Origin and Functional Diversification of an Amphibian Defense Peptide Arsenal
Open Access
- 1 August 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Genetics
- Vol. 9 (8), e1003662
- https://doi.org/10.1371/journal.pgen.1003662
Abstract
The skin secretion of many amphibians contains an arsenal of bioactive molecules, including hormone-like peptides (HLPs) acting as defense toxins against predators, and antimicrobial peptides (AMPs) providing protection against infectious microorganisms. Several amphibian taxa seem to have independently acquired the genes to produce skin-secreted peptide arsenals, but it remains unknown how these originated from a non-defensive ancestral gene and evolved diverse defense functions against predators and pathogens. We conducted transcriptome, genome, peptidome and phylogenetic analyses to chart the full gene repertoire underlying the defense peptide arsenal of the frog Silurana tropicalis and reconstruct its evolutionary history. Our study uncovers a cluster of 13 transcriptionally active genes, together encoding up to 19 peptides, including diverse HLP homologues and AMPs. This gene cluster arose from a duplicated gastrointestinal hormone gene that attained a HLP-like defense function after major remodeling of its promoter region. Instead, new defense functions, including antimicrobial activity, arose by mutation of the precursor proteins, resulting in the proteolytic processing of secondary peptides alongside the original ones. Although gene duplication did not trigger functional innovation, it may have subsequently facilitated the convergent loss of the original function in multiple gene lineages (subfunctionalization), completing their transformation from HLP gene to AMP gene. The processing of multiple peptides from a single precursor entails a mechanism through which peptide-encoding genes may establish new functions without the need for gene duplication to avoid adaptive conflicts with older ones. Many amphibians defend themselves against predation and infections by secreting a mixture of gene-encoded toxins and antimicrobials. How does such an integrated defense weapon arise and how does it diversify to gain distinct antipredatory and antimicrobial functions? We took advantage of the availability of a sequenced genome for the African clawed frog Silurana tropicalis to provide the first comprehensive overview of an amphibian peptide defense arsenal, from its underlying genes to its bioactive components. A reconstruction of the evolutionary history of this gene repertoire allows us to elucidate the timing and mode of evolution of distinct defense functions. Our study shows that the basal transition from a gastrointestinal hormone function to a skin-secretory defense function was accompanied by major restructuring of regulatory sequences in the ancestral gene. Instead, subsequently diversifying defense genes underwent functional shifts by entering a bifunctional stage (by cleavage of two distinct defense peptides from a single precursor protein) and occasionally losing the original defense function (by loss of the original defense peptide). This pattern provides an evolutionary explanation for the processing of structurally or functionally unrelated toxins from the same or closely related precursor proteins in other poisonous and venomous animals.Keywords
This publication has 100 references indexed in Scilit:
- Escape from Adaptive Conflict follows from weak functional trade-offs and mutational robustnessProceedings of the National Academy of Sciences of the United States of America, 2012
- Extensive and Continuous Duplication Facilitates Rapid Evolution and Diversification of Gene FamiliesMolecular Biology and Evolution, 2012
- Venom evolution through gene duplicationsGene, 2012
- MEME SUITE: tools for motif discovery and searchingNucleic Acids Research, 2009
- Ohno's dilemma: Evolution of new genes under continuous selectionProceedings of the National Academy of Sciences of the United States of America, 2007
- PAML 4: Phylogenetic Analysis by Maximum LikelihoodMolecular Biology and Evolution, 2007
- Global patterns of diversification in the history of modern amphibiansProceedings of the National Academy of Sciences of the United States of America, 2007
- Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?Nature Reviews Microbiology, 2005
- MAFFT version 5: improvement in accuracy of multiple sequence alignmentNucleic Acids Research, 2005
- Antimicrobial peptides of multicellular organismsNature, 2002