PMID: 9169560Jun 1, 1997Paper

Coordinated amino acid changes in the evolution of mammalian defensins

Journal of Molecular Evolution
A L Hughes, M Yeager

Abstract

The mammalian defensin molecule is a short, highly cationic peptide cytotoxic to both microbial and mammalian cells which is cleaved from a precursor including a signal peptide and a highly anionic propiece. A phylogenetic analysis of 28 complete sequences from five mammalian species (mouse, rat, guinea pig, rabbit, and human) showed species-specific clusters of sequences, indicating that the genes duplicated after divergence of these species. Comparison of rates of synonymous and nonsynonymous nucleotide substitution suggested that gene duplication has often been followed by a period in which diversification of the mature defensins at the amino acid level has been selectively favored. In some comparisons, it appeared that amino acid differences in this region have appeared in a nonrandom fashion so as to change the pattern of residue charges. Because it has been hypothesized that the negative charge in the propiece serves to balance the positive charge in the mature defensin and thus to prevent cytotoxicity prior to cleavage, we used a maximum likelihood method of reconstructing ancestral states in order to test whether this balance has been maintained over evolutionary time in spite of rapid diversification of the mature defe...Continue Reading

Citations

Sep 23, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A L Hughes, M Yeager
Oct 29, 2008·Journal of Molecular Evolution·Lumi Viljakainen, Pekka Pamilo
Sep 1, 2005·Immunogenetics·Katja LuenserArne Ludwig
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Apr 29, 2004·Veterinary Immunology and Immunopathology·Elizabeth G DavisFrank Blecha
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Dec 15, 2000·Trends in Ecology & Evolution·Z Yang, J P Bielawski
Nov 5, 2002·Molecular Phylogenetics and Evolution·Austin L Hughes
Dec 21, 2002·Immunological Reviews·Austin L Hughes
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