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Health

Sleeping like a Neandertal

Gene ExpressionBy Razib KhanJune 25, 2012 6:36 PM

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Forgot to highlight one of the coolest abstracts from SMBE 2012, A genomewide map of Neandertal ancestry in modern humans:

2. The map allows us to identify Neandertal alleles that have been the target of selection since introgression. We identified over 100 regions in which the frequency of Neandertal ancestry is extremely unlikely under a model of neutral evolution. The highest frequency region on chromosome 4 has a frequency of Neandertal ancestry of about 85% in Europe and overlaps CLOCK, a key gene in Circadian function in mammals. The high frequency, Neandertal-derived variant is specific to Europeans; it is not very common in East Asians. This gene has been found in other selection scans in Eurasian populations, but has never before been linked to Neandertal gene flow

One of the predictions of assimilation of a large intrusive population with a small but long endemic population is that there will be biased representation of adaptive alleles from the latter into the former. In other words, if genome-wide admixture is on the order of 5% from the latter into the former, alleles which confer local fitness benefits will be present in the descendants of the asymmetric admixture in proportions of out sync with the expected frequencies. In this case the Neandertal admixture is < 5%, but the Neandertal variant may be as high as ~85%. Not only that, the authors have found an excellent and plausible candidate for Neandertal-specific adaptive alleles: we know that this H. sapiens lineage was present at high latitudes for hundreds of thousands of years! But some cautions. First, there is going to be variation around expected values of admixture of any given genomic region. There will be many segments where the descendant populations don't have any signature of Neandertal admixture, and a few segments where the Neandertal allele predominates, through random chance. Second, we need to be careful of being too eager to find what we're looking for. If, for example, you find a genomic region enriched for Neandertal ancestry one of the first things you'll no doubt do is pull up all the genes in that region, and identify plausible candidates for selection. But given a large enough genomic region, you are guaranteed to find a "plausible" candidate. This is why a "map" of the Neandertal genome is essential. To assess the probabilities you need prior expectations pegged in. Hopefully these caveats will be rendered moot in the near future as many more researchers start digging into the data. What I do find somewhat confusing is how adamant some of the original authors of the first Neandertal ancient genome paper were about the lack of evidence of adaptation.

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