title: Evolutionary analysis for functional divergence of the toll-like receptor gene family and altered functional constraints.
abstract: The Toll-like receptor (TLR) gene family consists of type 1 transmembrane receptors, which play essential roles in both innate immunity and adaptive immune response by ligand recognition and signal transduction. Using all available vertebrate TLR protein sequences, we inferred the phylogenetic tree and then characterized critical amino acid residues for functional divergence by detecting altered functional constraints after gene duplications. We found that the extracellular domain of TLR genes showed higher functional divergence than that of the cytoplasmic domain, particularly in the region between leucine-rich repeat (LRR) 10 and LRR 15 of TLR 4. Our finding supports the concept that sequence evolution in the extracellular domain may be responsible for the broad diversity of TLR ligand-binding affinity, providing a testable hypothesis for potential targets that could be verified by further experimentation.
authors.affiliation: Department of Genetics, Development and Cell Biology, Center for Bioinformatics and Biological Statistics, Iowa State University, 332 Science II Hall, Ames, IA 50011, USA.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Zhou
authors.forename: Jianying
authors.initials: J
authors.lastname: Gu
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Lamont
authors.forename: Xun
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D030562:Databases, Protein; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D005810:Multigene Family; D010802:Phylogeny; D051193:Toll-Like Receptors / Q000145:classification / Q000235:genetics*
chemical_list: D051193:Toll-Like Receptors