Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores

Abstract

The repeated evolution of dietary specialization represents a hallmark of mammalian ecology. To detect genomic changes that are associated with dietary adaptations, we performed a systematic screen for convergent gene losses associated with an obligate herbivorous or carnivorous diet in 31 placental mammals. For herbivores, our screen discovered the repeated loss of the triglyceride lipase inhibitor PNLIPRP1, suggesting enhanced triglyceride digestion efficiency. Furthermore, several herbivores lost the pancreatic exocytosis factor SYCN, providing an explanation for continuous pancreatic zymogen secretion in these species. For carnivores, we discovered the repeated loss of the hormone-receptor pair INSL5-RXFP4 that regulates appetite and glucose homeostasis, which likely relates to irregular feeding patterns and constant gluconeogenesis. Furthermore, reflecting the reduced need to metabolize plant-derived xenobiotics, several carnivores lost the xenobiotic receptors NR1I3 and NR1I2 Finally, the carnivore-associated loss of the gastrointestinal host defense gene NOX1 could be related to a reduced gut microbiome diversity. By revealing convergent gene losses associated with differences in dietary composition, feeding patterns, and gut microbiomes, our study contributes to understanding how similar dietary specializations evolved repeatedly in mammals.

Keywords: carnivorous diet; convergent gene loss; herbivorous diet; metabolism; physiology.

Fig. 1.

Overview of convergent gene losses in herbivorous or carnivorous mammals. A strict herbivorous or carnivorous diet evolved several times independently in mammals. The six herbivore and five carnivore lineages are indicated by red and blue backgrounds, respectively. Species in bold font were included in the initial genome-wide screen; species in dark gray font were manually inspected for the presence of shared gene-inactivating mutations. The loss patterns of diet-related genes that are preferentially lost in either herbivores or carnivores are shown by red crosses. Gene losses that already occurred in the ancestor of related species, inferred from shared inactivating mutations, are indicated by red boxes. Animal silhouettes were downloaded from phylopic.org/ and are a courtesy of Steven Traver, David Orr, Oscar Sanisidro, Yan Wong, and Michael Keesey.

Fig. 2.

Examples of inactivating mutations in genes that are preferentially lost in herbivores (A and B) or carnivores (C–F). The coding exon–intron structure of each diet-related gene is shown at the top. For space considerations, Insets show only one representative inactivating mutation for only one gene-loss lineage, distinguishing herbivores by blue font and carnivores by red font. Black and gray boxes indicate nucleotides that belong to the same codon. All inactivating mutations in these genes are validated by raw DNA sequencing reads and are shown in SI Appendix, Figs. S3–S8.

Fig. 3.

Maximum percentage of the intact reading frame (%intact) of genes that were preferentially lost in herbivores (A and B) and carnivores (C–F). (C) While RXFP4 is truly lost in the herbivorous pika, several other herbivores exhibit a %intact < 100% due to inactivating mutations that shorten the C terminus of the protein, but do not affect the last transmembrane domain (SI Appendix, Fig. S23). Variable C termini are relatively common in conserved genes (56) and therefore do not indicate gene loss.