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DIET'S ROLE IN SHAPING MAMMALIAN GENOMIC EVOLUTION

BACKGROUND

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.

OUR STUDY

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.

We identified six genes—ACADSB, CLDN16, CPB1, PNLIP, SLC13A2, and SLC14A2—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.

rerconverge_results_v2.png

Top genes and pathways with signatures of diet-associated evolutionary constraint. (a) Genes identified by RERconverge as having a significant association between relative evolutionary rate and change in carnivory score. A negative correlation (Rho) indicates that the gene evolves slower, and may be of greater functional importance, the larger the increase in carnivory score. A positive correlation indicates slower evolution with larger decreases in carnivory score. After 100,000 permulations, six genes showed a significant association, and each evolved slower in association with increased carnivory (FDR=0.05). (b) Tissues associated with positive and negative correlations, where: 1 = liver, 2 = kidneys, 3 = tibial artery, 4 = pancreas, 5 = small intestine. Some tissues are annotated with the genes found to be individually significant. The annotated tissues are the locations of highest expression for those genes in adult humans, according to the Genotype-Tissue Expression Project. The gene sets of red organs were more evolutionarily constrained in lineages with increasing carnivory. Blue indicates more evolutionary constraint in lineages with decreasing carnivory. Gray represents organs that were not significantly enriched but were sites of strongest expression for slowly evolving genes. (c) Biological functions showing constraint associated with change in diet. We used RERconverge to test for enrichment of gene sets representing tissues (n=50), gene pathways (n=1,290), and abnormal phenotypes (n=3,560). For tissues, two gene sets were enriched for negative correlations and one set was enriched for positive correlations. For gene pathways, 26 gene sets were enriched for negative correlations and 8 sets were enriched for positive correlations. For abnormal phenotypes, four gene sets were enriched for negative correlations.

Our 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.

FUTURE WORK

Phenotype evolution is primarily driven by changes in cis-regulatory elements. Future work will identify non-coding genomic regions that are associated with the evolution of increasingly carnivorous diets across Mammalia.

MD Pollard, WK Meyer, EE Puckett. 2024. Convergent relaxation of molecular constraint in herbivores reveals the changing role of liver and kidney functions across mammalian diets. Genome Research 34: . https://doi.org/10.1101/gr.278930.124

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