Evolution of the sarafotoxin/endothelin superfamily of proteins

Sixteen protein and nucleic acid sequences from the vasoconstrictor sarafotoxin/endothelin/endothelin-like superfamily of peptides were studied, and the evolutionary relationships between the sarafotoxin and endothelin gene families as well as the phylogenetic topology within each gene family and the three endothelin subfamilies was reconstructed. The endothelin gene family has diverged from an ancestral gene that has experienced an exon duplication event followed by two gene duplication events. The sarafotoxins' lineage diverged from the ancestral gene prior to the first endothelin gene duplication event. Analysis of the resulting phylogenetic trees revealed that in several lineages, the peptides have independently accumulated identical replacements in position 2, therefore supporting the hypothesis that residue 2 is crucial to their activity.