Molecular evolution of α4 integrin binding site to lentiviral envelope proteins in new world primates

Integrin epitopes encoded by ITGA4 exons 5 and 6 encompass the α4β7 binding site to natural ligands and HIV-1 gp120. Functional assays of α4 variants of new world primates (NWP) showed reduced binding of several ligands, including the HIV-1 envelope, probably accounting for restriction phenotypes conferring resistance to lentiviral infection (Darc et al., 2011). In this paper, we have analyzed, by cloning and sequencing, the α4 domain polymorphisms present in 10 NWP species and four old world primates (including human). Analyses of differential selection at codon sites and along evolutionary lineages were carried out. We identified codons under positive selection, including polymorphic variations at codon 201, presumably convergent during NWP radiation and significant positive selection leading to a single allele (SagVar2).