Genomic insights into body size evolution in Carnivora support Peto's paradox

The range of body sizes in Carnivora is unparalleled in any other mammalian order-the heaviest species is 130,000 times heavier than the lightest and the longest species is 50 times longer than the shortest. However, the molecular mechanisms underlying these huge differences in body size have not been explored.

Herein, we performed a comparative genomics analysis of 20 carnivores to explore the evolutionary basis of the order's great variations in body size. Phylogenetic generalized least squares (PGLS) revealed that 337 genes were significantly related to both head body length and body mass; these genes were defined as body size associated genes (BSAGs). Fourteen positively-related BSAGs were found to be associated with obesity, and three of these were under rapid evolution in the extremely large carnivores, suggesting that these obesity-related BSAGs might have driven the body size expansion in carnivores. Interestingly, 100 BSAGs were statistically significantly enriched in cancer control in carnivores, and 15 of which were found to be under rapid evolution in extremely large carnivores. These results suggested that large carnivores might have evolved an effective mechanism to resist cancer, which could be regarded as molecular evidence to support Peto's paradox. For small carnivores, we identified 15 rapidly evolving genes and found six genes with fixed amino acid changes that were reported to reduce body size.

This study brings new insights into the molecular mechanisms that drove the diversifying evolution of body size in carnivores, and provides new target genes for exploring the mysteries of body size evolution in mammals.