Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region.

Autor:	Vargas LB; Programa de Pós-Graduação em Genética, Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brazil., Beltrame MH; Programa de Pós-Graduação em Genética, Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brazil., Ho B; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA., Marin WM; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA., Dandekar R; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA., Montero-Martín G; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA., Fernández-Viña MA; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA., Hurtado AM; School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA., Hill KR; School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA., Tsuneto LT; Departamento de Análises Clínicas, Universidade Estadual de Maringá, Maringá, PR, Brazil., Hutz MH; Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Salzano FM; Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Petzl-Erler ML; Programa de Pós-Graduação em Genética, Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brazil., Hollenbach JA; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Augusto DG; Programa de Pós-Graduação em Genética, Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brazil.; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Jazyk:	angličtina
Zdroj:	Molecular biology and evolution [Mol Biol Evol] 2022 Jan 07; Vol. 39 (1).
DOI:	10.1093/molbev/msab298
Abstrakt:	The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR-HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR-HLA interactions among all described worldwide populations, and that 83-97% of their KIR-HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR-HLA coevolution and its impact on human health and survival. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
Databáze:	MEDLINE
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