Mukherjee Souvik, Ganguli Debdutta, Majumder Partha P
National Institute of Biomedical Genomics, Kalyani, West Bengal, India.
Genome Biol Evol. 2014 Mar;6(3):551-8. doi: 10.1093/gbe/evu032.
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.
Toll样受体（TLRs）直接参与宿主与病原体的相互作用。这些基因的多态性与传染病易感性相关。为了解环境和病原体多样性对TLR基因进化的影响，我们开展了一项大规模群体遗传学研究。我们的研究包括来自印度的两个狩猎采集部落群体和一个城市化的非部落群体，他们具有不同的种族（n = 266），以及居住在四大洲的14个群体（n = 1,092）。从细胞表面TLR基因的DNA序列数据中，我们观察到每个基因中罕见变异过多以及大量低频单倍型。每个群体中的非同义变化很少，并且用于检测自然选择的常用统计测试提供了纯化选择的证据。作用于先天免疫系统细胞表面TLRs的纯化选择证据与霍尔丹关于免疫基因（至少是先天免疫基因）与病原体共同进化的理论不一致。我们的研究提供了证据，即细胞表面TLRs的基因，即TLR2和TLR4，已经如此优化以保护宿主免受微生物感染，以至于这些基因中的新突变会迅速被消除。
