The date of 37,000–86,000 years BP [for Neanderthal admixture/genetic overlap with modern humans as measured by linkage disequalibrium genetic methods] is too recent to be consistent with the “ancient African population structure” scenario, and strongly supports the hypothesis that at least some of the signal of Neandertals being more closely related to non-Africans than to Africans is due to recent gene flow. These results are concordant with a recent paper by Yang et al that analyzed joint allele frequency spectra in Africans, non-Africans and Neandertals, to reject the ancient structure scenario.Note: I include almost the entire conclusion rather than select excerpts, despite copyright to capture numerous important qualifiers to the conclusion in the original and feel that this constitutes fair use particularly in light of the fact that this is an open access, basic science publication.
After the present paper was accepted, Eriksson and Manica showed, using an Approximate Bayesian Computation approach, that models of ancient substructure can produce a signal of Neandertals sharing more derived alleles with non-Africans than with Africans (that is, they can account for the observation that D-statistics are significantly different from zero). The same observation was made in our earlier papers on the draft Neandertal and Denisovan genomes where we introduced D-statistics. However, the new statistics we focus on here as well as the statistics focused on by Yang et al show that ancient structure alone cannot explain these signals.
One possibility that we have not ruled out is that both ancient structure and gene flow occurred in the history of non-Africans. In the simulations reported in Table 1, we show that in this scenario, the ancient structure will tend to make the date estimate older than the truth but by not more than 15%, so that the date of 37,000–86,000 should still provide a valid bound while the less conservative estimate of 47,000–65,000 years should be interpreted as an upper bound on the date of gene flow.
Further, we have not been able to differentiate amongst variants of the recent gene flow scenario: a single episode or multiple episodes of gene flow or continuous gene flow over an extended period of time. Our date has a clear interpretation as the time of last gene exchange under a scenario of a single instantaneous gene flow event. In the other scenarios, the date is expected to represent an average over the times of gene flow and should be interpreted as an upper bound on the time of last gene exchange.
While recent gene flow from Neandertals into the ancestors of modern non-Africans is a parsimonious model that is consistent with our results, our analysis cannot reject the possibility that gene flow did not involve Neandertals themselves, but instead populations that were more closely related to Neandertals than any extant populations are today. Thus, the date should be interpreted as the last period of time when genetic material from Neandertals or an archaic population related to Neandertals entered modern humans.
Genetic analyses by themselves offer no indication of where gene flow may have occurred geographically. However, the date in conjunction with the archaeological evidence suggests that the two populations likely met somewhere in Western Eurasia. An attractive hypothesis is the Middle East, where archaeological and fossil evidence indicate that modern humans appeared before 100,000 years ago (as reflected by the modern human remains in Skhul and Qafzeh caves), Neandertals expanded around 70,000 years ago (as reflected for example by the Neandertal remains at Tabun Cave), and modern humans re-appeared around 50,000 years ago.
Our genetic date estimates, which have a mostly likely range of 47,000–65,000 years ago (and are confidently below 86,000 years ago), are too recent to be consistent with the appearance of the first fossil evidence of modern humans outside of Africa—that is, our date makes it unlikely that the Neandertal genetic material in modern humans today could arise exclusively due to the gene flow involving the Skhul/Qafzeh modern humans—and instead point to gene flow in a more recent period, possibly when modern humans carrying Upper Paleolithic technologies expanded out of Africa.
LD methods of dating are far less controversial than mutation rate dates. They rely on some basic and well established features of the recombination process at each generation, and essentially measure how well shuffled SNPs are as a result of that process, rather than the number of mutations against some baseline found in a genome.
This study, together with other recent research, establishes that:
1. Neanderthal admixture with Eurasian modern humans (or admixture with archaic hominins more closely related to Neanderthals than to modern humans or Denisovans) did take place sometime in the Middle Stone Age or Upper Paleolithic era, rather than simply be an artifact of ancient population structure, even though there may be some contribution from ancient population structure.
