[Molecular evolution of MHC DQA genes. I. The maintenance of interallelic divergence and the influence of GC content on gene structure].
The analyses of the proportion of synonymous and missense nucleotide substitution (PS and PN) in different exons, antigen recognition sites (ARS) and non-ARS of EN2 (NAEN2) of 23 alleles at MHC DQA loci in 7 mammal species gave rise to the following findings. (1) PN was about twice as much as PS in ARS among the alleles at DQA1 of any given species, i.e. 7 alleles at HLA-DQA1 or 8 alleles at IaAa this accords with overdominant selection; (2) PS showed more or less the same as PN in ARS among different loci (DQA1 or DQA2 in different species, or DQA1 and DQA2 in one species) or NAEN2 of all comparative pairs, this conforms the expectation of neutral selection; (3) In exon4 and exon3, not only was the substitution proportion extremely low, but also PS was much higher than PN (the ratio PS over PN is 19.5 in alleles at IaAa of mouse and 4 among alleles at different loci), this coincides obviously with purification selection. The analysis of GC content of MHC DQA showed that its peaks were in the regions corresponding to the middle bulks of some domains, that the highest and constant level was in exon4 and that GC content in the third codon position (GC III content) associates inversely with PS. These results indicate that the specified maintenance mechanisms of interallelic diversity relevant to their functions exist in given exons corresponding to some domains of the same MHC DQA locus and GC III content is an important factor in keeping the structure and function of gene under selection constraint. The method for estimating nucleotide substitution proportion was modified.
Pan
X
X
Department of Biology, Second Military Medical University Shanghai.
Fu
J
J
D000483:Alleles; D000818:Animals; D001482:Base Composition; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006801:Humans
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen