Origin of GPCRs Figure 3. Scatter plot distinguishing cAMP and the Rhodopsin like sequences. The sequences which are plotted were tested with HMM search using 7tm_1 (PF00001) and Dicty_CAR (PF05462) HMM models downloaded from Pfam. The e-values for each Rhodopsin like sequence (Y-axis) is plotted against the e-values of cAMP like sequences (X-axis) in a logarithmic scale. The members are distinguished with colors corresponding to each group shown in the right corner. The dotted line in red shows the approximate cutoff which clearly distinguishes cAMP and Rhodopsin like sequences according to the HMM search with the HMM models. The special cases which are shown in green with accession id, received e-values very similar in HMM search against both the models, but were classified as Rhodopsin like sequences according to the HMM search. Those 8 sequences which belong to ciliates (2) and Fungi (6) were classified as cAMP like sequences with strong support from phylogeny, which is shown as an inset at the top. The posterior probability more than 90% is marked with a star (green). An approximate cutoff according to the phylogeny is shown as dotted lines (black). doi:10.1371/journal.pone.0029817.g003 domain architecture for the representative sequences from group I–VIII in human and for two sequences MB_7962 and MB_10341 from M. brevicollis are thoroughly described in our previous report [14]. Adhesion family members identified in S. rosetta and C. owczarzaki have long N-termini ranging from 312–4202 amino acid residues, comparative to the N-termini of the Adhesion family receptors in human, which range from 430–5906 residues. The sequences in S. rosetta and C. owczarzaki have a GPS domain characteristic for the Adhesion family members, which is not found in any other GPCR family. One exception is SALP_EGD83019.1 which lacks the GPS domain but has 4 EGF_CA domains, which are present in the sequence of EMR1 (Group II) and CELSR1 (Group III) in human. The same sequence also has one Tsp1 domain, which is found in sequence BAI1 (Group VII) and LamG domain found in sequences CELSR1 (Group III) and GPR144 (Group V). Furthermore, CASP_EFW45600.1 in C. owczarzaki has five Calx_beta domains, which are a signature for VLGR1 (the very long G protein-coupled receptors) in Metazoa. This may suggest that CASP_EFW45600.1 is a putative orthologue to VLGR1 in human. Several domains were identified that have not been reported previously in the Adhesion family like the TIG domain in the sequences SALP_EGD77907.1, SALP_EGD77908.1; the TLD domain in sequence SALP_EGD78309.1 from S. rosetta and the RLD domain in sequences CASP_EFW40287.1 and CASP_EFW39861.1 from C. owczarzaki. Interestingly, the 30 putative Adhesion family members in phylum Ascomycota of Fungi and 1 member in Alveolata have short N-termini ranging from 2– PLoS ONE | www.plosone.org 6 January 2012 | Volume 7 | Issue 1 | e29817