Population genetics of immune function genes: a study of Amerindian populations

Author(s)

Márcia Regina Pincerati

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2011-08-02

Examining board members

Diogo Meyer; Anna Carla Renata Krepel Goldberg; Regina Celia Mingroni Netto; Eduardo Jose Melo dos Santos; Tatiana Teixeira Torres

• Advisor: Diogo Meyer

Abstract

The diversity of several genes has been explained by the action of natural selection. Among them, the immune system genes are highlighted. In addition, several studies have demonstrated the action of selective pressure modulating the diversity of regulatory regions. Amerindian populations have a relatively recent evolutionary history, with remarkable demographic processes and new environmental challenges with different selection pressures. Therefore, those populations are excellent candidates for studies of natural selection. In order to broaden the knowledge of how natural selection has been acting in human populations, this study proposed a population analysis of three loci, previously characterized as targets of selection in Amerindian populations: two from the KIR complex (KIR2DL4 and KIR3DL1/S1) and regulatory regions of HLA-G. Evidence of action of balancing selection in Amerindian populations was found for KIR2DL4 and KIR3DL1/S1 genes. For KIR3DL1/S1 gene were observed evidences of natural selection acting on two different levels of variation: (1) absence and presence of KIR3DL1 and KIR3DL1/S1 allotypes and (2) maintenance of different strains of KIR3DL1 allotype. Correlations between the diversity of KIR2DL4 and autosomal markers show that the demographic processes have an important role in modulating the genetic variation observed in these populations, but do not explain all the variation patterns found. The results of analysis of promoter regions and 3\'UTR of the HLA-G gene revealed evidence of balancing selection acting at the promoter region in Amerindian populations and at the 3\'UTR region in a European population. Furthermore, the analysis of these two regions together showed that t both are highly related and divergent haplotypes at high frequency were found, which may be related to different regulatory activities to maintain a balance of high and low expression of the gene. Analyses of SNPs found in the regulatory regions of HLA-G were not associated with differences in expression levels of the molecule. Together, these results suggest that the effetcs (AU)