Molecular evolution of animal antimicrobial peptides: widespread moderate positive selection

An increasing number of studies in both vertebrates and invertebrates show that the evolution of antimicrobial peptides is driven by positive selection. Because these diverse molecules show potential for therapeutic applications, they are currently the targets of much structural and functional research, providing extensive background data for evolutionary studies. In this paper, patterns of molecular evolution in antimicrobial peptide genes are reviewed. Evidence for positive selection on antimicrobial peptides includes an excess of nonsynonymous nucleotide substitutions, an excess of charge-changing amino acid substitutions, nonneutral patterns of allelic variation, and functional assays in vivo and in vitro that show improved antimicrobial effects for derived sequence variants. Positive selection on antimicrobial peptides may be as common as, but perhaps weaker than, selection on the best-known example of adaptively evolving immunity genes, the major histocompatibility complex. Thus, antimicrobial peptides present a useful and underutilized model for the study of adaptive molecular evolution.