Fig. 1.

Phylogenomics pipeline for the study of PS evolution. A standard phylogenomics strategy was used to derive sets of potential peptide GPCRs (receptor search, A) for all of the species considered (Methods). The final three phylogenetic trees of bilaterian rhodopsin GPCRs (β and γ rGPCRs and sGPCRs) were used to derive potential ancestral PSs. Then, to isolate potential peptide precursor sequences (peptide search, B) a noncanonical strategy was used, which involved the use of an HMM designed to find candidate peptide precursors in each of the bilaterian species and the construction of peptide phylogenetic trees using the neighbor-joining method and a normalized kernel-based distance (Methods).