Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature

Mukherjee, Souvik ; Sarkar-Roy, Neeta ; Wagener, Diane K. ; Majumder, Partha P. (2009) Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature Proceedings of the National Academy of Sciences, 106 (17). pp. 7073-7078. ISSN 0027-8424

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Official URL: http://www.pnas.org/content/106/17/7073.full

Related URL: http://dx.doi.org/10.1073/pnas.0811357106

Abstract

We tested the opposing views concerning evolution of genes of the innate immune system that (i) being evolutionary ancient, the system may have been highly optimized by natural selection and therefore should be under purifying selection, and (ii) the system may be plastic and continuing to evolve under balancing selection. We have resequenced 12 important innate-immunity genes (CAMP, DEFA4, DEFA5, DEFA6, DEFB1, MBL2, and TLRs 1, 2, 4, 5, 6, and 9) in healthy volunteers (n = 171) recruited from a region of India with high microbial load. We have compared these data with those of European-Americans (EUR) and African-Americans (AFR). We have found that most of the human haplotypes are many mutational steps away from the ancestral (chimpanzee) haplotypes, indicating that humans may have had to adapt to new pathogens. The haplotype structures in India are significantly different from those of EUR and AFR populations, indicating local adaptation to pathogens. In these genes, there is (i) generally an excess of rare variants, (ii) high, but variable, degrees of extended haplotype homozygosity, (iii) low tolerance to nonsynonymous changes, (iv) essentially one or a few high-frequency haplotypes, with star-like phylogenies of other infrequent haplotypes radiating from the modal haplotypes. Purifying selection is the most parsimonious explanation operating on these innate immunity genes. This genetic surveillance system recognizes motifs in pathogens that are perhaps conserved across a broad range of pathogens. Hence, functional constraints are imposed on mutations that diminish the ablility of these proteins to detect pathogens.

Item Type:Article
Source:Copyright of this article belongs to National Academy of Sciences, USA.
Keywords:Extended Haplotype Homozygosity; Haplotype Networks; Neutrality Tests; Resequencing
ID Code:21364
Deposited On:20 Nov 2010 13:02
Last Modified:17 May 2016 05:35

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