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High frequencies of alleles MICA*020 and MICA*027 in Amerindians and evidence of positive selection on exon 3

Genes & Immunity volume 9, pages 697–705 (2008)Cite this article

Abstract

MICA is a nonclassical polymorphic MHC molecule. We investigated MICA allelic frequencies and MICA–HLA-B–HLA-C haplotypes in Brazilian Amerindians to describe the polymorphism and to extract information about the evolution of MICA gene. Kaingang is the first population described to have a high frequency of MICA*020, found associated with HLA-B*3505–HLA-Cw*0401. Allele MICA*020 probably originated de novo in South America. The Guarani population had high frequencies of MICA*027. Allele MICA*00801 is common worldwide but rare among Amerindians, occurring only because of gene flow. The analysis of the 64 described MICA alleles revealed that in exons 2 and 4, synonymous substitutions are in excess, a result compatible with purifying selection. The opposite was observed for exons 3 and 6 and the excess of nonsynonymous substitutions was significant for exon 3, indicating positive selection. Few of the alleles described so far had exon 6 sequenced, impeding conclusions for the corresponding portion of the molecule. The analysis of the entire gene is required for a better understanding of the evolution of MICA's polymorphism and its functional consequences. This knowledge is of prime importance in view of the increasing awareness of the functional and medical implications of MICA gene variability.

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Acknowledgements

We thank the individuals of the populations analyzed in this research for their collaboration. The support and friendship of our laboratory colleagues are highly valued. We are also grateful for the support of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Institutos do Milênio, Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná, Fundação da Universidade Federal do Paraná (FUNPAR) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Departamento de Genética, Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    L A Oliveira, L T Tsuneto & M L Petzl-Erler

  2. Departamento de Genética, Laboratório de Imunogenética e Histocompatibilidade, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

    F Ribas & M G Bicalho

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  1. L A Oliveira
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Correspondence to M L Petzl-Erler.

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Oliveira, L., Ribas, F., Bicalho, M. et al. High frequencies of alleles MICA*020 and MICA*027 in Amerindians and evidence of positive selection on exon 3. Genes Immun 9, 697–705 (2008). https://doi.org/10.1038/gene.2008.65

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