes that have estimates that are also lower (or higher) than the genomewide average. (Meyer et al., 2012 sup)

Unfortunately, despite the negative evidence accumulated by Meyer et al. in their supplement against their own sex-biased modern population-history pet theories, their main article stopped short of dwelling on far more interesting factors such as hybrid chromosome repatterning that include ‘natural selection against hybrid incompatibility alleles, which are known to be concentrated on chromosome X’ and a marked uneven distribution of Denisovan ancestry also in the autosomes.

With hybrids, crossover events tend to compromise lineage specific regulatory regions on the chromosomes. Only favorable repatterning of the hybrid chromosomes results in viable offspring.

The disproportionate absence of Denisovan admixtures on the X chromosome virtually excludes a sex-biased demographic history in Oceania as an explanation and indeed, in their supplement Meyer et al. elaborated a potential rejection on logical grounds: also migrating males bring in their share of X chromosomes, so this way it can’t just disappear. A removal of Denisovan chromosome X by natural selection after the gene flow can be excluded as well: selection acting on genomic functional elements can be detected by its indirect effects on population diversity at linked neutral sites (McVickers et al., 2009), but Meyer’s team was right that they couldn’t establish that archaic ancestry was affected by the proximity to genes. However, natural selection against hybrid incompatibility alleles is still a poorly understood process – and especially if considered applicable just to the protein coding genes that constitute only about 3 percent of the human genome. This year the ENCODE Project Consortium confirmed actually over 80% of the genome to be involved in biochemical functions, in particular outside of the protein-coding regions. Genetic viability is most of all determined by the proper regulation of gene expression. Hence, much of the genome is considered constrained by biological constraints against evolutionary change. Of interest are the ‘large number of elements without mammalian constraint, between 17% and 90% for transcription-factor-binding regions as well as DHSs and FAIRE regions’ (Dunham et al., 2012), referring to regions linked to regulatory functions. But even here, the autors hold that depressed derived allele frequencies indicate ‘an appreciable proportion of the unconstrained elements are lineage-specific elements required for organismal function, consistent with long-standing views of recent evolution’.
It should be obvious that nature can’t expect much viable offspring from a fusion of gametes that brings together lineage specific regulatory regions in a random fashion. The deleterious effects of random hybrid recombination appear to be inversely proportional to chromosome crossover events during meiosis, that normally happens once for each generation. First generation hybrid offspring typically has enough directly inherited consistency of their regulatory regions on their genome left for being viable. But next generation chromosome crossover may already affect the regulatory processes of the haploid gametes being produced by meiosis. Initially, this seriously affects fertility and only the sheer scale of gamete production may compensate for the high probability of next-generation hybrid malfunction. This close relation between hybrid viability and a limited array of favorable crossover events, that shouldn’t compromise the regulatory functionality of the hybrid genome, apparently resulted also in a marked variability of ancestry proportions for each chromosome across the genome of Denisovan admixed populations.
For hybrids, selective processes are more efficient when directed at regulatory viability just before and during conception. Post-natal fitness, on the other hand, is most of all based on the ‘proven technology’ of coding genes whose selective advantage and usefulness were already attested in the parent species. Natural selection based on the success of coding genes thus may have been of less importance in recent hominine evolution than could be expected for the profound genetic change modern humans apparently went through. This detail can indeed be confirmed in the modern genome by the above mentioned lack of genetic sweep, despite important repatterning and recent genetic innovation due exactly to the occurrence of abundant hybridization in recent human evolution.
For the moment this issue should be considered isolated from the origin of the shared Neanderthal-Denisovan haplotypes, especially since this portion was already in place for the sampled Neanderthal and Denisovan specimen. Tentatively, this shared portion could be attributed to an earlier ‘bi-directional’ gene flow, leaving the specific Denisovan admixtures in Melanesia apparently to a subsequent hybridization event that only seems to have affected modern populations. The proposal above of a single hybridization event virtually excludes a scenario where the hybrid population could be considered firmly rooted in a local archaic population. Naturally, this runs counter to an array of earlier proposals that rather link Denisovan admixture events with a wide geographic range of Denisovan hominine presence between the Altai mountains and SE Asia (Reich); with different places during the migration of modern humans (Rasmussen); with distinct Denisovan admixture events in Oceanians and East Asians (Skoglund and Jakobsson); or with a process of continuous admixture where migration routes overlap with archaic hominine ranges (Currat and Excoffier).
However, a single late-Denisovan hybridization event doesn’t suffice as an exclusive scenario in the light of new evidence that posits Denisova Cave as a hotbed of Neanderthal contact. Abundant remains of Neanderthal were found nearby the cave:

The Chagyrskaya 6 mandible […] allows us now to link this material morphologically as well to the Neanderthals in Western Eurasia. Several questions remain: the timing and extent of Neanderthal expansion into the Altai, and especially the potential coexistence and interaction between Neanderthals and Denisovans. Based on availabe dates, the Neanderthals in Okladnikov cave and the possibly slightly earlier Chagyrskaya remains overlap with the wide range of dates for Layer 11 of Denisova cave. (Viola et al., 2012)

Both species even shared the same cave:

we have determined a high-quality nuclear genome from a pedal phalanx found in Denisova Cave in 2010. We show that the pedal phalanx derived from a Neandertal and thus that Neandertals as well as Denisovans have been present in the cave. (Sawyer et al., 2012)

Extensive contacts should at least have initiated a kind of fusion between the Neanderthal and Denisovan parent species into a single population where in time, due to multiple hybridization events, the variability of introgressed DNA would have been restored and integrated, into the Neanderthal genetic heritage and vice-versa. Hybrid repattering of admixed chromosomes probably wouldn’t have raised Denisovan heterozygosity beyond the elevated levels observed in modern populations, and less given the outstanding native homozygosity of the sampled Denisovans as a starting point. Indeed, the Denisovan sample has a reduced heterozygosity compared to any of the present-day humans analyzed by Meyer et al, though they reported the relative ratios of heterozygosity as fairly constant, what could be considered problematic for the assumption of archaic Neanderthal admixture already present in the shared DNA with Denisovans. However, 29 coding CCDS genes could be identified with more than one fixed non-synonymous SNC where ‘Denisova’ carries the ancestral allele, while in eight of these (OR2H1, MUC17, TNFRSF10D, MUC6, MUC5B, OR4A16, OR9G1, ERCC5), the Denisovan individual appeared heterozygous for all SNCs present in the gene. In table S44 it can be verified that 37% of this heterozygosity can be found in chromosome 11, 13% in chromosomes 6 and 7, and 11% in chromosome 8, while eleven chromosomes are homozygous for all investigated genes. Though Meyer’s team proposes this to be the result of duplications or repetitive regions, this heteromorph signature basically leaves the possibility of hybridization more than open. Since this results focus on the fixed non-synonymous SNC where Denisova carries the ancestral allele and modern humans the derived allele, the documented non-ancestral polymorphisms of Denisova even resemble modern-like admixtures.
According to Dienekes, within the group of polymorphic Eurasian SNPs there are less Denisovan than Neanderthal SNPs that are also monomorphic in the African Mbuti Pygmys. Because, actually the relation between Denisovans and Pygmy is ancestral and they share ancestral SNPs. This might reflect a lower penetration into Africa of the shared Denisovan-Neanderthal portion of archaic admixtures. If so, this could be partly due to a Denisovan origin of this shared portion, though some degree of Eurasian Neanderthal substructure may be involved as well. Interestingly, this also implies the tentative modern-like part of potentially admixtured (ie. polymorphic) SNPs in the Denisovan genome is actually less ‘African’ than the Out-of-Africa hypothesis should be happy with. If anything, despite some modern-like features, those admixtures should be assumed of eastern Neanderthal origin.

Proposed hybrid flows for various archaic components, superimposed on Denisovan related HLA-A gene distribution. Blue arrows carry Neanderthal admixtures; red-blue arrows carry mixed Neanderthal-Denisovan admixtures; the green arrow represents East African input; and brown arrows represent Asian admixture and reflux. Question marks represent unknown archaic hominines that may have contributed locally and possibly also to the common genetic denominator of modern humans.

