PUBLICATION
Evolution of the relaxin-like peptide family
- Authors
- Wilkinson, T.N., Speed, T.P., Tregear, G.W., and Bathgate, R.A.
- ID
- ZDB-PUB-050215-2
- Date
- 2005
- Source
- BMC Evolutionary Biology 5(1): 14 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Dogs
- Evolution, Molecular*
- Humans
- Insulin/classification*
- Insulin/genetics
- Mice
- Molecular Sequence Data
- Phylogeny*
- Rats
- Relaxin/classification*
- Relaxin/genetics*
- Sequence Alignment
- Sequence Analysis, Protein
- PubMed
- 15707501 Full text @ BMC Evol. Biol.
Citation
Wilkinson, T.N., Speed, T.P., Tregear, G.W., and Bathgate, R.A. (2005) Evolution of the relaxin-like peptide family. BMC Evolutionary Biology. 5(1):14.
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 (dN/dS) 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping