Comparative Genomics Reveals a Convergent Signature on the Vitamin D Receptor (VDR) in Herbivorous Mammals

Abstract Background: Dietary adaptation is one of hot topics in adaptive evolution of mammals. Herbivorous mammals generally digest structural carbohydrates (such as cellulose and hemicellulose) via intestinal microbial fermentation. However, the mechanism by which the host supports the intestinal fermentation capacity is still not well understood. To address this question, we conducted convergent amino acid scanning to identify candidate genes involving intestinal fermentation across mammalian phylogeny. Results: Among 4886 one-to-one orthologous genes, we found that 122 genes showed a significant increase of convergent signature in two foregut-fermenting families (Cercopithecidae: Rhinopithecus roxellana, Bovidae: Bos taurus and Ovis aries ) and particularly, in the vitamin D receptor (VDR), a convergent cysteine to serine substitution at amino acid 410 (VDR C410S) occurred in 14 mammalian families with intestinal fermentation capacity. As a critical role of VDR in the regulation of intestinal microbes and adaptive immunity, we employed phylogenetically independent contrast analysis to test whether the evolution of the VDR gene influenced intestinal fermentation and found this convergent amino acid substitution (VDR C410S) possess significant positively correlations with the intestinal fermentation capacity and the dietary components (plant parts except for fruits, seeds and nectar) consumed by 107 mammalian species, which indicated VDR have a positive impact on the herbivorous adaptation of intestinal fermentation. Conclusions: Our results suggest that nuclear receptor gene VDR involved in intestinal adaptive immune show rapid adaptive fixation of convergent amino acid substitutions (C410S) among herbivorous mammals with convergent methodology.