Abstract
Duplication of genes has been thought as a major resource for the function innovation in a large number of gene families. The prediction of critical residues for functional divergence between homologous genes is important for functional genomics. The Toll-like receptor (TLR) gene family plays an important role in innate immunity and adaptive immune response. All TLR protein sequences from vertebrate animals were collected to investigate functional divergence and evolutionary pattern between TLR gene clusters. Four independent clusters were identified. Functional divergence of the domains in TLR family was characterized by a site-specific posterior profile analysis, and critical residues for altered selective constraints of amino acid sites after gene duplication were predicted. The extracellular domain of TLR gene showed higher functional divergence than the cytoplasmic domain. Further analysis indicated that the region between Leucine-rich repeats (LRR) 10 and 14 of TLR4 was a potential target for functional genomics study in the future. For a large set of gene families study, we collected the cDNA sequences of all orthologous genes of human, mouse or rat of two-gene cluster, three-gene cluster, and four-gene cluster from all available gene families in the database. The nonsynonymous and synonymous substitutions rate for all orthologs between human and mouse or rat were estimated. The ratio of nonsynonymous to synonymous substitutions rate were calculated. The nonsynonymous substitutions rate was positively correlated with synonymous substitutions rate, and the ratio of nonsynonymous to synonymous substitutions rate, which suggested that nonsynonymous substitutions rate is a major resource of the ratio of nonsynonymous to synonymous substitutions rate. The significant differences of nonsynonymous substitutions rate in most of paralogous genes suggested that nonsynonymous substitution plays an important role in creating novel function following gene duplication.