Another modern-like feature of the potential Denisovan-Neanderthal hybridization is the above mentioned outstanding heterozygosity of chromosome 11, that almost screams for continuity with the hybrid signature of the same chromosome in Papuans, where Denisovan ancestry is strikingly low. I really wonder what could have been the impact of these hybrid changes for the now widespread Denisovan-like mtDNA segment inserted into this same chromosome 11 of modern human populations all over the world, as described in a previous post; and what could have been the link with the survival of insert-like mtDNA in the aboriginal DNA found in the Lake Mungo 3 remains (LM3) dated 40kya. But even a much lesser extend of any gradual continuation with respect to Denisova-related selective processes against hybrid incompatibility alleles would only make sense if modern populations are themselves the continuation of these same ancient hybridization processes. Apart from what this might imply for the very nature of the modern genome in general, we could at least incorporate this signature of a continuous hybridization process, that tentatively links the Altai Mountains with Oceania, in what we know about the current distribution of Denisovan admixtures. A northern route around the SE Asiatic habitat of probably very different archaic hominine populations, some of them possibly more erectus-like or even more habilis-like, such as Homo floresiensis (Argue et al., 2012), seems at present more likely than a straightforward direct southern route:

However, in contrast to a recent study proposing more allele sharing between Denisova and populations from southern China, such as the Dai, than with populations from northern China, such as the Han, we find less Denisovan allele sharing with the Dai than with the Han (Meyer et al., 2012)

Current evidence even seems to favor a specific Korean route before turning south along the Chinese coasts down to Oceania:

The enrichment of Neandertal haplotypes in Koreans (odds ratio 10.6 of Fisher’s exact test) is not as high as for Han Chinese from Beijing, Han Chinese from South, and Japanese (odds ratios 23.9, 19.1, 22.7 of Fisher’s exact test) – see also Figure 7. In contrast to these results, the enrichment of Denisova haplotypes in Koreans (odds ratio 36.7 of Fisher’s exact test) is is higher than for Han Chinese from Beijing, Han Chinese from South, and Japanese (odds ratios 7.6, 6.9, 7.0 of Fisher’s exact test) (hochreiter et al., 2012)

It has been suggested that ancient HLA-A genes of the primate immune system only survived on human chromosome 6 by balanced selection in the Denisovan lineage. Hence, the current geographical distribution of this genes is often taken as indicative for the wherabouts of Denisovan admixed descendents. As you can see on the attached map, the hybrid Denisovan trail described above corresponds fairly well with this view, except for Yunnan and Tibet where possible Denisovan-like admixtures are largely below detection level and certainly not derived from Melanesian arrivals. It can’t be excluded that here we may find the root origin of the archaic population whose remains were so far attested only in Denisova Cave. Interestingly, this hypothetized ultimate origin of the archaic Denisovan population is adjacent to Indo-China, where hominine evolution may have been as old and divergent as in Africa.
Thus, it becomes ever more difficult to identify with, or deny descendance of a particular hominine branch. Recent human evolution is like a snowball rolling down the hill. What we are is just everything what came down from the hill, and what didn’t stop rolling. We may question our ability to really take a turn since for all we know the ball just gathers more snow and increases momentum. We can’t even say our trail downhill was human all the way, or where it started, or define what sets the participants apart from everything else around it. But here we are, something completely new on the face of the earth. And most of it, we have in common.


  • Adcock et al. – Mitochondrial DNA sequences in ancient Australians: Implications for modern human origins, 2001, link
  • Alves et al. – Genomic Data Reveal a Complex Making of Humans, 2012, link
  • Argue et al. – An hypothesis for the phylogenetic position of Homo floresiensis, European Society for the study of Human Evolution 2012 meeting, link
  • Dienekes – A surprising link between Africans and Denisovans, Blog September 27, 2012, link
  • Dunham et al. – An integrated encyclopedia of DNA elements in the human genome, 2012, The ENCODE Project Consortium, link; Online review Universität Heidelberg: Allegedly Useless Parts of the Human Genome Fulfil Regulatory Tasks, 6 September 2012, link
  • Cox et al. – Testing for Archaic Hominin Admixture on the X Chromosome: Model Likelihoods for the Modern Human RRM2P4 Region From Summaries of Genealogical Topology Under the Structured Coalescent, 2008, link
  • Curnoe et al. – Human Remains from the Pleistocene-Holocene Transition of Southwest China Suggest a Complex Evolutionary History for East Asians, 2012, link
  • Hawks – Denisova at high coverage, Blog 2012-08-30, link
  • Hawks – Which population in the 1000 Genomes Project samples has the most Neandertal similarity?, Blog 2012-02-08, link
  • Hawks – Modern humans in with a whimper, Blog 2012-07-20, link
  • Hochreiter et al. – Rare Haplotypes in the Korean Population, at ASHG 2012, link
  • Hu et al. – Analysis of contributions of archaic genome and their functions in modern non-Africans, at ASHG 2012
  • McVicker et al. – Widespread Genomic Signatures of Natural Selection in Hominid Evolution, 2009, link
  • Mendez et al. – Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations, 2012, link, or try here
  • Meyer et al. – A High-Coverage Genome Sequence from an Archaic Denisovan Individual, 2012, link, supplement
  • Sankararaman et al. – A genomewide map of Neandertal ancestry in modern humans, at ASHG 2012
  • Sawyer et al. – Neandertal and Denisovan Genomes from the Altai, European Society for the study of Human Evolution 2012 meeting, link
  • Scally et al. – Revising the human mutation rate: implications for understanding human evolution, 2012, link
  • Viola et al. – A Neanderthal mandible fragment from Chagyrskaya Cave (Altai Mountains, Russian Federation), European Society for the study of Human Evolution 2012 meeting, link
  • Yang et al. – Ancient Structure in Africa Unlikely to Explain Neanderthal and Non-African Genetic Similarity, 2012, link
  • Yotova et al. – An X-linked haplotype of Neandertal origin is present among all non-African populations, 2011, link

The Hybrid-Driven Evolution of Hominids

November 27, 2011 5 comments

The acceptance of hybridization processes in the origin of species already came much closer with fossil DNA analyses and more detailed comparisons with extant organisms. For humans the strong suggestion of genetic ‘admixtures’, already claimed in various genetic studies dealing with Neanderthal and Denisova hominines, is reinforced by new investigations that now even start to penetrate the holiest of Out of Africa strongholds, that is Africa. This is no longer about a select set of single genes whose implications for origin and whereabouts could be happily reduced, but about entire sequences of diverging genome ‘regions with unusual patterns of genetic variation’: new results reveal the survival in African genes of ‘an archaic population that split from the ancestors of anatomically modern humans ~700 kya.’ (Hammer et al., 2011). Being much more than a mere warning against obsolete paradigms, this should already give us a valuable insight in what happened within the human species at a supra-regional level.

Improved distribution map of Denisova alleles, at SNPs where Denisova is different from chimpanzee and Neandertal. There is an appreciable match with A*1101 HLA alleles

In Africa the introgression event of ‘archaic’ humans was claimed to have happened about 35kya, recent enough for not spoiling the Recent Out of Africa theory altogether. So now we are required to believe that homo sapiens interbred first in Eurasia (and the north of Africa) and only afterwards with their closest African neighbors? A patched “Recent Out of Africa” scenario would now ‘predicate’ that Homo Sapiens quickly replaced much older hominines anywhere but in Sub-Saharan Africa. However, mere reluctance to believe otherwise may eventually prove futile:

I bet that a few years from now, we will look with amazement at the naivete of the passing Out of Africa orthodoxy that bundled all Africans into an amorphous category of “our ancestors in Africa”. It is also becoming clearer that increased African genetic variation is, at least in part, due to the continent being home to multiple deeply divergent populations that persisted, in various admixtures down to the present. (Dienekes’ blog, 2011-9-16)

The amount of new scientific publications able to shed more light on the issue is already dazzling and for sure preludes an inevitable change of paradigm:

We are only now beginning to harness the power of full human genomes for evolutionary inferences, but it is inevitable that a new theory of human origins will appear that will reconcile the different and conflicting lines of evidence. That theory must take into account latent admixture as a cause of African genetic diversity, and it must also harmonize with the paleoanthropological record. (Dienekes’ blog, 2011-9-19)

Scientists already speak out openly on how the ‘vast amount of recombination information in the human genome has long been ignored or deliberately avoided in studies on human population genetic relationships’ (Xu et al., 2011). The latter now introduced a method of ‘chromosome-wide haplotype sharing’ (CHS) to reconstruct reliable phylogenies of human populations and state that instead of variation being an unbiased measure of population age, ‘the majority of the variation in CHS matrix can be attributed to recombination.’
Unfortunately, time and origin of the admixtures remain hard to quantify. Sampled fossil hominines so far didn’t correspond to much closer modern matches in the wider geographic region. Denisova admixtures have top levels in SE Asia and Australia while traces are virtually absent in South Siberia, where of both Denisova fossils were found. Likewise, Neanderthal admixtures have top levels in East Asia and the Americas, far removed from the known European habitats of Neanderthal, where 1000 Genome Project results are at most comparable, and sowehat lower in northern Europe. In his blog John Hawks suggests population history and natural selection may have caused this distorted picture, while much of the purported evidence for local continuity of Denisova genes may be of a quite different magnitude. Certain HLA genes, part of the modern human immune system also found in the genomes of Denisova and Neanderthal hominines, would have been straightforward evidence for introgression and local continuity – if only those genes didn’t derive from much older primate genes. Balanced natural selection could have been an alternative to account for the survival of ancient genes, supplying false positives for the survival of a select set of Denisova genes. Still, the current geographical distribution of the HLA-A*11 variety found in Denisova, by Parham, concurred remarkably with that of other derived Denisova alleles, published afterwards:

[…] we found that East Asian populations, particularly Southeast Asian populations, had, on average, a greater frequency of the derived Denisova allele compared with other populations (except for Oceanians) […]. (Skoglund & Jakobsson, 2011)

Since this particular HLA-A*11 variety is mostly found in Asians and never in Africans this indeed suggests introgression by interbreeding outside of Africa. True, such alleles existed already at the same position in the genomes of apes, but now with supporting evidence this detail should supply an entirely new dimension to the issue: introgression of DNA previously conserved merely on evolutionary sidelines should imply temporal extinction of the gene on the main hominine lineage!
At least, extinction is exactly what happened at a much larger scale with primate ABO blood group genes: chimpanzees so far attested for blood type A and some O, but not for B, and gorillas attested for blood type B and some O, but not for A. The ABO blood type is controlled by a single ‘ABO’ gene, for humans on the long arm of the ninth chromosome (9q34).

