期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：1
页码：88-93
DOI：10.1073/pnas.1419399112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceIt was previously believed that placental mammals present no variability in oxytocin (OXT). The present study reports novel data on the diversity of OXT and its receptor (OXTR) in primate species, including New World monkeys. Contrary to prior expectations, we found three novel OXT forms and several OXTR nonsynonymous changes not previously described. In the Cebidae family, signals of positive selection were found for an OXT variant at position 8, which is associated with larger litter sizes. We detected positive selection for OXTR forms and report a coevolutionary process between changes in OXT and OXTR. Oxytocin is a nonapeptide involved in a wide range of physiologic and behavioral functions. Until recently, it was believed that an unmodified oxytocin sequence was present in all placental mammals. This study analyzed oxytocin (OXT) in 29 primate species and the oxytocin receptor (OXTR) in 21 of these species. We report here three novel OXT forms in the New World monkeys, as well as a more extensive distribution of a previously described variant (Leu8Pro). In structural terms, these OXTs share the same three low-energy conformations in solution during molecular dynamic simulations, with subtle differences in their side chains. A consistent signal of positive selection was detected in the Cebidae family, and OXT position 8 showed a statistically significant (P = 0.013) correlation with litter size. Several OXTR changes were identified, some of them promoting gain or loss of putative phosphorylation sites, with possible consequences for receptor internalization and desensitization. OXTR amino acid sites are under positive selection, and intramolecular and intermolecular coevolutionary processes with OXT were also detected. We suggest that some New World monkey OXT-OXTR forms can be correlated to male parental care through the increase of cross-reactivity with its correlated vasopressin system.
