Uneven evolutionary rate of the melatonin-related receptor gene (GPR50) in primates

The melatonin-related receptor GPR50 plays an important role in mammalian adaptive thermogenesis in response to calorie intake. The evolutionary history of the GPR50 gene is poorly understood in primates; however, it has been reported that GPR50 is the mammalian ortholog of Mel1c, which has been well characterized. In this study, the complete coding sequences of the GPR50 gene in the Sichuan snub-nosed monkeys (Rhinopithecus roxellana) and Tibetan macaques (Macaca thibetana) were sequenced, and the orthologous nucleotide acid sequences of the GPR50 gene in 11 other primate species were downloaded from GenBank. Thirteen species representing 6 major primate lineages (human, great ape, lesser ape, Old World monkey, New World monkey, and prosimian monkey) were subjected to statistical analyses. A selective test showed that the entire GPR50 gene sequence is under strong purifying selection in these primates but has a significantly different evolutionary rate among the 6 major primate lineages. Notably, both the Homo and Pan branches exhibited an ω ratio >1, indicating accelerated evolution of the two lineages. Further analysis of different domains revealed that the acceleration trend was more significant in the C-terminal domain (CTD). Interestingly, in the alignment of 13 primate GPR50 nucleotide acid sequences, numerous insertions or deletions were only found in the CTD region, implying that this region may play a key role in the process of primate GPR50 evolution. The results provide deeper insight into the functional evolution of GPR50 in mammals at the molecular level.