In the case of human ABO blood group genes, three alleles (i.e., A, B, and O alleles) have been observed, but it is known that chimpanzees have two alleles (i.e., A and O alleles). (Kitano et al., 2000)

Blood groups are inherited from both parents, that may be homozygous for one or heterozygous for two classes. This means that despite being ancient, any of the groups could become extinct once an epidemic demands a strong response that involves unbalanced selection of another allele. Eg., blood group O was observed to have an advantage against malaria, leading to the hypothesis that ‘selective pressure imposed by malaria may contribute to the variable global distribution of ABO blood groups in the human population.’ (Rowe et al., 2007). Since malaria is strongly related to warm wetland habitats, this may be an example of an ancient immune system whose usefulness and survival may be a matter of habitat. If so, then speciation – that implies a formative stage of isolation within a new habitat – also implies an increased risk. Among the great apes only orangutan attested all three types, suggesting that extinction of immune system-related alleles may indeed have happened more often. Reintroduction of ancient genes that became lost may be an almost impossible affair without subsequent introgression by hybridization. Nowadays such potential hybridization partners may be hard to find for chimps or gorillas, probably characterizing the evolutionary costs of their speciation. However, for the human lineage hybridization remained a possibility with species or subspecies that co-evolved within a wide range of different habitats, where different survival patterns and demands had their unique effect on local adaptations, ie. including the immune system! In summary, balancing selection may play a trick on us here, but the evidence is highly suggestive of the deep time depths involved for the genetic divergence achieved before introgression.
Equally remarkable was the absence of Denisova genes being confirmed for Central and South Asia, closer to the fossil origin. The route of Denisova genes to SE Asia must have led through East Asia, but the replacement in Central Asia by other rare varieties of HLA raises even more questions. Such as the origin of the Central Asiatic allele HLA-B*73, not attested in Denisovans, but in modern humans always associated with the ‘Denisovan’ HLA-C*15 antigen, thus suggesting either an hitherto unknown presence in other Denisovans, or a hybrid neighbor.
A recently deciphered genome “from a 100-year-old lock of hair donated by an Aboriginal man” confirmed that despite long time isolation, their proportion of Neanderthal segments match that observed in European and Asian sequences. This Neanderthal component may have been available when the ‘aboriginal Australians split from the ancestral Eurasian population 62,000 to 75,000 years B.P.’ (Rasmussen et al., 2011). However, even though according to the latest insights East Asians are considered significantly closer to Denisova relative to Neandertal, the morphology of aboriginals is rather related to archaic populations and fossils in the wider region of South and South East Asia:

This study has shown that Southeast Asia was settled by modern humans in multiple waves: One wave contributed the ancestors of present-day Onge [Andaman Islands], Jehai [Malaysia], Mamanwa [Philippines], New Guineans, and Australians (some of whom admixed with Denisovans)
we considered the possibility that the secondary gene-flow event into the ancestors of Australians and New Guineans came from relatives of Chinese (CHB) rather than western Negritos such as the Onge. (Reich et al., 2011)

Indeed the Denisova admixtures follow a rather geographic pattern, being present in eastern Indonesia and among the Mamanwa ‘Negritos’, but virtually absent in the ‘Negritos’ of Malaysia and the Andaman Islands. Most probably the aboriginals, where tests revealed ‘slightly less allele sharing than observed for Papuans’ – got the component from their closest geographic neighbors, thus flouting the Out of Africa model and increasing the mystery of the timing and origin of Denisova intrusion.

[…] it is becoming increasingly difficult to imagine a structure model that can fully explain the complex pattern of archaic ancestry in non-Africans without invoking any restricted admixture events with archaic humans. Instead, we suggest that direct gene flow from archaic populations is the most likely explanation for the shared genetic ancestry between East Asian populations and the Denisova genome (Skoglund & Jakobsson, 2011)

Likewise, somewhat lower averages of the Neanderthal component in their previous (esp. north-) European heartlands and unpublished reports of unrelated archaic admixtures both in Europe and South Asia should make us weary about the significance of current geography for the origin question at all. If dislocation of genetic affinity with fossil samples defines a tendency, we can’t even be sure the African archaic admixtures mentioned above indeed derive from an African core region. However, Wall et al. (HGV2011) reported that part of the genetic regions on the human genome ‘were found in the genomes of both sub-Saharan African and non-African populations’. At least some of the archaic admixture became international, not unlike we already known of the V and M haplotypes of gene ASAH1, coalescent-time depth 2.4 million years ago, that ended up evenly dispersed around the world. The mere age of the African archaic introgressive DNA currently under investigation vastly exceeds the age of Neanderthal and Denisova, even that of their (and our) common ancestor Homo heidelbergensis, an extinct species of the genus Homo that lived between 600 and 400 thousand years ago. This seems to be ever less in agreement with the traditional biological species concept (BSC) that tends to relate speciation with highly effective reproductive isolation, and questions the very nature of the human speciation process over time.
Actually, current biology textbooks don’t hesitate anymore to supply ‘prohibitive’ answers, that simply urge to be applied to the human species:

Typically, gene flow occurs between the different populations of a species. This ongoing exchange of alleles tend to hold the population together genetically. (Campbell Biology, ninth edition, 2011)

Speciation still occurs by the evolution of reproductive isolation, but ‘there are many pairs of species that are morphologically and ecologically distinct, and yet gene flow occurs between them.’ An example is the grizzly bear and the polar bear, that despite occasional natural hybridization remain distinct. ‘This observation has led some researchers to argue that the biological species concept overemphasizes gene flow and downplays the role of natural selection.’ (Campbell Biology, 2011). Some other species appear to be actually fully hybrid, like the Tiger Swallowtail Butterfly (appalachiensis): ‘Inter-specific hybridization is widespread in nature and may have important consequences in evolution, from the transfer of adaptive alleles between species to the formation of hybrid species’ (Kunte et al., 2011). According to the investigators the ‘evolution and persistence of appalachiensis in contact with its parental species suggests that hybridization among animals may result in selectively favored hybrid species that contribute to biodiversity.’ Hence, this example exposes a ‘potential role for natural selection in the origin and maintenance of hybrid species.’
Indeed, ‘hybridization is not always a dead end, as the BSC might suggest, but a potential source of new array of hybrids (hybrid swarms) that may establish themselves, eventually in new ecotone habitats, and evolve as new species. One common feature of the process that accompanies hybridization is the rapidity of genome repatterning which is hardly explained by the conventional mutation and recombination rates. Rather, transposition bursts ensuing hybridization suggest their involvement in these rapid genome reorganizations.’ (Fontdevila, 2005)
The risk of speciation may be genetic isolation and inbreeding, the risk of illimited hybridization of subspecies is the potential loss of local environmental adaptations, like the white color of polar bears following the example above. Over time, reproductive barriers may be either reinforced or weakened. In the latter case, hybridization may eventually lead to ‘the fusion of the parent species’ gene pool and a loss of species.’ (Campbell Biology, ninth edition, 2011)
As such, there is no specific reason why mere biology wouldn’t supply answers for the apparently torturous evolution of the human species, or for the sudden appearance of African apes:

In a punctuated pattern, new species change most as they branch from a parent species and then change little for the rest of their existence. (Campbell Biology, 2011)

Both patterns of how species evolve have been observed for the radiation of the mammals over the last 165-million-year. The majority of mammal species, including even the most speciose orders (Rodentia and Chiroptera), experienced an explosive 10-52 fold increase in the rate of evolution only during their initial formation up to the common ancestor. Stable rates of evolution of species, however diverse, were recorded almost everywhere else.

