Convergent relaxation of molecular constraint in mammalian herbivores highlights the roles of liver and kidney functions in carnivory

Mammalia comprises a great diversity of diet types and associated adaptations. An understanding of the genomic mechanisms underlying these adaptations may offer insights for improving human health. Comparative genomic studies of diet that employ taxonomically restricted analyses or simplified diet classifications may suffer reduced power to detect molecular convergence associated with diet evolution. Here, we used a quantitative carnivory score--indicative of the amount of animal protein in the diet--for 80 mammalian species to detect significant correlations between the relative evolutionary rates of genes and changes in diet. We identified six genes--ACADSB, CLDN16, CPB1, PNLIP, SLC13A2, and SLC14A2--that experienced significant changes in evolutionary constraint alongside changes in carnivory score, becoming less constrained in lineages evolving more herbivorous diets. We further considered the biological functions associated with diet evolution and observed that pathways related to amino acid and lipid metabolism, biological oxidation, and small molecule transport experienced reduced purifying selection as lineages became more herbivorous. Liver and kidney functions showed similar patterns of constraint with dietary change. Our results indicate that, in highly carnivorous lineages, selection acts on the liver and kidneys to maintain sufficient metabolism and excretion of substances found in excess in carnivorous diets. These biological functions become less important with the evolution of increasing herbivory, so experience a relaxation of constraint in more herbivorous lineages.