title: Increased positive selection pressure within the complementarity determining regions of the T-cell receptor β gene in New World monkeys.
abstract: Because of the long-term co-evolution of TCR and MHC molecules, numerous nucleotide substitutions have accumulated within the domains of TCRβ genes. We previously found that nonsynonymous nucleotide substitutions occurred more frequently in complementarity determining region (CDR)β than in CDRα, even though only a limited number of common marmoset (Callithrix jacchus) and human T-cell receptor β variable (TRBV) sequences were compared. This interesting finding raised the question of whether the increased selective pressure within CDRβ was species-specific. In this study, we identified 21 TRBV region sequences from the common marmoset and performed comparative sequence analyses of the T-cell receptor α variable (TRAV) and TRBV regions from human, chimpanzee, rhesus monkey, cotton-top tamarin, Ma's night monkey, and common marmoset. The ratios of the number of nonsynonymous nucleotide substitutions per site (d(N) ) to the d(S) values (d(N) /d(S) ) were less than 1 within the framework regions (FRs) of TRAV and TRBV region sequences, suggesting that purifying selection is largely dominant within the FRs. In contrast, the d(N) values were statistically significantly greater for CDRβ than for CDRα only in New World monkeys. Also, increased d(N) /d(S) ratios (d(N) /d(S) >1) were observed within CDRβ between humans and New World monkeys and, interestingly, between New World monkeys, which share a relatively recent common ancestor. Moreover, phylogenetic analysis by maximum likelihood analysis provided firm evidence to support that positive selection occurred within CDRβ along New World monkey lineages. These results suggest that increased positive selection pressure within CDRβ is common in New World monkeys rather than being species-specific. This study provides an intriguing insight into the co-evolution of TCR and MHC molecules within primates.
authors.affiliation: Laboratory of Immune Regulation, Wakayama Medical University, Osaka, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Matsutani
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kitaura
authors.forename: Satsuki
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tsuruta
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Takasaki
authors.forename: Kouetsu
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D051079:Catarrhini / Q000235:genetics; D022801:Complementarity Determining Regions / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D051078:Platyrrhini / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D022801:Complementarity Determining Regions