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Genes and Immunity (2008) 9, 651658 & 2008 Macmillan Publishers Limited All rights reserved 1466-4879/08 $32.00 http://www.nature.com/gene
Web End =www.nature.com/gene
1Departament de Cincia Animal i dels Aliments, Facultat de Veterinria, Universitat Autnoma de Barcelona, Bellaterra, Spain;
2Unitat de Biologia Evolutiva, Departament de Cincies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain;
3Institute of Genetics, Vetsuissefaculty, University of Berne, Berne, Switzerland and 4Departament de Biologia, Facultat de Cincies, Universitat de Girona, Girona, Spain
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 (NeiGojobori, LiWuLuo and PamiloBianchiLi) and maximum-likelihood methods. The results obtained with approximate methods were rather inconsistent for DQA, probably due to the high inaccuracy with which dS (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. Genes and Immunity (2008) 9, 651658; doi:http://dx.doi.org/10.1038/gene.2008.62
Web End =10.1038/gene.2008.62 ; published online 7 August 2008
Keywords: positive selection; DQA; DQB; major histocompatibility complex
One of the most distinctive features of MHC genes is that their polymorphism is maintained by positive selection as a way to increase the repertoire of antigen-presenting molecules on cell surface.1,2 The genetic
signature that positive selection leaves on MHC genes consists of an increased ratio (w dN/dS) between non-synonymous substitutions per non-synonymous site (dN)
and synonymous substitutions per synonymous site (dS)
inside the PBR (w41) but not outside (no-PBR region, wp1).1,2 This central concept has been sufficiently demonstrated for MHC class I...