Native populations in South American: a multi-locus study of demographic and selective history

Author(s)

Kelly Nunes

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2011-12-12

Examining board members

Diogo Meyer; Maria Luiza Petzl Erler; Nelson Jurandi Rosa Fagundes; Tatiana Teixeira Torres

• Advisor: Diogo Meyer

Abstract

The present study addresses two main themes: a) demographic history of the Native American populations and b) how the demographic and selective history shapes the diversity and differentiation of the HLA genes on those populations. The Native American populations present a peculiar evolutive history, with demographic pattern that are distinct from other populations in the world. Previous studies suggest that they have: a) low genetic diversity and high inter-populational diversity compared to the other world populations; b) a diversity decreasing gradient on the north-south direction of the American continent; c) high levels of genetic variability between populations that live in the western South American region, compared with the eastern ones. However, these findings are based on studies that present a sampling deficiency for the Amerindian populations located on the Amazon River lowlands. On the present study we suppress this deficiency by analyzing 11 populations of the Amazon River lowlands and 3 populations of the Brazilian South-Center. We have observed that: a) the populations of the East and West of the South America are highly differentiated, in accordance with previous studies; b) the differentiation among the Eastern South America is greater than among the Western ones (Andean region and Northwestern South America) agreeing with previous studies; c) the larger differentiation among the Eastern South American populations is caused by specific groups (Ache, Arara do Iriri, Araweté, Suruí and Ticuna Tarapaca), which present peculiar evolutive histories; d) analysis that exclude these high differentiation level populations shows that for the remaining group, the differentiation level of the Eastern regions is similar to the differentiation levels found on the Western regions of the South American continent, corroborating the morphological studies; e) the east of the South America is divided in two distinct populational groups (Amazon Southwest and the Amazon East/South Central of South America) and with different genetic ancestry (the Amazon West with greater genetic component form the Northwestern South America and the Amazon East/South Central with greater Andean genetic component), agreeing with the migration routes model proposed by SCHMITZ, 1983. The HLA genes, located on the MHC region, are involved on the adaptative immune response and have the function of presenting peptides on the cellular surface. Various studies show that the HLA genes are evolving under balancing selection. The genetic variability profile of the HLA genes on the Native American populations (with great number of alleles and some with a frequency very distinct from other world regions) differs from the other genes so far analyzed in these population. On the present study we investigate the contributions of the demographic history on shaping the genetic variability of the regions adjacent to the HLA genes on Native-American populations. To accomplish that, we compared the profile of 16 microsatellites of the MHC region with 61 microsatellites spread through the genome (demographic control) in 28 Native American populations, 1 African population (Ovimbundu) and 1 European population (Portuguese). We observed that: a) the microsatellites of the MHC region present a high linkage disequilibrium among themselves, corroborating previous studies; b) present higher inter-populational differentiation than the microsatellites spread through the genome. This signal is opposed to the ones we expected from genes that are evolving under balancing selection. Previous studies show that even populations composed by groups of distinct HLA alleles present low levels of differentiation. We suggest that the selection could be favoring specific allele (or allele group) in different geographic regions, and since the populational differentiation indexes such as FST estimate the variance of the allelic frequencies, it would be \"blind\" to the difference on the allelic composition of the populations. As a case study, e investigate the HLA-B gene, which, in the American native populations, present a group composed by endemic allele and alleles that occur in high frequency on the American continent and in low frequency outside of it. With the intention of verifying if there are signs of selection on the regions adjacent to this gene, we have analyzes 6 microsatellites flanking to the HLA-B in 28 native populations. We estimated the heterozygosis of the microsatellites associated to a determined HLA-B allele as well as the degree of association of the microsatellite alleles with the HLA-B lineage and alleles. The analysis showed that: a) in general, the heterozygosis associated to the endemic alleles is similar to the one observed in cosmopolitan alleles (with exception of the HLA-B∗3909 and B∗3543); b) the differentiation observed from the adjacent microsatellites is greater between the HLA-B lineages than inside the lineages; c) specific microsatellites haplotypes present strong association with the HLA-B lineages. These results are surprising since the HLA-B lineages have existed even before the human speciation. We suggest that the low heterozygosis associated to the lineages could be related to two factors: a) the populational bottleneck occurred during the modern human entrence on the American continent; b)selection acting on the favoring, not only of the alleles, but also on the HLA-B lineages. In conclusion, despite the intense demographic history, the Native American populations present signs of selective forces acting on the MHC region (AU)