Razib Khan One-stop-shopping for all of my content

January 21, 2012

The erectus within?

The Pith: More caveman admixture in modern humans, especially Melanesians!

A new paper on archaic adaptive introgression among Melanesians has been discussed elsewhere. But I think it is worth reviewing, because it’s probably a foretaste of what’s to come. Researchers are combing through the human genome, as more and more genomes come on line, in the search of weird and unexpected variation. The paper is in Molecular Biology and Evolution, and is titled Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations (why is it that this journal doesn’t even allow supplemental information to be free to the public?). The two primary figures from this paper do a good job of illustrating the main result.

The first figure is a phylogenetic tree of haplotypes at the OAS1 locus, with pie charts showing the proportion of individuals from a set of populations which contribute to the total number for that haplotye. So you see above that the “deep lineage” is relatively distant from a cluster of other haplotypes (as measured by mutational differences which are proportional to depth of common ancestry), and, that deep linage is exclusively found in Papuans in this set. The second figure shows the frequency of the deep lineage haplotype over a larger set of populations. I cut off the section which shows that Africans are at zero percent. The haplotype is found almost exclusively in Melanesian populations, except for the fact out of over 200 South Asians they sampled, 3 of them carried it (2 Pakistanis, 1 Sri Lankan). There is aspect though not evident in the figures above, but which is clear in the abstract that you need to know:

Recent analysis of DNA extracted from two Eurasian forms of archaic human show that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. While these genome-wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene, OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We re-sequenced a 7 kb region encompassing the OAS1gene in 88 individuals from 6 Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5′ region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 million years, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ∼90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia.

There there is “more genetic diversity within Africa” is a cliche rooted in reality. But, this is not true at all genes. For example, at MC1R Africans have less genetic diversity than Europeans. Why? MC1R is implicated in pigmentation, and this locus is subject to strong functional constraint at low latitudes. In other words, there is more at work than just demographic history. When you see more diversity at a locus outside of Africa than within there is a strong suspicion that natural selection or admixture may be at play, because your null expectation is that the dominant “Out of Africa” event will imply more Africa diversity or modern humans. So at OSA1 you have a genetic variation which is very diverse, and very divergent, from the modal human variant. When you take away the deep lineage you also see a pattern which is constant with genome wide expectations. Africans are distributed across the unrooted tree, while non-Africans seem to be nested within a subset of nodes.

But if this was published in 2008 it might not be as notable, because the human genome is big, and there are going to be random patterns here and there. This might have been dismissed. The key is that the authors matched this divergent haplotype to the variant found in the draft Denisovan genome. Naturally it’s going to be harder to dismiss as a statistical fluke when you actually have concrete evidence in this form that the ancient lineage was shared with an archaic hominin group.

There are two scientific points that jump out at me. First, the authors don’t discuss adaptation or selection in very much detail (except to dismiss balancing selection). But if this is due to archaic admixture its fraction in Melanesians is far higher than the genome wide average. Again, some loci will naturally deviate from expected values, but those that do are excellent candidates for being targets of adaptation. And, this gene has a clear functional role related to immune response. Second, the presence of this haplotype in South Asians is strongly suggestive of the location of the admixture event between archaic humans and the ancestors of modern Melanesians. This sort of information needs to be synthesized with the two papers last fall that came out on Australian evolutionary genomics.  One of the interesting aspects of the Denisovan admixture analyses is that it doesn’t seem that any South Asian group, including Andaman Islanders, exhibit it. And yet a few South Asians here carry a haplotype similar to the Denisovan variant. Interestingly, the authors present a rather unbelievable large value for the common ancestor between the deep lineage and other modern haplotypes, ~3 million years, which is an order of magnitude more than the divergence of Denisovans from modern humans.

How to resolve this confused situation? In the conclusion they point to the possibility that this haplotype may have introgressed into both the Denisovans and modern humans from H. erectus! The most recent genomics on Melanesians implies that their own history is relatively complex. On the one hand they may be some of the earliest distinct migrants out of Africa, and secondarily, they themselves may be successive compounds between those early migrants, archaic humans, and a second wave of Eurasians. All that being said, I think there is some hope in the combination of full genome sequencing of modern populations as well as the same of ancient populations via DNA from subfossils. The main qualification is that I doubt we’ll ever get good samples of ancient DNA from the tropics.

Citation: Fernando L. Mendez, Joseph C. Watkins, and Michael F. Hammer,
Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations, Mol Biol, doi:10.1093/molbev/msr301

Image credit: Wikipedia

June 16, 2011

Massive Neandertal & Denisovan introgression

Update: John Hawks’ lab is working in the same area, and he disagrees with the specific results presented here. Always reminds you to be careful about sexy results presented at conference! (someone should do a study!)

So claimed Peter Parham at a Royal Society meeting last week, Human evolution, migration and history revealed by genetics, immunity and infection. You can actually listen to the talk by pulling down the mp3 file. To get the part about human evolution and introgression, jump to 24 minutes in.

Here is the general sketch: It looks like ~50 percent of the HLA Class I alleles in Europeans derive from Neandertals, ~70-80 percent of HLA Class I alleles in East Asians derive from Denisovans, and that and ~90-95 percent of HLA Class I alleles in Papuans derive from Denisovans. If you recall, ~2.5% of the total genome content of non-Africans seems to be Neandertal, while ~5% of the total genome content of Papuans seems to be Denisovan. The total genome content proportions are rough estimates, there may be some wiggle room in there. But you can see that the HLA allele admixture estimates from these ancient Eurasian lineages is greater by an order ...

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