These results necessarily decouple morphological diversification from speciation and suggest that the processes that give rise to the morphological diversity of a class of animals are far more free to vary than previously considered. Niches do not seem to fill up, and diversity seems to arise whenever, wherever and at whatever rate it is advantageous. (Venditti et al., 2011)

The sudden appearance of chimps and also gorilla in the fossil record may indicate their speciation occurred relatively rapidly, when they occupied and then filled their ecological niches. Over the wider humanoid lineage things may be different:

For species whose fossils changed more gradually […] it is likely that speciation in such groups occurred relatively slowly, perhaps taking millions of years. (Campbell Biology, 2011)

How literally we could take these ‘millions of years’ for the lineage leading to great apes and modern man? Decades of behavioral studies resulted in the insight that apes are far more hominized than was once believed. According to Krützen et al. (2011) this already applies to the cultural plasticity of orangutan. Since this tendency to share particular behaviors in a group was also demonstrated in wild populations of chimpanzees this suggests evolutionary roots in the ancestors that all great apes share with humans. How realistic this would be for the biological species concept, assuming orangutan diverged from our common ancestor 15 mya, or more? Many hominizing tendencies, like the slowing down of juvenile growth, could develop for all humanoid lineages well after such divergence dates. Or would hominized behavior invoke exactly the opposite of BSC with the first onset of organizing a beneficial habitat to the temporarily impaired, like hybrids? Hominized groups could offer better opportunities to overcome some hybrid-related barriers such as lower fitness and fertility. Better survival opportunities would enhance the possibility that hybrid-related genome repatterning could stabilize recombination by endogenous purifying selection over a longer period, maybe several generations, to the effect that both fitness and fertility could be restored over time by the natural resilience of genetic processes. Indeed, if hybridization may explain parallel developments among humans and great apes, we could postulate genetic exchange between diverging ape lineages spanning millions of years.
The laboratory or Reich in Boston has a record in the study of hybrid-driven evolution, and substantiated hybridization already in 2006 for the hominine lineage. What the team called a ‘realistic upper bound of < 17 Mya for human-orangutan genome divergence' resulted in a common ancestor with chimpanzee less than 5.4 mya, including a considerable period of mutual hybridization:

Most strikingly, chromosome X shows an extremely young genetic divergence time, close to the genome minimum along nearly its entire length. These unexpected features would be explained if the human and chimpanzee lineages initially diverged, then later exchanged genes before separating permanently. (Patterson et al., 2006)

The study concluded that introgression of chimp-like DNA in the human lineage, or the other way round, happened after about 1,2 million years of divergence. This year’s ICHG meeting a team of accredited scientists led by J. X. Sun presented a tight refinement of previous date estimates:

Human-chimpanzee speciation is estimated to be 3.92-5.91 Mya, challenging views of the Toumaï fossil [Sahelanthropus] as dating to >6.8 Mya and being on the hominin lineage since the final separation of humans and chimpanzees. (Sun et al., 2011)

Indeed, despite initial efforts to link this transitional period of hybridization with older hominines, the time span of Ardipithecus would make a much better match, and more so due to the immediate succession of Australopithecus: this hominine ancestor complied even less to the more chimpanzee-like anatomy commonly expected with the genetic similarity of humans and chimps:

In an assessment of fossils from Kanapoi (3.9-4.2 Myr ago), the anagenetic series Ar. ramidus, Au. anamensis and Au. afarensis has been hypothesized. The evidence reported here from the Afar Rift constitutes a strong test from a single stratigraphic succession that fails to falsify this hypothesis (White et al., 2006)

The cited evidence of introgression revolted against traditional phylogeny, but the proposal adhered to the established view: one single lineage up to a common ancestor of humans and chimps. Supportive molecular evidence and dating is commonly cited, but the devil is in the details:

Although chimpanzees are our closest relatives, there are many loci at which humans and gorillas (or chimpanzees and gorillas) are the most closely related; we estimate that this is the case over about 18–29% of the genome (Patterson et all, 2006 Supp.)

Likewise, ‘data based on morphological analyses and with the data based on mitochondrial ribosomal genes […] suggest a closer relationship between gorilla and chimpanzee’ (Rasheed et al., 1991).
A much longer history of shared ‘hominizing’ evolution that encompass all great apes may be implied, and more so by additional inconsistencies in the order African apes are supposed to have diverged from the lineage leading to modern humans:

The late-divergence hypothesis […] specifically focuses on the divergence between humans and the ape, emphasizing that there were two different divergence points in the evolution of recent hominoids. (Wolpoff, 1982)

Thin enamel, knuckle walking and specialized feet for grasping are just a few shared features of African apes that are difficult to reconcile with two separate speciation events from an otherwise more hominine fossil record. For instance, despite Begun’s certainty on the knuckle-walking habits of our earliest common hominid ancestors, this remains utterly hypothetical – and utterly unsuported by more complete and recent fossils like A. sediba, and even Ardipithecus had not evolved the hands and wrists of a knuckle-walker. Homoplasty among different African apes that feature knuckle-walking is equally unsupported:

[This study] does not support the hypothesis of a knuckle-walking complex, nor does it support the contention that knuckle-walking could have been easily evolved independently in chimpanzees and gorillas. (Williams, 2010)

Instead, Grehan and Schwartz (2010) make a case for grouping ‘the monophyly of hominids and various Miocene–Pliocene fossil apes and orangutans into a ‘dental-hominoid clade’, with the African apes as a sister clade along with the putative [hominines] Ardipithecus and Sahelanthropus.’ In this view only the early hominine Orrorin could link the ‘dental-hominoid-clade’ to humans, thus suggesting a smooth transition along this lineage to hominids, but leaving the close family relationship with African apes unresolved.

Orrorin is […] already quite distinct morphologically from the African Great Apes (Gorillidae). This indicates a divergence between Hominidae and Gorillidae that dates back to a substantial period prior to 6 Ma, and we estimate about 8-7 Ma for this event. If so, then the discovery of Orrorin refutes all hypotheses in which humans diverged from apes later than 7 Ma, including most of the recent estimates by molecular biologists who tend to think of the divergence as having taken place later than 5 Ma, and even as recently as 2.5 Ma. (Martin Pickford, 2001)

Molecular evidence favors a close relation with African apes, but a much tighter morphological affiliation of the human lineage with orangutan can be observed:

[…] in addition to the development of low-cusped cheek teeth and thick molar enamel, humans shared a significant number of derived features uniquely with the orangutan (e.g. in reproductive physiology (gestation length, estriol levels, absence of estrus), degree of cerebral asymmetries, fetal adrenal zone size, lack of keratinized ischial callosities, mammary gland separation, hair length, incisive foramen number] (Schultz, 2004)

Indeed, the duration of the menstrual cycle varies with species; about 29 days in orangutans, about 30 days in gorillas and about 37 days in chimpanzees. Only the genus Hoolock (previously Bunopithecus), probably the most basal member of the lesser apes (gibbons), match human females ‘precisely’ – except for a considerable variability – in having an average menstrual cycle of 28 days (Geissmann et al., 2009). Cytogenetic evidence pleads for a shared development that considerably exceeds a basal relationship with great apes but unfortunately, so far gibbons are generally dismissed as even more distant from humans than orangutan.
Grehan (2006) expanded on this paradox by noting that ‘the orangutan relationship is supported by about 28 well-supported characters, and it is also corroborated by the presence of orangutan-related features in early hominids’ such as a thickened posterior palate and anterior zygomatic roots. We could add characteristics of their close fossil relatives such as dental structure, thick enamel, shoulder blade structure, thick posterior palate, single incisive foramen.

Comparative morphology supports a unique common ancestry for humans and orangutans as the only phylogenetic theory with substantial corroborated evidence. Even supporters of a unique common ancestry for humans and chimpanzees collectively support more (26) orangutan-related human characters than they do for chimpanzee-related human characters (Grehan, 2006)

Despite the impressive list of unique correlations shared between the human lineage and orangutans, the vast overall genetic distance between the species is often cited as evidence to a deep and rather straightforward phylogenetic affiliation. Genetic isolation of the orangutan lineage – according to molecular evidence between 14-17 mya (million years ago)- doesn’t help in understanding the last recorded interspecies hybridization event between ancestral humans and chimps from the ‘dental-hominoid’ point of view. In the words of Schwartz such an extended period of geneflow between widely divergent ape lineages certainly “pushes the limits of credulity” regarding the hybridization hypothesis.
For the moment I could suffice to notice that morphological and molecular evidence, that challenges the joint divergence of hominines and chimp ancestors from the ancestors of gorilla, may be explained by introgression: as in the example of hybrid polar bears, hybridization doesn’t necessarily imply the fusion of divergent evolutionary adaptive lineages. But hybridization could have complicated the hominid phylogeny beyond limits over a very long time, and even more so as the common source of adaptive radiation events towards speciation was rooted in a common ancestry that started long ago as a balanced process between evolving species.
Actually, human curiosity supplied comparable results for other species, suggesting relative time depths that correspond to what could be expected for the hybridization of diverging ape lineages:

Recent interspecific hybridizations have been well documented for the Bos and Bison species […] : zebu and ox in several tropical regions; zebu and banteng in Indonesia; taurine cattle and yak in China, Mongolia and Siberia, etc. Ox-zebu hybrids are completely fertile, while male progeny of other hybridizations are sterile. Earlier introgression events may be indicated by the anomalies in the mitochondrial phylogeny […] that are incongruent with trees of nuclear genes, AFLP fingerprints (these studies) and Y chromosomal sequence variation
Since exchange of genetic material depends on the geographical overlap of the regions inhabited by the species and their ancestors, this is consistent with the hypothesis that reticulation influenced the phylogeny of the Bovini. (Buntjer et al., 2001)

