Evolutionary relationships of Latrophilins with other Adhesion GPCR groups. The evolutionary history of C. elegans (ce, light green box) and Drosophila melanogaster (dm, light yellow box) Latrophilin-like (LAT, Cirl, LEC) and Flamingo-like (FMI) receptors in relation to human, mouse, chicken, and zebrafish Adhesion GPCRs was constructed using the amino acid sequence of the 7TM region. For comparison purposes, Latrophilin-like sequences from other invertebrates were included. Muscarinic acetyl choline receptors of the respective species were used as outgroup. All sequence data are retrieved from NCBI. The evolutionary history was inferred using the Neighbor-Joining method (Saitou and Nei, 1987). The optimal tree with the sum of branch length = 38.4 is shown. The evolutionary distances were computed using the Poisson correction method (Zuckerkandl and Pauling, 1965) and are shown as units of the number of amino acid substitutions per site. The analysis involved 180 amino acid sequences. All positions with less than 95% site coverage were eliminated. That is, fewer than 5% alignment gaps, missing data, and ambiguous bases were allowed at any position. There were a total of 202 positions in the final dataset. Evolutionary analyses were conducted in MEGA7 (Kumar et al., 2016). The left, less complex tree shows only the topology of the groups. The respective right tree displays the calculated branch lengths but the receptor groups are condensed into proportional triangles except of ADGRL, ADGRE and the muscarinic acetylcholine receptors (mAChR). The branch point of ADGRL and ADGRE is marked with a red circle. The mAChR branch is marked with a blue circle. Species are: hs, Homo sapiens (Mammalia); mm, Mus musculus (Mammalia); gg, Gallus gallus (Avea); dr, Danio rerio (Osteichthyes); sk, Saccoglossus kowalevskii (Hemichordata); ci, Ciona intestinalis (Tunicata); ac, Acanthaster planc (Echinodermata); sp, Strongylocentrotus purpuratus (Echinodermata); my, Mizuhopecten yessoensis (Mollusca); cg, Crassostrea gigas (Mollusca); ob, Octopus bimaculoides (Mollusca); dm, Drosophila melanogaster (Insecta); la, Lingula anatina (Brachiopoda); ct, Capitella teleta (Annelida); ce, Caenorhabditis elegans (Nematoda); hd, Hypsibius dujardini (Tardigrada); rv, Ramazzottius varieornatus (Tardigrada); of, Orbicella faveolata (Cnidaria); pd, Pocillopora damicornis (Cnidaria); aq, Amphimedon queenslandica (Parazoa).