Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets

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 use 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 have identified six genes-<i>ACADSB</i>, <i>CLDN16</i>, <i>CPB1</i>, <i>PNLIP</i>, <i>SLC13A2</i>, and <i>SLC14A2</i>-that experienced significant changes in evolutionary constraint alongside changes in carnivory score, becoming less constrained in lineages evolving more herbivorous diets. We further consider the biological functions associated with diet evolution and observe 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 show similar patterns of constraint with dietary change. Our results indicate that these functions are important for the consumption of animal matter and become less important with the evolution of increasing herbivory. So, genes expressed in these tissues experience a relaxation of evolutionary constraint in more herbivorous lineages.