Cross-breeding of ox (genus Bos) and bison yielded fertile females and (mostly) infertile males. The same was implied by Reich, Pattison and colleges for hominine interbreeding with chimps. The fossil record already distinguishes bison in the range late Pliocene-Early Pleistocene up to 2 million years ago, while the origin of Bos (ie. cows) is contested. Their divergence is unlikely to be less than 2 million years, and possibly considerably longer:

The oldest clear evidence of Bos is the skull fragment ASB-198-1 from the middle Pleistocene (~ 0.6 – 0.8 Ma) site of Asbole (Lower Awash Valley, Ethiopia).
Although the origin of Bos has traditionally been connected with Leptobos and Bison […] we propose here a different origin, connecting the middle Pleistocene Eurasian forms of B. primigenius with the African Late Pliocene and early Pleistocene large size member of the tribe Bovini Pelorovis sensu stricto.
The Bison lineage […], based on skull anatomy, can be interpreted as resulting from anagenetic evolution of the Late Pliocene forms of Leptobos across the Plio-Pleistocene transition (~2.0 – 1.7 Ma)
The cranial anatomy of Bos, however, is highly derived as to be considered the result of a direct anagenetic evolution from any form of Leptobos. Martinez-Navarro et al., 2007)

Bison cows ordinarily conceive for the first time at 2 years of age while chimps reach their reproductive age only at 13.5 years, almost 7 times later. Accordingly, this translates to the feasibility of an extended period of geneflow for the ape lineage that may even exceed the lapse of 10 million years to bridge all genetic divergence between the common ancestor of all great apes and the reported chimp-hominine hybridization event.
As a caveat it should be noticed that fertile first generation (F-1) half-bison bulls are also registered (Wyoming Thunder being one example). This possibility increases when the bull parent already had some cattle blood, though in some cases this could not be confirmed. This observation typifies hybrid infertility as an essentially temporal evolutionary problem.

The grolar bear is a natural hybrid of grizzly bear and the polar bear. To the right the beefalo, fertile offspring of bison and cattle. Below Wyoming Thunder, a F-1 fertile bull from a male bison.

A strict phylogenetic model appears to be insufficient to reconcile genetic evidence with the origin of the human lineage from any ape clade in particular. Common biological insights on speciation suggest we should get rid of the thought that divergence, even irreversible speciation is the most natural thing to happen over time. Adaptive radiation may not be synonymous with isolation, especially in the initial period when the new phenotypes are still evolving. A re-evaluation of the entire fossil evidence would be necessary before we could even try to clarify the most controversial issues in human evolution today.
New paleontological evidence and analysis can often be relied on for correcting the phylogeny, even if molecular and morphological data turn out to be contradictory or are giving false positives. This was true respectively for whales, whose fossil ancestors confirmed their genetic affiliation with even-toed ungulates, and the Laotian rock-rat Laonastes whose genetic missing link status for New World Caviomorpha and ‘African’ Hystricognathi didn’t survive renewed scrutiny due to new fossils that revealed it as a Lazarus species of the extinct -essentially Asiatic- diatomyid taxon. Instead, so far paleontological data didn’t resolve contradictory evidence for hominids. There is an ever stronger tendency among scientists to reject the reliability of fossil evidence, and to recur to the possibilities of ‘extraordinary plasticity’.
True, mosaic evolution is considered rampant among primates, from the earliest prosimians up to modern humans, and the list of abortive evolutionary lineages towards modern primates and humans is getting ever more awesome. The ancestors of hominines must have been generalists that had still much in common with the very first anthropoids, or apes maybe as early as late Oligocene, irrespective of the evolutionary changes that were attested in the fossil record of Eurasiatic apes commonly identified as members of two clades, Dryopithecus and Sivapithecus. Unlimited plasticidity of species would open up the possibility of a thorough rejection of all current fossil evidence. Any primitive African ape could have remained in stasis for millions of years, in the middle of countless abortive lineages each well on its way to evolve into the same direction, until one ancestral species followed in their footsteps and plunged itself into an accelerated evolution towards the surviving modern African apes and hominines? and assumes African apes and humans developed from another common ancestor. In a Popperian sense this scenario can´t be falsified, since no fossils are required to meet this standard, what renders this scenario remarkably unscientific. But, could it be?
Only recently molecular evidence forced scientists to the abandon their reliance on morphological and anatomic arguments for equids, whose fossil record was once considered a textbook example of gradual, straight-line evolution. The North American evolutionary sequence from ‘Eohippus’ (Hyracotherium) to ‘Equus’, that eventually became an immigrant to the Old World, was exploited as an argument by Thomas Huxley in his defense of Darwins evolution theory. For a long time this remained one of the most widely-known examples of simple evolutionary progression, notwithstanding the few decades we already knew this ‘straight line’ was rather a bush, where even gradual transformation didn’t always apply. Regarding the once flourishing bush of species, modern equines – like humans! – were still considered a single twig. However, the scientific community was utterly unprepared for the blow this concept would receive of molecular evidence extracted from fossils. Nowadays we have compelling evidence that at least once this twig became intertwined with another.

Cladistic analysis of dental, cranial, and postcranial characters separate Hippidion and Equus into two different clades, which share the North American late Miocene Pliohippus as a common ancestor around 10 MA (Prado and Alberdi 1996).
Alternatively, MacFadden (1997) has suggested that Equus is derived from Dinohippus, and Hippidion from Pliohippus sensu lato (including Astrohippus), implying that the divergence between Dinohippus and Pliohippus occurred prior to 10 MA.
(Orlando et al., 2007)

Molecular evidence proved that the Hippidion, an extinct south american horse with some Pliohippus characteristics, was most similar with moders equids.

Hippidion is considered to be a descendant of the pliohippines, a primitive group of Miocene horses that diverged from the ancestral lineage of equines (a category including all living and extinct members of the genus Equus, such as caballine horses, hemiones, asses, and zebras) prior to 10 Ma ago […]. A recent study presented genetic data from three southern Patagonian specimens morphologically identified as Hippidion. Unexpectedly, the sequences clustered inside the genus Equus (Weinstock et al., 2005)

Hippidion differed less from caballine equids than all extant non-caballine equids (including donkeys, zebras etc.). This result inspired the team to question the deep morphological split:

The close phylogenetic relationship between Hippidion and caballine horses is in direct contrast to current paleontological models of hippidiform origins. Nevertheless, we are confident that these sequences are those of Hippidion rather than the South American caballine form E. (Amerhippus), which dispersed into South America about 1 to 1.5 Ma later than Hippidion. (Weinstock et al., 2005)

On morphological grounds, the phylogenetic separation between the lineages of Pliohippus/Hippidion and Dinohippus/Equus (modern equines) was previously estimated at 10 mya, and tentatively associated with the merychippine radiation of 15 mya. but the close genetic relationship now attested for Hippidion and caballine equids shatters such deep divergence. Equine evolution now faces the same dilemma as the human origin question, where morphology and molecular evidence are equally at odds. History repeated itself and like what happened before in paleoanthropology in the face of molecular evidence, scientific consensus rather conformed to the biological species concept and concluded that morphology was deceiving:

These data suggest that temporal and regional variation in body size and morphological and anatomic features should be considered a sign of extraordinary plasticity within each of these lineages. Such environment-driven adaptative changes would explain why the taxonomic diversity of equids has been overestimated on morphoanatomical grounds. (Orlando et al., 2007)

Another phylogeny isn’t hard to make, but even the divergence date of extant equines becomes questionable now the DNA of all three extinct American horse species was revealed to cluster specifically with cabelline horses. Genetically, the most recent common ancestor of all modern equids should have lived ‘merely’ ~5.6 mya, and still this appears inconsistent with proposals towards a single Out of America exodus event through Beringia during the glacials, at most 3 mya. Perhaps the easiest way to deal with evolutionary inconsistencies is to just forget about the need of a strict phylogenetic tree at all. For being a viable alternative to morphological continuity, hybridization processes must have been an important element in equine evolution for millions of years. Naturally, divergence dates would easily be overestimated with a last common hybrid ancestor, and easily underestimated for the species – or subspecies – that were the constituent components of the hybridization. For sure this would urge for another evolutionary model, and perhaps the identification of very different genetic signals.
It is suggested that among mammals, equines exhibit the highest rate of chromosomal evolution. Commonly considered Old World immigrants from North America, they feature a progressive ‘decrease’ of their chromosome count moving further away from Beringia: Prezewalski still has 66 chromosomes, 2 more than the domestic horse that is commonly believed to belong to the same species. Of their closest neighbors, the Asian asses, the count ‘drops’ to 56, while the African ass could preserve 62 chromosomes. Extant zebras count 46 chromosomes for the northern Grévy-zebra, 44 chromosomes for the common plains zebra and 32 for the southernmost mountain zebra. Before, maybe inspired by equivocal ideas concerning equine evolution, scientists were inclined to assume the primacy of chromosome fusion in karyotypic evolution, but:

Recent advances in cell-cycle regulation, chromosome behavior, fossil record, and phylogenetic inferences dispute that the primary direction of karyotypic evolution by sequential fusion of chromosomes is toward an arbitrary reduction in diploid number. (Kolnicki et al., 2000)

Lower chromosome counts of equids the further away from the American origin of Equus may now be attributed to conservatism, and the higher counts to ongoing change and evolution.

