Adaptive evolution of the IgA hinge region in primates.
IgA is a major component that prevents the penetration of pathogenic bacteria into mucosal surfaces. The IgA antibody is cleaved at the IgA hinge region with high specificity by IgA-specific proteases produced by several pathogenic bacteria. We conducted a genomic sequence analysis of the IgA genes of a wide spectrum of primates, including the first intron and second exon, which consist of the hinge region and the CH2 domain, to find evidence of positive selection. Because the hinge region is quite small, we combined the largest collection of sequences that could be clearly aligned and evaluated the total numbers of synonymous and nonsynonymous substitutions on the phylogenetic tree. The nonsynonymous to synonymous substitution ratio (d(N)/d(S) test) showed that hominoids, Old World monkeys, and New World monkeys have d(N)/d(S) ratios of 5.4, 6.3, and 4.2, respectively. Fisher's exact probability tests showed statistical significance for the Old World monkey. Because the substitution rates of the flanking sequences are more or less similar to the synonymous rates of the hinge region, these high values of d(N)/d(S) should be the result of positive selection at the hinge region. Combining the high sequence variability in each population and the highly accelerated nonsynonymous substitution rates in the hinge region, we conclude that this unusual IgA evolution is a molecular evidence of adaptive evolution possibly caused by the host-parasite relationship.
Sumiyama
Kenta
K
Department of Biological Sciences, Graduate School of Science, University of Tokyo. Laboratory of Evolutionary Genetics, National Institute of Genetics, Mishima 411-8540, Japan. kenta.sumiyama@yale.edu
Saitou
Naruya
N
Ueda
Shintaroh
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D019143:Evolution, Molecular; D005091:Exons; D014644:Genetic Variation; D052058:Hinge Exons; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011323:Primates / Q000235:genetics*; D012641:Selection, Genetic
D017931:DNA Primers; D007070:Immunoglobulin A