Adaptive evolutionary expansion of the ribonuclease 6 in Rodentia

Abstract

Ribonuclease 6 (RNase6 or RNase K6) is a protein that belongs to a superfamily thought to be the sole vertebrate-specific enzyme known for a wide range of physiological functions, including digestion, cytotoxicity, angiogenesis, male reproduction and host defense. In our study, 51 functional genes and 11 pseudogenes were identified from 27 Rodentia species. Intriguingly, in the 3 main lineages of rodents there were multiple RNas-e6s identified in all species of Ctenohystrica, whereas only a single RNase6 was observed in other Rodentia species examined except for 2 species in the mouse-related clade. The evolutionary scenario of "birth (gene duplication) and death (gene deactivation)" and gene sorting have been demonstrated in Ctenohystrica. In addition, bursts of positive selection, diversification of isoelectric point and positive net charge have been identified in Ctenohystrica, especially at two key sites that are involved in antimicrobial function. Site Trp30 has undergone positive selection and Ile45 has changed into other residues in Group B and Group C of the Ctenohystrica. Our results demonstrated a complex and intriguing evolutionary pattern of rodent RNase6, and indicated that functional modification may have occurred, which establishes an important theoretical foundation for future functional assays in rodent RNase6.

Hypomethylation of Rnase6 Promoter Enhances Proliferation and Migration of Murine Aortic Vascular Smooth Muscle Cells and Aggravates Atherosclerosis in Mice

“…Among them, Ribonuclease 6 (Rnase6) was reported to occur in AS with up-regulated expression ( Zhao, et al, 2020 ). Rnase6 belongs to the secreted protein of the Ribonuclease A (RNaseA) superfamily and has a wide range of physiological functions, including digestion, cytotoxicity, angiogenesis, male reproduction and host defense ( Lang, et al, 2019 ). It has been reported that Rnase6 shows higher expression in uterine tissues with abnormal placental expulsion after delivery, leading to macrophage polarization toward M2 phenotype and aggravating the inflammatory process during placental expulsion ( Nelli, et al, 2019 ).…”