Diversifying and Purifying Selection in the Peptide Binding Region of DRB in Mammals

Abstract

The class II genes of the major histocompatibility complex encode proteins which play a crucial role in antigen presentation. They are among the most polymorphic proteins known, and this polymorphism is thought to be the result of natural selection. To understand the selective pressure acting on the protein and to examine possible differences in the evolutionary dynamics among species, we apply maximum likelihood models of codon substitution to analyze the DRB genes of six mammalian species: human, chimpanzee, macaque, tamarin, dog, and cow. The models account for variable selective pressures across codons in the gene and have the power to detect amino acid residues under either positive or negative selection. Our analysis detected positive selection in the DRB genes in each of the six mammals examined. Comparison with structural data reveals that almost all amino acid residues inferred to be under positive selection in humans are in the peptide binding region (PBR) and are in contact with the antigen side chains, although residues outside of but close to the PBR are also detected. Strong purifying selection is also detected in the PBR, at sites which contact the antigen and at sites which may be involved in dimerization or T cell binding. The analysis demonstrates the utility of the random-sites analysis even when structural information is available. The different mammalian species are found to share many positively or negatively selected sites, suggesting that their functional roles have remained very similar in the different species, despite the different habitats and pathogens of the species.

Adaptive Evolution of Formyl Peptide Receptors in Mammals

“…Thus, minor differences in the tree topology have little impact on our inference of positive selection under site models. Similar robustness of the site model analysis to the tree topology was also reported in other studies (Furlong and Yang 2008;Yang and Swanson 2002).…”

cDNA cloning and polymorphic domains of the major histocompatibility complex (MHC) class I in two Chinese native chicken breeds

“…This was similar to the mammalian MHC class II DRB, even as Furlong and Yang (2008) found that almost all amino acid residues inferred to be under positive selection were in the PBD and in contact with the antigen side chains, although residues outside of but close to the PBD. In the evolution process, mutation of the amino acid sequence occurs in the non-PBD, destroying PBD structure integrity which makes MHC molecules fail in binding antigen peptides, while some mutations within the PBD increase the potential of MHC binding antigen peptides.…”

“…This kind of polymorphism is the result of natural selection (Furlong and Yang, 2008). In mammals, MHC gene region spans approximately 4 Mb, while in avian it is greatly reduced in size and gene content (Kaufman et al, 1999).…”

“…Fax: 0086-551-5786013. and Yang, 2008;O'Leary et al, 2009), whales (Xu et al, 2009) wild animals (Koutsogiannouli et al, 2009;Becker et al, 2009) and avian (Ewald and Livant, 2004;Westerdahl et al, 2000).…”

Sexual selection explains more functional variation in the mammalian major histocompatibility complex than parasitism

“…However, these predicted sites were strongly and significantly correlated with the 15 peptide-binding region residues determined based on protein crystallography (Pearson's correlation ranged from r(29) ¼ 0.49, p , 0.01, primates, to r(12) ¼ 0.93, p , 0.001, rodents). In addition, these 15 sites are known to be involved with antigen binding and have been shown to be under positive selection across a diverse set of taxa (carnivores, rodents and primates [41]; bats [42]). Therefore, we focus analyses on these documented 15 ABS sites, though analyses with putative taxonspecific ABS sites show overall consistent results (see the electronic supplementary material, figure S3).…”