Polymorphism of the HLA class II loci in Siberian populations

Abstract

The populations that colonized Siberia diverged from one another in the Paleolithic and evolved in isolation until today. These populations are therefore a rich source of information about the conditions under which the initial divergence of modern humans occurred. In the present study we used the HLA system, first, to investigate the evolution of the human major histocompatibility complex (MHC) itself, and second, to reveal the relationships among Siberian populations. We determined allelic frequencies at five HLA class II loci (DRB1, DQA1, DQB1, DPA1, and DPB1) in seven Siberian populations (Ket, Evenk, Koryak, Chukchi, Nivkh, Udege, and Siberian Eskimo) by the combination of single-stranded conformational polymorphism and DNA sequencing analysis. We then used the gene frequency data to deduce the HLA class II haplotypes and their frequencies. Despite high polymorphism at four of the five loci, no new alleles could be detected. This finding is consistent with a conserved evolution of human class II MHC genes. We found a high number of HLA class II haplotypes in Siberian populations. More haplotypes have been found in Siberia than in any other population. Some of the haplotypes are shared with non-Siberian populations, but most of them are new, and some represent "forbidden" combinations of DQA1 and DQB1 alleles. We suggest that a set of "public" haplotypes was brought to Siberia with the colonizers but that most of the new haplotypes were generated in Siberia by recombination and are part of a haplotype pool that is turning over rapidly. The allelic frequencies at the DRB1 locus divide the Siberian populations into eastern and central Siberian branches; only the former shows a clear genealogical relationship to Amerinds.

Ancestry and kinships of native Siberian populations: The HLA evidence

“…html), but of these only 16 to 25 alleles are present in any given Siberian population. [22][23][24][25][26][27] Altogether, 34 out of 329, eight out of 24, and 14 out of 53 known HLA-DRB1, -DQA1, and -DQB1 alleles, respectively, have been found in the assemblage of the Siberian ethnic groups.…”

Consequences of Population Structure on Genes Under Balancing Selection

“…In addition to the large and growing literature relating patterns of MHC polymorphism to known or inferred historical migration patterns (Arnaiz-Villena et al 1997;Erlich et al 1997;Grahovac et al 1998;Hatta et al 1999), there has recently been interest in using genes under balancing selection to study population differentiation directly. These studies assume that genes under selection can possibly tell us something about differentiation due to selective differences among subpopulations, which may be of particular interest in some species that are targets of conservation efforts, such as salmon Kim et al 1999) or bighorn sheep (Boyce et al 1997).…”

The neutral theory and natural selection in the HLA region

“…Recent survey of Siberian populations for class II haplotypes showed that more haplotypes are found in Siberian than in any other population and that most of them have been generated by recombination since the colonization of the subcontinent 40,000 years ago (24). The finding of new combinations between DQA1 and DQB1 molecules that are rarely found in other areas indicated frequent occurrences of recombination during the past 2,000 generations.…”

“…Third, the silent differences within and between class II DRB1 allelic lineages are presented to discuss the possibility of intra-exonic recombination or gene conversion (21 -23). Relevant multi-locus haplotype data from Siberian populations (24) are briefly mentioned. Finally, we provide short comments on MHC-mediated thymic selection in T cell repertoire and some perspectives for the HLA study.…”