title: Comparative analysis of vertebrate PEPT1 and PEPT2 genes.
abstract: The plasma membrane transport proteins belong to SoLute Carrier 15 (SLC15) family and two members of this family have been characterized extensively in higher vertebrates, namely PEPT1 and PEPT2. Despite many efforts have made to define a pharmacophore model for efficient binding and transporting of substrates, there is not a comprehensive study performed to elucidate the evolutionary mechanisms among the SLC15 family members and to statistically evaluate sequence conservation and functional divergence between members. In this study, we compared and contrasted the rates and patterns of molecular evolution of 2 PEPT genes. Phylogenetic tree assembly with all available vertebrate PEPTs suggests that the PEPTs originated by duplications and diverged from a common protein at the base of the eukaryotic tree. Topological structure demonstrates both members share the similar hydrophobic domains (TMDs), which have been constrained by purifying selection. Although both genes show qualitatively similar patterns, their rates of evolution differ significantly due to an increased rate of synonymous substitutions in the structural domains in one copy, suggesting substantial differences in functional constraint on each gene. Site-specific profiles were established by posterior probability analysis revealing significantly divergent regions mainly locate at the hydrophobic region between predicted transmembrane domains 9 and 10 of the proteins. Thus, these results provide the evidence that several amino acid residues with reduced selective constraints are largely responsible for functional divergence between the paralogous PEPTs. These findings may provide a starting point for further experimental verifications.
authors.affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, 200240, Shanghai, People's Republic of China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Wang
authors.forename: Xiangzhe
authors.initials: X
authors.lastname: Zhang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhao
authors.forename: Qishan
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D000074011:Peptide Transporter 1; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D051381:Rats; D027981:Symporters / Q000145:classification / Q000235:genetics*
chemical_list: D000074011:Peptide Transporter 1; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2