BackgroundMammalia 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 and 80 mammalian species to detect significant correlations between the relative evolutionary rates of genes and changes in diet. Increases in this carnivory score indicated increasing amounts of animal protein in a species’ diet.ResultsWe identified six genes—ACADSB,CLDN16,CPB1,PNLIP,SLC13A2, andSLC14A2—that experienced significant evolutionary constraint and greater functional importance as increasingly carnivorous diets evolved. 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 were evolutionarily constrained in association with increased carnivory. Liver and kidney functions showed a similar pattern of greater constraint as carnivory increases.ConclusionsOur results indicate that, during adaptation to increasing carnivory, selection acts on the liver and kidneys to maintain sufficient metabolism and excretion of substances found in excess in carnivorous diets.