Molecular strategies in biological evolution of antimicrobial peptides.

Pierre Nicolas, Damien Vanhoye, Mohamed Amiche
Author Information
  1. Pierre Nicolas: Laboratoire de Bioactivation des Peptides, Institut Jacques Monod, 2 Place Jussieu, 75251 Paris Cedex 05, France. pnicolas@ddr.jussieu.fr

Abstract

Gene-encoded antimicrobial peptides that protect the skin of hylid and ranin frogs against noxious microorganisms are processed from a unique family of precursor polypeptides with a unique pattern of conserved and variable regions opposite to that of conventional secreted peptides. Precursors belonging to this family, designated the preprodermaseptin, have a common N-terminal preproregion that is remarkably well conserved both within and between species, but a hypervariable C-terminal domain corresponding to antimicrobial peptides with very different lengths, sequences, charges and antimicrobial spectra. Each frog species has its own distinct panoply of 10-20 antimicrobial peptides so that the 5000 species of ranids and hylids may produce approximately 100,000 different peptide antibiotics. The strategy that these frogs have evolved to generate this enormous array of peptides includes repeated duplications of a 150 million years old ancestral gene, focal hypermutation of the antimicrobial peptide domain maybe involving a mutagenic DNA polymerase similar to Escherichia coli Pol V, and subsequent actions of positive (diversifying) selection. The hyperdivergence of skin antimicrobial peptides can be viewed as the successful evolution of a multi-drug defense system that provides frogs with maximum protection against rapidly changing microbial biota and minimizes the chance of microorganisms developing resistance to individual peptides. The impressive variations in the expression of frog skin antimicrobial peptides may be exploited for discovering new molecules and structural motifs targeting specific microorganisms for which the therapeutic armamentarium is scarce.

MeSH Term

Amino Acid Sequence
Animals
Antimicrobial Cationic Peptides
Base Sequence
Evolution, Molecular
Molecular Sequence Data
Mutagenesis
Phylogeny
Protein Sorting Signals
Protein Structure, Tertiary

Chemicals

Antimicrobial Cationic Peptides
Protein Sorting Signals

Word Cloud

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