A key postulate of Todd’s karyotypic fission theory is the idea that in a postfissioned karyotype with a high number of acrocentric chromosomes, a trend for acrocentrics to revert to smaller mediocentrics by pericentric inversion (or centric fusion) repotentiates the karyotype for further fissions correlated with episodes of adaptive radiation directly inferable in the fossil record (Fontdevila, 2005)

For instance, the reduction-argument has been ‘turned on its phylogenetic head’ with investigations on cycads – often mistaken for palms or ferns, but only distantly related to either. The cycad fossil record dates to the early Permian, 280 mya.

Zamia is unique among cycads in that both inter- and intraspecific chromosome numbers range from 16 to 28, excluding 20 […], with varied karyotype composition
The large size of chromosomes in all cycad taxa excluding Zamiaceae […] indicates that chromosomal fission has been rare or absent in these taxa.
Molecular analysis has generated limited evidence for any chromosomal rearrangements, including chromosomal fission and pericentric inversion, as the main mechanism driving karyotypic evolution in Zamia.
(Olspon et al., 2011)

In chromosomal fission the total number of chromosome arms remains the same, ‘whereas pericentric inversion and/or hybridization of different karyotypes may either add or subtract from the total arm count’:

Pericentric inversions of the different combinations of telocentric chromosomes and/or hybridization were almost certainly involved in generating the chromosome arm numbers observed, a conclusion based on the size and number of chromosomes. Chromosome arm counts for all [Zamia] taxa in this study […] suggest that chromosomal fission, pericentric inversion, hybridization of different karyotypes and a combination of these mechanisms occurred in the evolutionary history of this genus (Olspon et al., 2011)

All corroborate to the notion that – under certain circumstances – adaptive radiation and speciation are symptomatic to chromosomal change.
The significance is obvious: ‘Chromosomal fission decreases genetic hitchhiking by severing transcentromeric linkages, allowing for direct selection on newly unlinked genes’ (Olspon). However, there must also be a drawback since in the course of evolution the number of chromosomes didn’t increase without limit. As for cycads in general, and most zamia in particular, the preferred count seems to stabilize at a low number chromosomes: ‘most early diverging cycad taxa have 2n= 16 or 18, with mostly metacentric and submetacentric chromosomes’.
Despite the exceptional features of some members of the clade, chromosomal stability and equilibrium is suggested for most cycad species. A straightforward correlation with morphological variability and stressful or widely variable habitats, that would require high levels of genetic adaptation, is falsified by the stable habitat, primitive morphology and high chromosome number found at the species Z. roezlii that inhabits the Colombian rainforest. The high age of the clade may be important evidence that fission may also be reminiscent of adaptive radiation events in the past. Over time this may be compensated by a corresponding reversal of the chromosome count by fusion. At least this is indicated in basal vertebrates, where ‘some ancestral segments were fused prior to the divergence of salamanders and anurans’ (Voss et al, 2011).
A pattern of chromosomal equilibrium may be observed in cichlid fishes:

Perciformes represents the largest order of vertebrates with approximately 9.300 species. It includes more than 3.000 species of the family Cichlidae [1,2] that is one of the most species-rich families of vertebrates
Phylogenetic reconstructions are consistent with cichlid origins prior to Gondwanan landmass fragmentation 121-165 MYA
The karyotype formula 2n = 48 st/a [subtelo/acrocentric] elements is characteristic of Perciformes
Although there is extensive variation in the karyotypes of cichlid fishes (from 2n = 32 to 2n = 60 chromosomes), the modal chromosome number for South American species was 2n = 48 and the modal number for the African ones was 2n = 44.
Pericentric inversions are thought to be the main mechanism contributing to changes in the basal chromosome arm size of Perciformes. Other mechanisms of
chromosomal rearrangement and translocation probably have contributed to the karyotypic diversification of South American cichlids. The chromosome number variation observed in some species suggests that events of chromosomal translocation followed by chromosome fission and fusion were also involved.
(Poletto et al., 2010)

Like already observed with horses, increased chromosome counts rather represent an evolutionary stage of change rather than a new equilibrium. Kolnicki’s karyotypic fission theory that ‘ posits that all mediocentric chromosomes simultaneously fission’ is just a variation of the theme:

That chromosomal diversity of such distinct taxa is explicable by fission implies this mode of animal evolution is important.
Increases up to nearly doubling of smaller derivative chromosomes throughout the Cenozoic underlie adaptive radiations, at least in artiodactyls, carnivores, lemurs, Old World monkeys, and apes. (Kolnicki, 2000)

This is not the place to discuss the general applicability of Kolnicki-type processes, except that Müller’s hypothesized ancestor of the lesser apes (Hylobatidae or gibbons) may now be attributed too lightly to an amazing diploid chromosome number of 2n = 64. For clarity I simply discard any existing intention to derive great ape chromosomes from a similar hypothetic ancestor, confident that in the same effort nobody would try seriously to derive monkeys from great apes. All gibbons share the same three chromosomal fission events with other apes that compare with macaque chromosome numbers 2, 7 and 13 and the corresponding fissioned pairs: for humans chromosomes 7 and 21, 14 and 15, 20 and 22 respectively. This detail strongly pleads for an ultimate derivation of gibbon chromosomes from the same macaque-like ancestor having a reduced set of chromosomes (2n = 42), as well as from the same ancestral ape having 2n = 48 chromosomes like great apes. Then subsequent changes should have reduced the count for Hoolock genus to 2n = 38, an even lower diploid chromosome number than macaques, while for other gibbon genera the number is higher: 44 (Hylobates), 50 (Symphalangus) and 52 (Nomascus), respectively. This implies that all additional ape-related fusion events on chromosomal level, as observed for humans and gibbons, were preceded by these three fission events that are shared by all apes.
Fission is one way to trigger accelerated recombination, and to increase plasticity. Hybrid-driven recombination is another, whether or not in combination with the mechanism of fission. Reversely, biological justification of chromosome fusion may rather be found among the advantages of synteny, ie. the physical co-localization of genetic loci on the same chromosome. It is suggested that genetic change by hybridization is not an overnight process, and may create instability on chromosome level for at least a few generations. Hybridization of chromosomes and homogenization processes, per definition occurring after considerable divergence, opens up a whole new array of possible combinations, but also new risks of meiotic nondisposition. Natural selection could become a cumbersome, even impossible strain to reproduction if also the whole array of possible deleterious combinations would eventually result in low-fitness birth. Reproductive consequence would be less for miscarriages, or just lower rates of viable gametes. Still, even the fecundity of plants would be harmed by the possibility of unlimited recombination, not in the least for the reproductory investments of cycads that also have the record for the world’s largest sperm. Encapsulation of heterozygous content in fused chromosomes could reduce this risk to future generations. It goes without saying that fusion of chromosomes also offers a better protection against cytogenetic instability of hybrids. As such, fusion of chromosomes emerges as a potential strategy towards endogenous purifying selection and increased fitness of the hybrid lineage.
An example of chromosomal instability is trisomy, that typically results in miscarriage, or low-fitness offspring. Human low-fitness births related to trisomy are the Patau syndrome (trisomy 13), that affects somewhere between 1 in 10,000 and 1 in 21,700 live births, the Edwards syndrome (trisomy 18) that occurs in approximately 1 in 3,000 conceptions and half this rate for live births, with a median lifespan of 5–15 days, and the Down syndrome, whose incidence is due to trisomy 21 for 95% of the cases, and estimated at one per 800 – 1000 births.

Trisomies of all chromosomes with the exception of chromosome 1 have been reported in spontaneous abortions in humans; however, the only numerical autosomal anomalies surviving to birth are trisomies 13, 18, and 21. There are only six reported cases of autosomal trisomies in live horses ([…] 23, 26, 27, 28, 30, and 31) […]. Similar to that observed in humans, trisomies in horses predominantly involve small chromosomes. (Brito et al., 2008)

Human trisomy indeed involves chromosomes that are either small (18, 21), or with low gene density (13), apparently important preconditions against a spontaneous abortion. Despite the deleterious nature of the three trisomy-ridden human chromosomes mentioned above, these already existed before the lesser apes split off from great ape ancestors. Chromosomes 13 and 18 must have been present even in the common ancestor of apes and macaques. Only different gibbon genera managed to neutralize these potential dangers by fusion: in Hylobates the equivalents of human chromosomes 13, 18 and 21 are all fused (respectively with chromosomes equivalent to 3, fissioned remnants of 1 and 15).

