Coevolution of the vertebrate integrin alpha- and beta-chain genes.
The integrin receptors are heterodimers whose alpha and beta subunits are encoded by separate, evolutionarily unrelated multigene families. Phylogenetic analysis of DNA sequences from these two gene families showed that they have not always evolved in a parallel fashion. The integrin alpha chains that can form heterodimers with beta 1 do not constitute a monophyletic group, nor do the beta chains which can form heterodimers with alpha V. On the other hand, the vertebrate alpha chains associating with beta 2 are a monophyletic group. In the metal cation-binding region of the alpha chain, an exon exchange took place between human alpha M and alpha X approximately 40-50 Mya, homogenizing this functionally important region in these two alpha chains. When integrin beta chains of different functional classes are compared, nonsynonymous (amino acid altering) nucleotide substitutions that alter amino acid residue charge in the central region of the molecule occur at a rate significantly higher than that expected under random replacement. By contrast, when closely related beta 1 chains are compared, residue charge is conserved in this region. These results pinpoint the central region as a focus of functional divergence among integrin beta chains, perhaps relating to the ability of each beta integrin class to associate with a specific array of alpha integrins. Furthermore, they imply that positive, directional selection on this region has occurred in the evolution of the integrin beta-chain gene family.
Hughes
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Department of Biology and Institute of Molecular Evolutionary Genetics, Pennsylvania State University, University Park 16802.
D000818:Animals; D001482:Base Composition; D005075:Biological Evolution; D004563:Electrochemistry; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D007700:Kinetics; D005810:Multigene Family; D010802:Phylogeny; D011995:Recombination, Genetic; D012641:Selection, Genetic; D014714:Vertebrates / Q000235:genetics
D016023:Integrins