Molecular Evolution of the Toll-Like Receptor Multigene Family in Birds
Molecular Evolution of the Toll-Like Receptor Multigene Family in Birds
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DOI：
10.1093/molbev/msq351
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发表时间：
2011-05-01
影响因子：
10.7
通讯作者：
Edwards, Scott V.
中科院分区：
文献类型：
--
作者：
Alcaide, Miguel;Edwards, Scott V.
Toll样受体（TLR）是先天免疫系统的膜结合传感器，其识别入侵微生物的不变和独特的分子特征，并且对于启动脊椎动物的适应性免疫也是必需的。TLR基因的遗传变异与人类和牲畜中不同的病原体结果直接相关。尽管如此，新的见解TLRs的多态性对传染病的进化生态学的影响，可以通过调查尚未详细调查的其他脊椎动物群体。在这项研究中，我们进行了整个TLR多基因家族（N = 10个基因）在非模式鸟类物种的第一个表征。使用针对保守编码区的引物，我们的目的是扩增大片段的胞外结构域（275-435 aa）参与病原体识别在7个不同的鸟类物种。我们的分析表明，鸟类TLR主要由稳定的选择，这表明，非同义替换的速度慢，有助于保护生物功能。总体而言，每个TLR基因座的ω平均值（= d（n）/d（s））范围为0.196至0.517。然而，我们也发现了积极选择作用于特定氨基酸位点的模式，这些位点可能与病原体相关分子模式识别中的物种特异性差异有关。分析的2，875个密码子中只有39个（类似于1.35%）表现出显著的正选择模式。这些积极选择的密码子中至少有一半可以映射到推定的配体结合区域，如TLR及其配体的晶体结构和诱变分析所示。我们还调查了TLR多态性在野生种群的两种鸟类，小红隼Falco naumanni和家雀Carpodacus墨西哥。一般来说，鸟类TLR显示低至中度的单核苷酸多态性水平和过量的沉默核苷酸取代，但也明显的正向选择的情况。特别是，TLR 5和TLR 15表现出最高程度的遗传多态性和最高发生率的非保守氨基酸取代。这项研究提供了关键的引物和第一次看到的进化模式和TLR多态性在非模式鸟类物种的影响，并扩展了鸟类生态免疫遗传学的候选位点的名单以外的广泛采用的基因的主要组织相容性复合体（MHC）。
Toll-like receptors (TLR) are membrane-bound sensors of the innate immune system that recognize invariant and distinctive molecular features of invading microbes and are also essential for initiating adaptive immunity in vertebrates. The genetic variation at TLR genes has been directly related to differential pathogen outcomes in humans and livestock. Nonetheless, new insights about the impact of TLRs polymorphism on the evolutionary ecology of infectious diseases can be gained through the investigation of additional vertebrate groups not yet investigated in detail. In this study, we have conducted the first characterization of the entire TLR multigene family (N = 10 genes) in non-model avian species. Using primers targeting conserved coding regions, we aimed at amplifying large segments of the extracellular domains (275-435 aa) involved in pathogen recognition across seven phylogenetically diverse bird species. Our analyses suggest avian TLRs are dominated by stabilizing selection, suggesting that slow rates of nonsynonymous substitution help preserve biological function. Overall, mean values of omega (= d(n)/d(s)) at each TLR locus ranged from 0.196 to 0.517. However, we also found patterns of positive selection acting on specific amino acid sites that could be linked to species-specific differences in pathogen-associated molecular pattern recognition. Only 39 of 2,875 (similar to 1.35%) of the codons analyzed exhibited significant patterns of positive selection. At least one half of these positively selected codons can be mapped to putative ligand-binding regions, as suggested by crystallographic structures of TLRs and their ligands and mutagenic analyses. We also surveyed TLR polymorphism in wild populations of two bird species, the Lesser Kestrel Falco naumanni and the House Finch Carpodacus mexicanus. In general, avian TLRs displayed low to moderate single nucleotide polymorphism levels and an excess of silent nucleotide substitutions, but also conspicuous instances of positive directional selection. In particular, TLR5 and TLR15 exhibited the highest degree of genetic polymorphism and the highest occurrence of nonconservative amino acid substitutions. This study provides critical primers and a first look at the evolutionary patterns and implications of TLR polymorphism in non-model avian species and extends the list of candidate loci for avian eco-immunogenetics beyond the widely employed genes of the Major Histocompatibility Complex (MHC).