Toll-like receptors (TLRs) play an important role for the innate immune system by detecting pathogen-associated molecular patterns. TLR5 encodes the major extracellular receptor for bacterial flagellin and frequently evolves under positive selection, consistent with coevolutionary arms races between the host and pathogens. Furthermore, TLR5 is inactivated in several vertebrates and a TLR5 stop codon polymorphism is widespread in human populations. Here, we analyzed the genomes of 120 mammals and discovered that TLR5 is convergently lost in four independent lineages, comprising guinea pigs, Yangtze river dolphin, pinnipeds, and pangolins. Validated inactivating mutations, absence of protein-coding transcript expression, and relaxed selection on the TLR5 remnants confirm these losses. PCR analysis further confirmed the loss of TLR5 in the pinniped stem lineage. Finally, we show that TLR11, encoding a second extracellular flagellin receptor, is also absent in these four lineages. Independent losses of TLR5 and TLR11 suggest that a major pathway for detecting flagellated bacteria is not essential for different mammals and predicts an impaired capacity to sense extracellular flagellin.

中文翻译：

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TLR5的趋同丢失表明在四个哺乳动物谱系中胞外鞭毛蛋白检测的改变。

Toll样受体（TLR）通过检测病原体相关的分子模式在先天免疫系统中起重要作用。TLR5编码细菌鞭毛蛋白的主要细胞外受体，并经常在阳性选择下进化，这与宿主和病原体之间的协同进化军备竞赛一致。此外，TLR5在一些脊椎动物中是失活的，并且TLR5终止密码子多态性在人群中很普遍。在这里，我们分析了120种哺乳动物的基因组，发现TLR5在四个独立的谱系中逐渐消失，其中包括豚鼠，长江豚，nip和穿山甲。验证的失活突变，不存在蛋白编码的转录表达以及对TLR5残基的轻松选择都证实了这些损失。PCR分析进一步证实了在夹入的茎谱系中TLR5的丢失。最后，我们显示在这四个谱系中也没有编码第二种细胞外鞭毛蛋白受体的TLR11。TLR5和TLR11的独立丧失表明，检测鞭毛细菌的主要途径对于不同的哺乳动物而言不是必需的，并且预示着感知细胞外鞭毛蛋白的能力将受损。