Hyper-specialized primates possess a reduced suite of xenobiotic-metabolizing cytochrome P450 genes.

Subfamilies of cytochrome P450 proteins have been strongly linked to the metabolism of physiologically disruptive compounds such as alkaloids, terpenoids, and other xenobiotics. Consistent with this function, these genes have adaptively evolved in response to environmental pressures exerted on animals, such as herbivores, that consume elevated amounts of toxic xenobiotics or plant secondary metabolites (PSMs). Theory on evolutionary tradeoffs predicts that highly specialized herbivores should exhibit a relatively narrow toolkit of adaptations to accommodate the concomitantly narrow arrays of PSMs in their diets. The bamboo lemurs of Madagascar (genera Prolemur and Hapalemur) represent an interesting test case for this theory because of their dietary hyper-specialization, as these lemurs consume bamboo and grasses at rates otherwise unseen in the order Primates. To test whether the hyper-specialized folivory of these primates is reflected in a similarly specialized and narrow P450 gene suite, we assembled a dataset of confidently assembled CYP1-3 genes for two species of bamboo lemur as well as additional lemur species. We tested the predictions that bamboo lemurs would exhibit, first, greater rates of gene loss for xenobiotic-metabolizing P450s and, second, relaxed selection on xenobiotic-metabolizing P450 subfamilies relative to lemurs without such dietary hyper-specialization. We found support for the first prediction, related to gene loss, in the CYP2B, CYP2C, CYP2D, CYP2J, and CYP3A subfamilies, all of which encode xenobiotic metabolizers. We additionally inferred relaxation of selection for the CYP2F and CYP2J subfamilies. The evolution of the P450 genes in bamboo lemurs provides support for the evolutionary tradeoff hypothesis, and we further hypothesize that, rather than adapting to a general array of PSMs, bamboo lemurs have instead adapted to the primary toxin in their diet, the highly potent poison cyanide. HighlightsO_LISome of the most specialized diets among primates are those of bamboo lemurs. C_LIO_LIBamboo lemurs have fewer xenobiotic-metabolizing P450 genes than other lemurs. C_LIO_LINatural selection has relaxed on the CYP2F and CYP2J subfamilies in bamboo lemurs. C_LI