UPDATE (2015-10-21): This post has gotten some attention from social media recently, because Ötzi has been in the news. Later analyses have made clear that our initial estimates of Neandertal ancestry in the Ötzi genome are overestimates. The source of the overestimation was sequencing and alignment errors in the ancient genomes.

It is now evident that East Asian populations have slightly more Neandertal ancestry than populations in Europe today. There is at least one ancient genome, the Oase 2 individual from the earliest Upper Paleolithic of Europe, that has substantially more Neandertal ancestry than any living European. Its Neandertal similarity is somewhat more than our original analysis suggested for Ötzi. But later Europeans, including early farmers like Ötzi, have very little ancestry from the initial Upper Paleolithic European population. There has been enormous genetic turnover within Europe, in other words. Just as we suggested in this post originally, today’s Europeans owe very little of their Neandertal heritage to early modern humans in Europe. But what seems new is that the Neolithic and other early farming peoples likewise had very little ancestry from the first modern Europeans.

More and more ancient genomes have become available for analysis in the last few years, and these have given rise to a much more complicated picture of ancient mixture than any of us anticipated only three years ago. The true fraction of Neandertal ancestry in the Ötzi genome is elevated slightly compared to the average European but still within the range of living people, and somewhat closer to the average East Asian today.

It’s my policy to leave original posts without editing and to make all updates to them clearly marked.

ORIGINAL POST:

I’ve been mobbed with e-mails from readers asking about my reaction to the new paper by Anders Eriksson and Andrea Manica in PNAS, titled “Effect of ancient population structure on the degree of polymorphism shared between modern human populations and ancient hominins” Eriksson:Manica:2012 . The paper asserts that Neandertal similarity in the genomes of living people outside Africa can be explained only in terms of incomplete lineage sorting from the shared human-Neandertal common ancestral population in Africa. If the paper’s assertions were accurate, we could go back to thinking that all the genetic heritage of people today traces back to Africa, although we would still need to abandon the idea that the African population had undergone a small bottleneck.

I have not been posting as frequently the last month or two because I have been out of the country doing science.

The new paper’s press release has given rise to quite a lot of media attention, much of which unfortunately misrepresents our current knowledge of human and Neandertal genomes. Razib Khan summarized the situation on Monday, in a post titled, “Why you shouldn’t publish in PNAS”. I agree with his criticism, although I have a perspective coming out soon in PNAS. In fact, I suppose this episode shows why everyone should publish in PNAS, because so many journalists will just parrot press releases instead of asking relevant experts. Ewen Callaway did a great job on this story by putting it into the broader context (“Neandertal sex debate highlights benefits of pre-publication”). You will notice how no other science writers with any Neandertal knowledge picked up this press release…

Paleoanthropology is a field where data are rare and precious, and we do a lot of arguing about the validity of models. I love arguing about the validity of models (Cliff Notes version: All models are wrong).

Genomics is not such a field. We have abundant data today to compare with Neandertal genomes. Yet puzzlingly, the idea of Neandertal ancestry has been challenged by several papers that haven’t performed any new empirical comparisons at all. I’m struggling to figure this out. We have an unparalleled ability to explore the genomes of humans and Neandertals, and we should believe a computer model with no empirical data?

I’ve been assessing the Neandertal similarity of 1000 Genomes Project samples here on my blog (e.g., “Which population in the 1000 Genomes Project samples has the most Neandertal similarity?”). This is ongoing research here in my group, but we’ve been making it open because it tells us immediately that some hypotheses about Neandertal similarity must be wrong. Modeling is a lot of work. We’re trying to avoid putting a lot of investment into modeling that will be easily refuted by the next piece of genomic data. Data are flowing now so rapidly that we can afford to be naive empiricists.

