The Loneliest Neanderthal

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.

Population structure in Neanderthals leads to genetic homogeneity


The above tweet is in response to a article which reports on the finding past month in PNAS, Early history of Neanderthals and Denisovans. It’s open access, you should read it. I don’t think I’ve reviewed it because I haven’t dug through the supplements. To be frank this is a paper where you pretty much have to read the supplements because they’re introducing a somewhat different model here than is the norm.

I talked to Alan Rogers at SMBE about this paper. Broadly, I think there might be something to it, and it’s because of what David says above. It is simply hard to imagine that Neanderthals could be extremely successful with such low genetic diversity as we see, and spread so thin. Now, the Quanta Magazine tries to emphasize that the effective population is not the true census population, but I wish it would have explained it more clearly. Basically, the size that is relevant for breeding is obviously not going to the same as a head count. And, because effective populations are highly sensitive to bottlenecks you can get really small numbers even when the extant population at any given time may be large.

The PNAS paper makes some novel inferences, and I’ll set that to the side until I read the supplements. But I don’t think it’s crazy that population structure within Neanderthals could be leading to lower total genetic diversity.

Pegging the human expansion of out of Africa

Genetic science is good at many things, but precise dates have not always been its strong suit. There are many reasons for this, and the possibility of variable mutation rates puts a major a barrier in our ability to get absolute precision. From what I can archaeology is a little better here, despite all the problems that this discipline has.

Early human occupation of a maritime desert, Barrow Island, North-West Australia:

. In this first major synthesis we focus on the dating and sedimentology of Boodie Cave to establish the framework for ongoing analysis of cultural materials. We present new data on these cultural assemblages – including charcoal, faunal remains and lithics – integrated with micromorphology, sedimentary history and dating by four independent laboratories. First occupation occurs between 51.1 and 46.2 ka, overlapping with the earliest dates for occupation of Australia. Marine resources are incorporated into dietary assemblages by 42.5 ka and continue to be transported to the cave through all periods of occupation, despite fluctuating sea levels and dramatic extensions of the coastal plain.

The best current work sees to suggest that unlike most world populations Australians have not experienced much turnover. That is, the first settlers are the ancestors by and large of the current native populations. If this is correct we’re getting some really clear lower bound values for the date of Neanderthal and Denisovan admixture into our lineage.