Even though Hominoidea chromosomes 13, 14, 15, 18, 20, 21, and 22 constitute a single, uninterrupted chromosomal block in the lar gibbon, most of them are part of larger chromosomes and/or show internal rearrangements. (Misceo et al., 2008)

Such evidence may indicate that chromosome fusion is neither coincidental nor imperative per definition. This is especially interesting for the unique fusion of two ancestral great ape chromosomes into human chromosome 2.

The human chromosome number 2 is a fusion of two great ape chromosomes. Displayed are respectively the versions of humans, chimps, gorillas and orangutan. The banding pattern of chimps equals the human version most.

This fusion was evidenced by similarities in chromosome banding patterns as well as homologies in DNA sequences, where chimps make the best match. Normally, the extreme ends of chromosomes (telomeres) form a dynamic buffer against loss of internal sequences and prevent chromosomes from fusing, but apparently here telomeric DNA was involved in the fusion, to the extend that some telomeric DNA was preserved at location 2q13 near the new centromere.

Comparative cytogenetic studies in mammalian species indicate that Robertsonian changes have played a major role in karyotype evolution [..]. This study demonstrates that telomere-telomere fusion, rather than translocation after chromosome breakage, is responsible for the evolution of human chromosome 2 from ancestral ape chromosomes. (IJdo et al., 1991)

Somehow this event set us apart from great apes. As the assigned number indicates, chromosome 2 is our second largest chromosome. Commonly described as important for cognitive capacities, this particular fusion implies the importance of synteny for imposing genetic stability on cytogenetic level, that exceeds protection against semi-viable trisomy.
Evolving species may be expected to rely on an evolutionary boost to give them an edge. Since non-deleterious point mutations are rare, much depends on a quick and adequate mechanism to experiment with new complex DNA combinations. Species having low effective population sizes may have a problem if biological divergence is insufficient for regular recombination to produce successful genetic results. At major adaptive radiation events a species could recur to fission as a strategy to compensate for an initially low biological divergence. Next, increased divergence by the process of adaptive radiation may be expected to eventually reduce the need for fission – unless effective population sizes remain too low for harboring major biological variety. Lesser apes may have continued on the strategy of fission where great apes didn’t, implying their divergence probably occurred right here. Instead the lineage of great apes, including hominines, could take advantage of hybridization to incorporate successful mutations in the genome, no matter where these originated. This mechanism must have been a possibility within a certain time window, somewhere between population divergence and irreversible speciation. An extended continuation of this process may have relied on sub-species cross-breeding and hybridization – ie. contrasting with recurrent vicariance events as cited in the case of the gibbon genera, where low effective population sizes urged for continuous cytogenetic change in order to cope with the needs of environmental adaptation. Either way such periods of adaptive radiation should have left traces in the human chromosomes, not in the least if true hybridization was involved:

Contrary to the view that hybrids are lineages devoid of evolutionary value, a number of case studies are given that show how hybrids are responsible for reticulate evolution that may lead to the origin of new species. Hybrid evolution is mediated by extensive genome repatterning followed by rapid stabilization and fixation of highly adapted genotypes. Some well-documented cases demonstrate that bursts of transposition follow hybridization and may contribute to the genetic instability observed after hybridization. The mechanism that triggers transposition in hybrids is largely unknown. (Fontdevila, 2005)

Geneflow within the genetic continuum of a species happens all along, but let’s ‘[…] define hybridization as gene flow between two populations after an isolation barrier has formed between them.’ (Patterson et al., 2006 Supp.). The latter is most likely a major element in evolution, still waiting for recognition. And a potential cul de sac since, contrary to equids, zamia and gibbons, chromosomal changes in great apes and humans are far from impressive. No chromosomal fission event postdated the divergence from lesser apes, not even in hominin-specific evolution. Genetic recombination was significant enough for rapid change and plasticity, but apparently without the need for massive reorganization on chromosomal level, or even significant mutational activity on genetic level. Segmental duplications make a remarkable exception:

Although [the genomes of] terminal hominid lineages show an excess of [segmental] duplications, the most significant burst of activity (4–10-fold […]) occurs in the common ancestor of human/chimpanzee and gorilla and after divergence of gorilla from the human–chimpanzee lineage […] We note that this burst of duplication activity corresponds to a time when other mutational processes, such as point substitutions and retrotransposon activity, were slowing along the hominoid lineage. (Marques-Bonet et al., 2009)

Duplication indeed contributes to diversity, though indicative of actual genetic activity rather than anything else:

Gene models associated with signal transduction, neuronal activities (for example, neurotransmitter release, synaptic transmission) and muscle contraction are significantly enriched in human, chimpanzee and orang-utan lineage-specific duplications […]. Human and great-ape shared duplications or those shared with macaque are, in contrast, enriched for biological processes associated with amino acid metabolism […] or oncogenesis (Marques-Bonet et al., 2009)

Some sort of genomic destabilization is implied ‘at a period before and perhaps during hominid speciation’. But why and how this process could have been so different for humans, compared with an evolutionary strategy towards increased chromosomal change for lesser apes?
Exchange of alelles between hominine subspecies is nowadays sufficiently attested in modern genome research, but cross-breeding of diverging subspecies – or species! – should suggest chromosomal change of a higher order. Indeed, at least something has happened on chromosome level since the human divergence from apes, most notably the reduction of the chromosome count from 48 to 46, or the unique X-transposed region of the human Y-chromosome, dated right after chimp divergence and a virtually unprecedented event all by itself.

A third sequence class in the human MSY euchromatin — the X-transposed sequences — has no counterpart in the chimpanzee MSY. The presence of these sequences in the human MSY is the result of an X-to-Y transposition that occurred in the human lineage after its divergence from the chimpanzee lineage (Hughes et al., 2011)

Also chromosomal changes in chromosome 7, one of the new ape chromosomes that originated by fission, could be mentioned: the chromosome was subject to a pericentric inversion (including the centromere) after the divergence of orangutan, followed by a paracentric inversion after the divergence of gorilla. Another translocation of genetic information from chromosome 15 to chromosome 4 has been documented only for African apes: gorilla suffered deletions that preclude proper interpretation, but all derived basepairs of the 4q copy in chimps indicate this to be the result of hybrid recombination that happened before the divergence of gorilla:

If the duplication was followed by speciation and independent accrual of mutations, we would expect to find the human 15q and chimpanzee 15q copies to show higher identity to each other than either does to the copy found on chimpanzee 4q. Instead, the two chimpanzee copies are the most closely related pair of this trio.
By comparing ~19.1 kb of hand-curated, well-aligned block-5 sequences, we find that the chimpanzee 4q and 15q copies are only 1.43% diverged (Jukes-Cantor adjusted). They also share 43 derived mutations, including a 4-bp deletion that disrupts the ORF of gene H, not seen in the macaque or human 15q copies.
In contrast, the human 15q and chimpanzee 15q copies are 1.65% diverged and share 22 derived mutations not seen in chimpanzee 4q; and the human 15q and chimpanzee 4q copies are 1.64% diverged and share 13 derived mutations not seen in chimpanzee 15q.
(Rudd et al., 2008)

Such macro genetic events may be of an entirely different category than the published evidence that involve autosomal admixture of genetic regions from different hominine subspecies (Neanderthal, Denisova), or even of genetic harmonizing on the X-chromosome, already quoted as valid evidence for true cross-species genetic exchange with chimpanzee ancestors. Still, they are only in modest agreement with the prospected results of radical hybridization.
Notwithstanding an extended period of great ape evolution, lasting millions of years since the divergence of lesser apes, it has all appearance that over time hybridization remained a gradual process and rarely exceeded the level of subspecies crossbreeding.
Ever since this last major hybridization event(s) between chimp and human ancestors the hominine lineage apparently entered an extended period of rapid development. A full discussion is not the context of this article, but we can be sure nature did its utmost to exploit all available intra-species diversity to experiment with genetic recombination. There is an increasing awareness of natural interbreeding and admixture on subspecies level, whose impact on human evolution genetic science only started to disentangle. Another challenge still awaits us in the preposition that hominines could be essentially more related to orangutan than chimpanzees. Genetically this doesn’t seem right, but a successful hybrid is also a collation of DNA and morphology that rather define a new composition than an average of parental features. Current evidence corroborates to the implication that the genetic result of hybridization isn’t even random:

[…] endogenous selection is acting against intermediate hybrid individuals, that is, those that contain the highest number of alien genetic elements (Arnold, 1997). In a similar way, Rieseberg et al. (1996), working with H. anomalus, found that similar linkage groups of genes exist in several artificial hybrid lines with high fertility. (Fontdevila et al., 2005)

All we could propose is a complicated pattern of cross-breeding events to close the evolutionary gap of up to 16 million years since common Griphopiths precursors of great apes started to diverge.

