Tag: Neanderthals

What Neanderthals tells us about modern humans

Posted on by Razib Khan

In Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past David Reich spends a fair amount of time on Neanderthal admixture into modern human lineages. Reich details exactly the process of how his team arrived to analyze the data that Svante Paabo’s group had produced, and how they replicated some peculiar patterns. In short, eventually, they concluded that modern humans outside of Africa have Neanderthal ancestry, because the Neanderthal genome that Paabo’s group had recovered happened to be subtly, but distinctively, closer to all non-Africans than to Africans. At the time, the group reported that Neanderthal ancestry was relatively evenly spread across non-African populations, which lead them to suggest that it was likely a singular admixture event early on during the expansion phase of modern humans.

Nearly a decade things have changed. There is a consistent pattern of West Eurasians having less Neanderthal ancestry than East Eurasians. That is, Europeans have lower Neanderthal ancestry fractions than Chinese (South Asians are in between, in direct proportion to their West Eurasian ancestral quantum). There have been a variety of arguments and explanations for why this might be, which fall into two classes:

  1. Neanderthal ancestry was purged more efficiently from West Eurasians due to larger effective population sizes (selection is stronger in large populations).
  2. There may have been multiple admixture events into modern humans, or, gene-flow into West Eurasians diluting their Neanderthal ancestry.

But what if all these arguments are mostly wrong? That’s what a new preprint seems to suggest: The limits of long-term selection against Neandertal introgression:

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans due to deleterious alleles that had accumulated in the Neandertals after they split from the modern human lineage. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45 thousand years. Here we show that this apparent decline is an artifact caused by gene flow between West Eurasians and Africans, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When applying a more robust statistic that takes advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Western Europe over the past 45 thousand years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters, and find that negative selection is not expected to cause a significant long- term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular a depletion of Neandertal ancestry in conserved genomic regions that are likely to be of functional importance. Thus, we find that negative selection against Neandertal ancestry has not played as strong a role in recent human evolution as had previously been assumed.

The basic argument in the preprint is that the model assumed for the ancestry of West Eurasians and Africans was wrong. Wrong assumptions can lead to wrong inferences. Using two Neanderthal genomes which are from different populations, one of whom directly contributed to the Neanderthal ancestry in modern humans, a new statistic which was insensitive to model assumptions about modern human phylogeny was computed.

The older statistic held that West Eurasians and Africans were distinct clades which had not had gene flow in ~50,000 years. Using simulations the authors argue that the best fit to the statistics that they do see, the earlier flawed one, and the current more robust one, is a situation where a population of West Eurasian origin mixed with Africans starting about ~20,000 years ago.

This explains why there was a consistent decline in Neanderthal ancestry: the earlier statistic’s model assumption got worse and worse over time, and so began to underestimate Neanderthal ancestry more and more. There was continuous gene flow into Africa over the past 20,000 years.

Not everything that came before is wrong. It could still be that there are multiple admixtures. And, the authors do agree that some selection for Neanderthal alleles has occurred. It’s just that it’s not the primary reason for the decline of Neanderthal ancestry in West Eurasians.

As for the other explanation, that Neanderthal-less Basal Eurasian ancestry diluted the European hunter-gatherer fractions, the authors seem very skeptical of that. One point the authors make is that though an early European farmer was estimated to have ~40% Basal Eurasian, its Neanderthal estimate is still quite high. Iosif Lazaridis points out that this is an old estimate, and the Reich group now puts it closer to ~25%. Additionally, another recent preprint put the fraction closer to ~10%. With such low values, it is possible that Basal Eurasians may have had low Neanderthal fractions, but that that was a marginal effect on the aggregate West Eurasian ancestry quantum from Neanderthals.

I think the bigger thing to consider is that our understanding of the relationships of modern humans is roughly right, but there are lots of nuanced details we’re missing or misunderstanding. Ancient DNA from South Africa, for example, shows that modern Bushmen all seem to have exotic ancestry compared to samples from 2,000 years ago. But what about samples from 20,000 years ago?

We have the best temporal transect from Ice Age Europe, and in this region, there are many population turnovers and admixtures. It seems implausible that Europe is entirely exceptional. The West Eurasian gene flow event dated to ~20,000 years ago is curiously coincidental with the beginning of the recession of the Last Glacial Maximum. To get a better understanding of the relationships of Pleistocene people looking at paleoclimate data is probably useful. The ancient DNA will come online at some point…and unless you think ahead, we’re going to be surprised.

The Loneliest Neanderthal

Posted on by Razib Khan

Neanderthals are in the news again! This is good for me personally, as my company is selling Neanderthal trait analysis. Ooga-booga!

In any case, the two papers which have triggered the current wave of Neandermania are The Contribution of Neanderthals to Phenotypic Variation in Modern Humans, and A high-coverage Neandertal genome from Vindija Cave in Croatia. They are somewhat different. The first publication looks at introgressed archaic variants within modern populations. The second gets some results out of a much higher quality European Neanderthal which lived ~50,000 years ago.

