Evolution of the relaxin-like peptide family

Wilkinson, TN; Speed, TP; Tregear, GW; Bathgate, RA

Author(s): Wilkinson, TN; Speed, TP; Tregear, GW; Bathgate, RA;
Journal Title: BMC EVOLUTIONARY BIOLOGY
Publication Type: Journal Article
Abstract: Background: The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1, 2 and 3, and the insulin-like (INSL) peptides, INSL3, INSL4, INSL5 and INSL6. The functions of relaxin-3, INSL4, INSL5, INSL6 remain uncharacterised. The evolution of this family has been contentious; high sequence variability is seen between closely related species, while distantly related species show high similarity; an invertebrate relaxin sequence has been reported, while a relaxin gene has not been found in the avian and ruminant lineages. Results: Sequence similarity searches of genomic and EST data identified homologs of relaxin-like peptides in mammals, and non-mammalian vertebrates such as fish. Phylogenetic analysis was used to resolve the evolution of the family. Searches were unable to identify an invertebrate relaxin-like peptide. The published relaxin cDNA sequence in the tunicate, Ciona intestinalis was not present in the completed C. intestinalis genome. The newly discovered relaxin-3 is likely to be the ancestral relaxin. Multiple relaxin-3-like sequences are present in fugu fish (Takifugu rubripes) and zebrafish (Danio rerio), but these appear to be specific to the fish lineage. Possible relaxin-1 and INSL5 homologs were also identified in fish and frog species, placing their emergence prior to mammalia, earlier than previously believed. Furthermore, estimates of synonymous and nonsynonymous substitution rates (d(N)/d(S)) suggest that the emergence of relaxin-1, INSL4 and INSL6 during mammalia was driven by positive Darwinian selection, hence these peptides are likely to have novel and in the case of relaxin-1, which is still under positive selection in humans and the great apes, possibly still evolving functions. In contrast, relaxin-3 is constrained by strong purifying selection, demonstrating it must have a highly conserved function, supporting its hypothesized important neuropeptide role. Conclusions: We present a phylogeny describing the evolutionary history of the relaxin-like peptide family and show that positive selection has driven the evolution of the most recent members of the family.
Publisher: BIOMED CENTRAL LTD
Keywords: CAMEL CAMELUS-DROMEDARIUS; POSITIVE SELECTION; PHYLOGENETIC ANALYSIS; MAXIMUM-LIKELIHOOD; RAPID EVOLUTION; GENE; RECEPTOR; INSULIN; IDENTIFICATION; HORMONE
Publisher's Version: https://doi.org/10.1186/1471-2148-5-14
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Creation Date: 2005-02-12 12:00:00