Griphopithecins are the first cosmopolitan hominoid taxon, probably as a result of their powerful jaws and teeth that allowed them to exploit a wide variety of resources.
I see the entire region from Germany and Turkey in the north to Kenya in the south as a potential core area in which early hominids could have evolved. But there are major gaps in the record. For example, one species of Kenyapithecus is known from 16–16.5 Ma in Turkey and another from Kenya at about 13.5 Ma […]. It was probably present elsewhere in the intervening interval of time but we have not yet found the fossils. From this core area these stem hominids (not specifically related to either living group of hominids, pongines, or hominines) eventually split, with one segment of the distribution of species dispersing to the north and east and another to the north and west. The causes of this dispersal are unknown, but griphopithecins are the most primitive hominids we know. The later-occurring sivapithecins of Asia and dryopithecins of Europe are more modern, and strong cases can be made that they are related to living orangutans and African apes and humans, respectively. (Begun, 2010)

If both components indeed represent sister lineages of apes rooted in the Miocene, it would be taunting to bolster this almost impossible preposition with genetic evidence.
I suggest the fuss about our purported lack of relatedness with the apparently quite basal gibbon genera might give us an important clue. If both great ape genera acquired their humanizing features by an extended period of hybridization, their common ancestor may indeed remind us to primitive small apes:

[…] Griphopithecus and its relatives retain primitive postcrania. They are more monkey-like than ape-like […] without any indications of the suspensory capabilities of all later fossil and living great apes (Begun, 2010)

Cytogenetic evidence cited above reveals that chromosomes of small apes share the basic pattern that set great apes apart from macaques and thus may derive from an ancestor having eg. orangutan-like chromosomes. From this point onwards small apes can be defined as monophyletic, what may be confirmed by genetic evidence:

Among hominoid primates, gibbons alone contained Alu elements in their EIF1AY gene of the Y chromosome. (Kyung-Won Hong et al., 2007)

There have been different interpretations of the hylobatid evolutionary history regarding the four different gibbon genera, but: ‘Maximum likelihood and Bayesian analyses support Hoolock as the most basal, and both molecular and karyological studies have supported this alternative’ (Israfil et al., 2010).

Of all gibbon genera the genetic distances of Hoolocks (Bunopithecus), the most basal group, are closest to the human and chimp outgroups.

Much of the uncertainty was caused by the implied ‘radiation of the main genera over an interval of less than 1 Ma’, what according to Israfil’s calculations happened between 6.4-8 mya. However, if this radiation event happened completely isolated from other apes then humans and two species of chimps should have an equal genetic distance to all gibbon genera. All the contrary, when distances between taxa were estimated by two measures of sequence divergence, using DNA sequence of the complete mitochondrial control region and adjacent phenylalanine-tRNA, the Hoolock stood out as the gibbon species being closest to all outgroups – especially humans. One way to interpret this results is to consider a much closer relationship between gibbons and great apes than vanity allows us to do, and a radiation event that was less monophylitic than commonly assumed. Instead, genetic evidence would indicate the various gibbon originated by a two-stage isolation from a common source of Miocene apes that were still interconnected by geneflow. The slightly greater distances with chimps in comparison with humans would then be explicable by proceeding geneflow within the clade of great apes, and – notwithstanding an extensive and quite recent history of chimp-human hybridization – a higher degree of (spatial?) isolation for the genetic component of chimps in comparison with humans. Humanizing processes didn’t advance within the gibbon genera as much as within great apes, including orangutan, what should remind us to the primitive stage of development the griphopith ancestors of great apes really had:

[Griphopiths] are more monkey-like than ape-like, as is Proconsul, in having fore and hind limbs of roughly equal length, without any indications of the suspensory capabilities of all later fossil and living great apes (Begun, 2010)

The divergence of the lineage leading to small apes must have happened long before at least two parallel lineages of great apes ‘humanized’ together with hominines. In the fossil record brachiating of great apes seems to develop first within the Dryopith clade, and at this stage one might wonder what could be the involvement here of a gibbon-type introgression event. Contrary to our Griphopith ancestors, modern humans and great apes retain many physical characteristics that suggest a brachiator ancestor, including flexible shoulder joints and fingers well-suited for grasping.

Dryopithecus […] is known from postcranial remains, which are dramatically different from those of the griphopithecins and Proconsul. They show unambiguous indications of the importance of highly mobile limbs and suspensory positional behavior
I interpret this change to be extremely important in the evolution of the African and human clade. It allowed Dryopithecus to remain relatively large and yet retain the capacity to exploit terminal branch resources, by spreading its weight among the branches and by hanging below them to conserve energy […]. It also represents the evolutionary origins of human mobile and highly dexterous upper limbs.
In addition to being relatively primitive compared to later species, the teeth of Dryopithecus differ from those of the griphopithecins in having a thin layer of enamel and less rounded cusps. They more closely resemble the teeth of chimpanzees and have been interpreted as adaptations to a soft fruit diet, as in modern chimpanzees […]. The later occurring dryopithecins Hispanopithecus, Rudapithecus, and Ouranopithecus share even more postcranial derived characters with living great apes (Begun, 2010)

However, again the molecular dates remain difficult to reconcile with the fossil record:

The appearance of Dryopithecus at about 12 Ma parallels the first appearance of Sivapithecus at nearly the same time, suggesting that they diverged from a common ancestor possibly 13 to 16 Ma. (Begun, 2010)

The great ape-gibbon split simply doesn’t concur with the gibbon radiation dates:

Based on a consensus estimate of 15 Ma for the great ape-gibbon split, Chatterjee (2006) undertook molecular clock analyses using cytochrome b gene data and suggests the gibbon radiation dates to approximately 10.5 Ma. (Chatterjee, 2009)

This is still considerably less than the Raaum et al. (2005) estimate of a ‘divergence date of 15.0–18.5 Ma based on the entire mitochondrial genome’ (Chatterjee, 2009), thus apparently contradicting the possible hybridization signal mentioned above.
Molecular clock analysis is often used to estimate the date of speciation events in evolutionary history, but what can be said about its reliability? It didn’t come as a big surprise that paleoanthropologists were reluctant to abandon all the views they still cherished immediately for the sake of biochemistry:

[Wolpoff] admits […] that ramapithecines are also a stem group for the African apes, whose tooth enamel is very thin. This would be a full reverse evolution towards a dentition very similar to that of Dryopythecus. Is this a parsimonious hypothesis? (Bonis, review on Wolpoff, 1982)

Schwartz criticized newly adapted scenarios ‘defending presumed phylogenetic hypotheses rather than rigorous presentations of such hypotheses’, that essentially left the purported ‘reversal’ in dental characteristics of chimps and gorilla back to the primitive conditions of Dryopithecines, unanswered.

I am not swayed by blanket statements of how similar Pan and [hominines] are because most of the similarities appear to be primitive retentions, and I am so far unpersuaded by karyological and biochemical studies for similar reasons as well as others.(Schwartz, review on Wolpoff, 1982)

Even Wolpoff, trying very hard to conciliate paleoanthropology with molecular evidence, couldn’t help to incite Sarich by stating:

Probably the best way to summarize the very disparate points raised is that the “clock” simply should not work […] Consequently, although biochemical evidence seems to support a late Homo-Pan divergence, I believe this is a red herring, and that the molecular “clock”does not support any divergence time (Wolpoff, 1982)

One main issue that remains to be answered is how selective processes may have biased the genetic distances between species, and their biochemistry that, as a matter of fact, directly reflects evolutionary changes of their DNA.
Indeed, the molecular “clock” turned out unreliable because of variation ’caused, in part, by uncertainty or assumptions in key parameters, such as divergence times between species, generation times and ancestral population sizes’ (Conrad et al., 2011). But new results on the very mutation rates themselves indicate that apparently there is more internal logic to mutations on chromosome level than mathematicians were able to assume or deal with. Mutation rate differences exist and already turned out to be essentially individual:

[…] future studies promise to revolutionize our understanding of mutation processes and how they vary between individuals and between families as a result of age, genetic background and environmental exposures (Conrad et al., 2011).

This insight came too late for the immediate resurrection of our theorized ‘dental-hominoid’ ancestor, though in some act of posthumous generosity variable mutation processes should certainly provide for more nuance. How some basal species – humans, chimps and … hoolocks? – could remain genetically more ‘related’ on a molecular level than warranted by their morphological distance? Molecular constraints dictated that African apes and the hominine lineage should share a recent common ancestor, but the underpinning assumptions are still full of inconsistencies. ‘Single recent origin’ may be an interesting null-hypothesis to geneticists, but to paleoanthropology this increasingly reverts into the same unmanageable preposition as before. Molecular evidence is still a pretext to challenge common sense where it may oblige human minds to search for answers about themselves within a limited time window, that in turn implies a limited scope of geography. Adding here the constraints of emotional inquisition and lurking nationalism inherent to any limited region of choice, we could conclude ironically that paleoanthropology still finds itself right in the middle of all the fuss where Darwin’s theory of evolution once started.


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