It is clear from ancient DNA and other evidence that there was indeed significant population structure among both Neanderthals and modern humans in the Middle Stone Age and Upper Paleolithic. Ancient DNA shows some level of regional differentiation in Neanderthal genetics. Similarly, Eurasian uniparental mtDNA and Y-DNA phylogenies are derived from only a small subset of Africa's population genetic diversity (unsurpisingly, the subset likely to have origins in the vicinity of the geographic areas in Africa where modern humans first left that continent).
It is not at all clear that Eurasian modern humans had much internal population structure prior to a schism between West Eurasian and East Eurasian populations, although uniparental genetic phylogenies are not inconsistent with the possibility that there could have been two or three subgroups of Eurasians with significant population structure.
It is also not clear how much of the current internal genetic diversity in West Eurasians and in East Eurasians that is not clearly attributable to mutations arising in situ in the first populations present in a geographic area, was present from the start, as opposed to arising from subsequent wave of migration. A material part of the genetic diversity in modern populations, at least, is derived from later migration waves and was not present when the first modern humans arrived at particular location in Europe and Asia. Likewise, some of the genetic diversity present in the earliest Eurasian populations must have involved genetic features found only in populations that have since gone extinct.
2. Most of the admixture evidence in modern humans alive today took place before modern humans arrived in Europe, but after they left Africa.
3. At least some of the admixture took place at a time closer to an "Out of Arabia" date than to an "Out of Africa" date given the increasing archaeological evidence for an Out of Africa date before 100kya. (No one seriously argues that modern Eurasians are descendants predominantly from initial Out of Africa migrants via Spain or Italy, rather than via Israel or southern Arabia.)
4. The study does not resolve whether admixture happened before, after, or both before and after, the ancestors of modern Eurasians split into West Eurasian and East Eurasian populations.
There is relatively little overlap between the Neanderthal SNPs found in West Eurasians and the Neanderthal SNPs found in East Eurasians, suggesting that either parallel admixture events as the source of at least some admixture in these populations, or founder effects at the time of the West Eurasian-East Eurasian schism prior to Neanderthal admixture reaching a point of fixation are the most likely source of this distinction. This schism is nearly complete no further east than the India-Burma border.
5. Neither this study, nor previous ones, provide much insight into whether admixture was a punctuated event or a gradual process over millenia of co-existence. The absolute number of admixture events and the effective population size of the early Eurasians at the time of Neanderthal admixture are not very tightly constrained. We do know that there is no Neanderthal mtDNA or Y-DNA in any modern human now living (out of more than a hundred thousand people tested in a way that oversamples potentially significant outliers) or in any ancient DNA from a modern human. We do know that East Eurasian Neanderthal admixture preceded Denisovan admixture in the proto-populations that gave rise to Papuans and aboriginal Australians.
6. There is considerable reason to believe from ancient DNA evidence and circumstantial evidence that indigeneous European hunter-gatherer populations (and populations with large demographic contributions from these populations that transitioned in food production methods) had much higher levels of Neanderthal admixture than modern European or Asian populations, as a result of additional Neanderthal admixture taking place upon arrival in Europe. This persisted in parts of Europe at least until the Copper age (ca. 3500 BCE).
The most plausible explanation for why this is no longer the case is that subsequent waves of migration after Neanderthals went extinct a little less than 30,000 years ago, by people who lacked this elevated level of Neanderthal admixture into Europe because their ancestors were from places where Neanderthals ceased to be present much earlier, have diluted the admixture levels seen in modern European populations. This suggests that there were very significant demic contributions from outside Europe (or at least from the European far fringe) to European population genetics within the last 5,500 years or so.
Source: Sriram Sankararaman, Nick Patterson, Heng Li, Svante Pääbo, David Reich
"The Date of Interbreeding between Neandertals and Modern Humans," PLOS Genetics, October 2012 link.