MBE Advance Access published online on March 5, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg060
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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1 MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU Scotland
* To whom correspondence should be addressed. E-mail: julia{at}hgu.mrc.ac.uk.
Key Words:
adaptive evolution, beta-defensin, positive selection, mus Musculus
© 2003 Society for Molecular Biology and Evolution
Original Articles
Signal Sequence Conservation and Mature Peptide Divergence within Subgroups of the Murine
-Defensin Gene Family
Abstract 
-defensins are two exon genes which encode broad spectrum antimicrobial cationic peptides. We have analysed the largest murine cluster of these genes which localises to chromosome 8. Using hidden Markov models, we identified six -defensin exon 2-like sequences and subsequently found full-length expressed transcripts for these novel genes. Expression was high in brain and reproductive tissues. Eleven -defensins could be grouped into two clear subgroups by virtue of their position and high signal sequence (exon 1 encoded) identity. In contrast however, there was a very low level of sequence conservation in the exon 2 region encoding the mature antimicrobial peptide. Examination of the gene sequences of orthologues in other rodents also revealed an excess of nucleotide changes that altered amino acids in the mature peptide region. Evolutionary analysis revealed strong evidence that following gene duplication, exon 1 and surrounding non-coding DNA show little divergence within subgroups. The focus for rapid sequence divergence is localised in the DNA encoding the mature peptide and this is driven by accelerated positive selection. This mechanism of evolution is consistent with the role of this gene family as defence against bacterial pathogens and the sequence changes have implications for novel antibiotic design.
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