Sequence and Structural Characterization of Toll-Like Receptor 6 from Human and Related Species

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.