HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3′UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.
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We thank Dr Simone Kashima, Sandra Rodrigues, Rochele Azevedo, Evandra Strazza Rodrigues and Adriana Marques for technical assistance. We thank Cynthia Maria de Campos Prado Manso and Elettra Greene for assistance with the English language. This study was supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brazil) grant 475670/2007-8, CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) grant 2013/19382-0 and FAEPA (Fundação de Apoio ao Ensino, Pesquisa e Assistência do HCFMRP-USP). CTM-J was supported by post-doctoral fellowships from CNPq/Brazil (150996/2005-5) and from FAPESP/Brazil (07/58391-4), and is currently supported by a Research fellowship from CNPq/Brazil (305493/2011-6). ECC was supported by a post-doctoral fellowship from FAPESP/Brazil (07/58420-4).
The authors declare no conflict of interest.
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Mendes-Junior, C., Castelli, E., Meyer, D. et al. Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection. Genes Immun 14, 518–526 (2013). https://doi.org/10.1038/gene.2013.47
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