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

Abstract

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 and 13 additional lemur species. With this dataset, 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 prediction of gene loss in the CYP2B, CYP2C, CYP2D, CYP2J, and CYP3A subfamilies, all of which encode xenobiotic metabolizers. We inferred relaxation of selection for the CYP1A and CYP2D subfamilies. The CYP2F subfamily exhibited a signal of significant intensification of selection in the bamboo-lemur lineage. 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.