5-HT receptor candidate selection.

5-HT profile HMM hits are ranked by E-value for S. mediterranea. Additional sequences were appended via homology searches. This putative list of planarian 5-HT receptors was searched against the NCBI nr database using BLASTp. Receptors that exclusively showed serotonin-related homology in their top returned hits are marked with ‘+’. HMMTOP [50] was used to predict the number of TM domains for each sequence. Putative 5-HT receptors from S. mansoni[23] and D. japonica[51] were searched against the filtered HMM pool. The two nearest-related homologs for each of four S. mansoni receptors are shown, along with E-value and overlap length for each pairing. Similarly, the top pairings for each of three D. japonica receptors are shown. Three sequence clusters (bold) show high sequence conservation between parasite and planarian sequences. DjSER-7 has been previously deorphanized [30] and we therefore excluded this cluster from further consideration. Among the two remaining options, our choice of the highlighted sequence cluster is justified as follows: 1) the planarian sequences in this grouping share the highest level of sequence identity with their parasite sequelog, 2) the presence of two closely-related planarian sequences improves the likelihood of success for degenerate PCR as a strategy to amplify the D. tigrina homolog, and 3) deorphanization of a receptor in this cluster will assign a pharmacological identity to a novel subset of GPCRs.