Global Footprints of Purifying Selection on Toll-Like Receptor Genes Primarily Associated with Response to Bacterial Infections in Humans
| Autor: | Partha P. Majumder, Souvik Mukherjee, Debdutta Ganguli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Nonsynonymous substitution
haplotype Population innate immune system Biology Evolution Molecular Negative selection evolution Genetics Humans Protein Footprinting Selection Genetic education Gene Ecology Evolution Behavior and Systematics Alleles Toll-like receptor education.field_of_study Innate immune system Natural selection Polymorphism Genetic Haplotype Toll-Like Receptors Bacterial Infections Sequence Analysis DNA Immunity Innate Genetics Population Haplotypes Genetic Loci Host-Pathogen Interactions Indian populations purifying selection Research Article |
| Zdroj: | Genome Biology and Evolution |
| ISSN: | 1759-6653 |
| Popis: | Toll-like receptors (TLRs) are directly involved in host–pathogen interactions. Polymorphisms in these genes are associated with susceptibility to infectious diseases. To understand the influence of environment and pathogen diversity on the evolution of TLR genes, we have undertaken a large-scale population-genetic study. Our study included two hunter–gatherer tribal populations and one urbanized nontribal population from India with distinct ethnicities (n = 266) and 14 populations inhabiting four different continents (n = 1,092). From the data on DNA sequences of cell-surface TLR genes, we observed an excess of rare variants and a large number of low frequency haplotypes in each gene. Nonsynonymous changes were few in every population and the commonly used statistical tests for detecting natural selection provided evidence of purifying selection. The evidence of purifying selection acting on the cell-surface TLRs of the innate immune system is not consistent with Haldane’s theory of coevolution of immunity genes, at least of innate immunity genes, with pathogens. Our study provides evidence that genes of the cell-surface TLRs, that is, TLR2 and TLR4, have been so optimized to defend the host against microbial infections that new mutations in these genes are quickly eliminated. |
| Databáze: | OpenAIRE |
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