For example, our comparisons quickly refute the hypothesis that Neandertal similarity comes only from ancient population structure in Africa. That hypothesis predicts much more heterogeneity within Africans in Neandertal similarity than exists today. We’ve shown that the heterogeneity in Africans is basically the same as within Europeans or Asians, and that the variance among African populations so far is quite small. Those are very simple observations, which are consistent with what Yang and colleagues Yang:ancient:2012 concluded on the basis of the frequency spectrum of Neandertal alleles in large samples of living people. Even though many Neandertal-shared SNP alleles came from incomplete lineage sorting, the signature of excess Neandertal sharing outside Africa must come mostly from recent introgression. In Ewen Callaway’s article about this research, David Reich dismissed the new paper by Eriksson and Manica as “obsolete”</a>. I agree. The paper describes a model without carrying out any new empirical comparisons, and so has fallen behind where the science has gone.

Another example is the proportion of Neandertal ancestry. Initially, the proportion of ancestry from Neandertals in living people was argued to be between 1 and 4 percent Green:draft:2010 . That was a model-based estimate that was the best possible under the assumption that Africans have no Neandertal ancestry. We now have a lot more human comparisons, which would make possible a more precise estimate of the mean. I hesitate to provide a new estimate, because we have shown that some Africans have substantial evidence of Neandertal similarity, which throws the baseline for any estimate into question. How much Neandertal ancestry is present in living people must depend on a more complex model of mixture among later populations. The result will still be small (probably less than 6 percent) but understanding this proportion will help us to evaluate when and where Neandertal genes flowed into our populations.

Here’s a third example. I haven’t written about here yet, but I have been lecturing about it quite widely over the past few months. Earlier this year, the genome of Ötzi the Tyrolean Iceman was reported by Andreas Keller and colleagues Keller:iceman:2012 . Aaron Sams and I downloaded the data and have been carrying out several different kinds of comparisons. A picture:

I’d like to see the model of African population structure that could explain this result…

If you’ll remember my earlier posts on the 1000 Genomes Project samples, this chart is a histogram of the number of shared Neandertal derived SNP alleles in different samples. The European and Asian samples are substantially greater than either African sample (here, Luhya and Yoruba colored differently). If we took as a baseline that Europeans have an average of 3.5 percent Neandertal, Ötzi would have around 5.5 percent (again, the actual percentage would be highly model-dependent). He has substantially greater sharing with Neandertals than any other recent person we have ever examined.

You can imagine, we have carried out just about every comparison we can think that could explain this result as anything other than greater Neandertal ancestry. Aaron and I will be putting our manuscript on the arXiv as soon as we’ve both signed off on all the text and figures, hopefully this week. This is simple stuff, and I see no reason not to be open about it – anybody with the Ötzi data can immediately do the same thing.

We think that showing and sharing these comparisons will save people a lot of useless effort. Personally, I can’t believe that these people spending effort on population models for Neandertals aren’t talking to those of us who have already carried out these comparisons and have already presented them in public. I guess we’ll find out if secrecy or openness leads to better science.

Meanwhile, I can share the abstract of the conference paper I’ll be presenting in September at the meeting of the European Society of Human Evolution in Bordeaux:

Evaluating recent evolution, migration and Neandertal ancestry in the Tyrolean Iceman

Paleogenetic evidence from Neandertals, the Neolithic and other eras has the potential to transform our knowledge of human population dynamics. Previous work has established the level of contribution of Neandertals to living human populations. Here, I consider data from the Tyrolean Iceman. The genome of this Neolithic-era individual shows a substantially higher degree of Neandertal ancestry than living Europeans. This comparison suggests that early Upper Paleolithic Europeans may have mixed with Neandertals to a greater degree than other modern human populations. I also use this genome to evaluate the pattern of selection in post-Neolithic Europeans. In large part, the evidence of selection from living peoples genetic data is confirmed by this specimen, but in some cases selection may be disproved by the Icemans genotypes. Neolithic-living human comparisons provide information about migration and diffusion of genes into Europe. I compare these data to the situation within Neandertals, and the transition of Neandertals to Upper Paleolithic populations three demographic transitions in Europe that generated strong genetic disequilibria in successive populations.