tailieunhanh - Báo cáo khoa học: Antimicrobial peptides from hylid and ranin frogs originated from a 150-million-year-old ancestral precursor with a conserved signal peptide but a hypermutable antimicrobial domain

The dermal glands of frogs produce antimicrobial peptides that protect the skin against noxious microorganisms and assist in wound repair. The sequences of these peptides are very dissimilar, both within and between species, so that the 5000 living anuran frogs may produce 100 000 different antimicrobial peptides. The antimicrobial peptides of South American hylid frogs are derived from precursors, the preprodermaseptins, whose signal peptides and intervening sequences are remarkably conserved, but their C-terminal domains are markedly diverse, resulting in mature peptides with different lengths, sequences and antimicrobial spectra | Eur. J. Biochem. 270 2068-2081 2003 FEBS 2003 doi j Antimicrobial peptides from hylid and ranin frogs originated from a 150-million-year-old ancestral precursor with a conserved signal peptide but a hypermutable antimicrobial domain Damien Vanhoye Francine Bruston Pierre Nicolas and Mohamed Amiche Laboratoire de Bioactivation des Peptides Institut Jacques Monod Paris France The dermal glands of frogs produce antimicrobial peptides that protect the skin against noxious microorganisms and assist in wound repair. The sequences of these peptides are very dissimilar both within and between species so that the 5000 living anuran frogs may produce w 100 000 different antimicrobial peptides. The antimicrobial peptides of South American hylid frogs are derived from precursors the preprodermaseptins whose signal peptides and intervening sequences are remarkably conserved but their C-terminal domains are markedly diverse resulting in mature peptides with different lengths sequences and antimicrobial spectra. We have used the extreme conservation in the preproregion of preprodermaseptin transcripts to identify new members of this family in Australian and South American hylids. All these peptides are cationic amphipathic and a-helical. They killed a broad spectrum of microorganisms and acted in synergy. 42 preprodermaseptin gene sequences from 10 species of hylid and ranin frogs were analyzed in the context of their phylogeny and biogeography and of geophysical models for the fragmentation of Gondwana to examine the strategy that these frogs have evolved to generate an enormous array of peptide antibiotics. The hyperdivergence of modern antimicrobial peptides and the number of peptides per species result from repeated duplications of a w 150-million-year-old ancestral gene and accelerated mutations of the mature peptide domain probably involving a mutagenic error-prone DNA polymerase similar to Escherichia coli Pol V. The presence of antimicrobial