Abstract
The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers.
Highlights
The American continent was the last to be colonized by humans
The extant Native American populations are the result of a single migratory wave that entered the American continent at the end of the last glacial period, after a period from 5,000–8,000 years before present (YBP) in Beringia, which allowed the genetic differentiation of the First Americans [1, 4,5,6]
For the 23 Native American populations and one Siberian we identified 36 alleles at HLA-A, 80 at HLA-B, 29 at HLA-C, and 38 at DRB1, at the two-field level of resolution (S1 Table)
Summary
Most genetic studies corroborate the hypothesis that the first individuals came to America from Northeast Asia, Siberia, about 15,000 to 18,000 years before present (YBP) through the Beringia land bridge [1,2,3]. According to this hypothesis, the extant Native American populations are the result of a single migratory wave that entered the American continent at the end of the last glacial period, after a period from 5,000–8,000 YBP in Beringia, which allowed the genetic differentiation of the First Americans [1, 4,5,6]. The hypothesis of direct contribution of these groups by marine routes was proposed a while ago [13], bioanthropological studies suggest that at the end of the Pleistocene the paleoamerican populations had greater morphological diversity shared with common ancestors of South Asia and Oceania, and that these characteristics may have been retained in some populations or individuals [14, 15]
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