The cool thing about the first paper is that it combined UK Biobank data, 100,000+ individuals, with hundreds of thousands of markers, and Neanderthal genomic data. Note that: a paper comparing ancient genomes with over 100,000 individuals and hundreds of thousands of markers. Now that’s 2017!

To find archaic alleles they:

  1. Looked for variants fixed in Yoruba (no Neanderthal), and homozygote or heterozygote in the alternative state in the Altai Neanderthal, which also segregated (varied) in the UK Biobank population. Basically, an allele not found in Africans but found in Neanderthals, and also found in appreciable fractions in the UK Biobank data set.
  2. They then took the SNPs above, and only retained ones confidently embedded in tracts of Neanderthal ancestry. Haplotype was consistent with admixture ~50,000 years ago (the length), and exhibited lower distance to Neanderthal than African genomes.

They did some stuff with tag-SNPs though. Overall they found a lot of the usual suspects. Pigmentation. Chronotype. But this passage jumped out at me:

In fact, for most associations, Neanderthal variants do not seem to contribute more than non-archaic variants. However, there are four phenotypes, all behavioral, to which Neanderthal alleles contribute more phenotypic variation than non-archaic alleles: chronotype, loneliness or isolation, frequency of unenthusiasm or disinterest in the last 2 weeks, and smoking status.

What they are saying is that for a lot of traits Neanderthals don’t really change the direction of the trait in humans, they just add more variants. This seems to be the case in pigmentation. Entirely unsurprising, Neanderthals were around for hundreds of thousands of years. Of course they had a lot of variation amongst themselves.

But the behavioral traits above shifted the modern humans in the aggregate who had the archaic allele somewhat. That is, being Neanderthal derived made a difference.

There have long been speculations about the sociality (or lack thereof) of Neanderthals. It would not be surprising if small population sizes meant that Neanderthals were less gregarious than modern humans, and that their lack of gregariousness did not redound to their benefit when they encountered the last wave of moderns.

Which brings us to the second paper. The big deal here is that it gives us a very high quality ancient genome of a European Neanderthal that lived ~50,000 years ago (the Vindija sample). Before this we had a high quality ancient genome of an Asian Neanderthal that lived ~125,000 years ago (Altai sample).  ~75,000 years is a long time. It’s so long that almost all the ancestry of modern non-Africans would have converged to a common population that long ago. Additionally, all the available data indicate that most of the admixture into modern humans from Neanderthals occurred around 50,000 years ago. So this new sample is definitely welcome.

It is not surprising that the Vindijia sample seems to be closer to the Neanderthal admixture population than the Altai sample. First, it is likely geographically closer, since all non-African populations have some Neanderthal ancestry West Asia is probably the top candidate, and southeastern Europe is not that far from West Asia in comparison to Mongolia. Second, it is basically contemporaneous with the Neanderthals who contributed ancestry to modern humans who left Africa. This means that the Neanderthal admixture percentage in non-Africans goes up moderately.

To me this is the most important paragraph:

It has been suggested that Denisovans received gene flow from a human lineage that diverged prior to the common ancestor of modern humans, Neandertals and Denisovans (2). In addition, it has been suggested that the ancestors of the Altai Neandertal received gene flow from early modern humans that may not have affected the ancestors of European Neandertals (13). In agreement with these studies, we find that the Denisovan genome carries fewer derived alleles that are fixed in Africans, and thus tend to be older, than the Altai Neandertal genome while the Altai genome carries more derived alleles that are of lower frequency in Africa, and thus younger, than the Denisovan genome (20). However, the Vindija and Altai genomes do not differ significantly in the sharing of derived alleles with Africans indicating that they may not differ with respect to their putative interactions with early modern humans (Fig. 3A & B). Thus, in contrast to earlier analyses of chromosome 21 data for the European Neandertals (13), analyses of the full genomes suggest that the putative early modern human gene flow into Neandertals occurred prior to the divergence of the populations ancestral to the Vindija and Altai Neandertals ~130-145 thousand years ago (Fig. 2). Coalescent simulations show that a model with only gene flow from a deeply diverged hominin into Denisovan ancestors explains the data better than one with only gene flow from early modern humans into Neandertal ancestors, but that a model involving both gene flows explains the data even better. It is likely that gene flow occurred between many or even most hominin groups in the late Pleistocene and that more such events will be detected as more ancient genomes of high quality become available.

These results seem to support earlier work indicate that Denisovans were admixed with an ancient hominin group which diverged very early on (probably the descendents of East Asia erectus?). And, that Neanderthals received gene flow from a lineage of modern (African?) humans 150,000 or more years ago. Since the latest work suggests that modern humans in some form have existed between from 200,000 to 350,000 years ago, this is entirely plausible.

But, it brings us the take-home message that the emergence of Pleistocene humanity was to a some extent characterized by reticulate gene flow, rather than a bifurcating tree.