Positive selection on mammalian MHC-DQ genes revisited from a multispecies perspective

Abstract

Major histocompatibility complex class II DQA and DQB genes have been shown to be under positive selection in certain mammalian species but not in others, fuelling a debate about how their polymorphism has evolved. In this study, we have analysed whether polymorphism in the peptide-binding region (PBR) of DQA (190 sequences, 11 species) and DQB (209 sequences, 7 species) molecules is positively selected by using both approximate (Nei-Gojobori, Li-Wu-Luo and Pamilo-Bianchi-Li) and maximum-likelihood methods. The results obtained with approximate methods were rather inconsistent for DQA, probably due to the high inaccuracy with which d S (PBR) is estimated, whereas evidence of positive selection was observed for most of the DQB PBR sequences. A parallel analysis with CodeML allowed us to demonstrate, in a very consistent way, the occurrence of positive selection in the PBR-encoding region of both DQA and DQB genes. Moreover, we have identified several DQA (a47, a55, a56, a68, a69, a76 and a79) and DQB (b9, b26 and b57) codons that appear to be under positive selection in different, and often unrelated, mammalian species. Non-synonymous polymorphism at these sites has been evolutionarily conserved meaning that it might have functional consequences on peptide binding.

Genetic diversity and differentiation of the rhesus macaque (Macaca mulatta) population in western Sichuan, China, based on the second exon of the major histocompatibility complex class II DQB (MhcMamu-DQB1) alleles

“…The ABS and non-ABS were distinguished based on HLA-DQB1 structure [74]. Phylogenetic trees were reconstructed for Mhc-DQB1 allelic sequences using Mega 5.05, based on the neighbor-joining method with Kimura 2-para model.…”

MHC class II DQA gene variation across cohorts of brown hares (Lepus europaeus) from eastern Austria: Testing for different selection hypotheses

“…We focused on the exon 2 which encodes part of the peptide binding region (PBR) and is the most polymorphic part of this gene. There is evidence that the DQA gene is under positive selection also in other studied mammals, apparently mediated by parasites (Waine et al, 1998;Bryja et al, 2006;Cutrera and Lacey, 2006;Amills et al, 2008;Deter et al, 2008). DQA genotyping and screening is described in detail in Goüy de .…”

Natural selection coupled with intragenic recombination shapes diversity patterns in the major histocompatibility complex class II genes of the giant panda

“…Although the Z-test might underestimate selection intensity compared with the maximum-likelihood method (Amills et al, 2008), the latter is unsuitable for cases with recombination events (Wilson and McVean, 2006), and the Z-test can give an idea of the intensity of positive and purifying selection. Our results showed that DRB3 and DQA1 were subject to the same selection mechanism in both subspecies (Table 8), with strong positive selection of the DRB3 gene and weak positive (at ABS) and purifying (at non-ABS) selection of DQA1.…”

“…The classic a and b genes are extremely polymorphic, especially at the antigen-binding sites (ABS) in exon2 (Reche and Reinherz, 2003;Furlong and Yang, 2008). The remarkable polymorphism of MHC genes is believed to be driven by positive selection (Hughes and Yeager, '98;Richman, 2000;Bernatchez and Landry, 2003;Sommer, 2005;Amills et al, 2008) as the host is subject to a wide range of infections by diverse environmental pathogens. Positive selection often involves balancing selection achieved through heterozygote advantage (overdominant selection) and frequency-dependent selection (Takahata and Nei,'90).…”