Department of Biochemistry, Government College University, Faisalabad 38000, Pakistan.
Biomed Res Int. 2021 Apr 10;2021:5545183. doi: 10.1155/2021/5545183. eCollection 2021.
Toll-like receptors (TLRs) play an important role in the innate immune response against various pathogens. They serve as expected targets of natural selection in those species which are adapted to habitats with contrasting pathogen burdens. Till date, sufficient literature about TLRs especially TLR6 is not available. The current study was therefore planned to show evolutionary patterns of human TLRs generally and TLR6 specifically along with their conservation and diversity. The study also deals with characteristic polymorphic patterns of TLR6 in humans which are involved in serious clinical consequences. The sequence analysis of TLR6 from different mammals revealed conserved regions in the protein sequence. With respect to TLR6 evolution, human showed a close evolutionary relationship with chimpanzee and orangutans, while monkeys were appeared in a separate clade showing a distant evolutionary relationship. Old World monkeys and New World monkeys made their separate clades but both have evolved from a common ancestor. The C-terminal of human TLRs (TLR1 to TLR10) exhibited more conservation as compared to other regions. The phylogram of human TLRs showed that TLR6 is closely related to TLR1 and both TLRs shared a common ancestor with TLR10. The domain analysis has revealed that TLR1 and TLR10 have least (i.e., 4) number of leucine-rich repeat (LRR) while TLR6 contains five LRRs. Three single nucleotide polymorphisms were found in TLR6 which were found to be associated with benign. Conclusively, the current comparative sequence analyses and phylogenetic analyses provided informative insights into the process of TLR evolution in mammals. Furthermore, the polymorphism analysis would serve as a useful marker in the early detection of susceptibility and resistance against cancers and other diseases in humans.
Toll 样受体（TLRs）在针对各种病原体的固有免疫反应中发挥着重要作用。它们是适应具有不同病原体负担的栖息地的物种的自然选择的预期靶标。迄今为止，有关 TLRs 的文献，尤其是 TLR6 的文献还不够充分。因此，本研究旨在展示人类 TLRs 及其保守性和多样性的一般进化模式以及 TLR6 的进化模式。该研究还涉及涉及严重临床后果的人类 TLR6 特征性多态模式。对来自不同哺乳动物的 TLR6 进行序列分析显示蛋白质序列中存在保守区域。关于 TLR6 的进化，人类与黑猩猩和猩猩具有密切的进化关系，而猴子则属于另一个进化枝，具有较远的进化关系。旧大陆猴和新大陆猴形成了各自的进化枝，但都起源于共同的祖先。与其他区域相比，人类 TLRs（TLR1 至 TLR10）的 C 端表现出更高的保守性。人类 TLRs 的系统发育树表明 TLR6 与 TLR1 密切相关，TLR1 和 TLR10 与 TLR10 具有共同的祖先。结构域分析表明，TLR1 和 TLR10 具有最少的（即 4 个）富含亮氨酸重复序列（LRR），而 TLR6 包含 5 个 LRR。在 TLR6 中发现了三个单核苷酸多态性，与良性相关。总之，目前的比较序列分析和系统发育分析为哺乳动物 TLR 进化过程提供了有价值的见解。此外，多态性分析将成为人类对癌症和其他疾病易感性和抗性的早期检测的有用标记。
