Coordinated Amino Acid Changes in the Evolution of Mammalian Defensins |
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Authors: | Austin L Hughes Meredith Yeager |
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Institution: | (1) Department of Biology, 208 Mueller Laboratory, The Pennsylvania State University, University Park, PA 16802, USA, US;(2) Institute of Molecular Evolutionary Genetics, The Pennsylvania State University, University Park, PA 16802, USA, US |
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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 defensin at the amino
acid level. Reconstructed ancestral sequences always maintained a charge balance between mature defensin and propiece, and
changes in the net positive charge of the mature defensin were balanced by corresponding changes in the propiece. The results
support the hypothesis that, in the evolution of these proteins, amino acid changes have occurred in a coordinated fashion
so as to preserve an adaptive phenotype.
Received: 23 October 1996 / Accepted: 7 January 1997 |
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Keywords: | : Mammalian defensin — Amino acid — Propiece |
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