Background The range of body sizes in Carnivora is unparalleled in any other mammalian order, with more than 130,000 times in body mass and 50 times in length. However, the molecular mechanisms underlying the huge difference in body size of Carnivora have not been explored so far. Results Herein, we performed a comparative genomics analysis of 20 carnivores to explore the genetic basis of great body size variation in carnivores. Phylogenetic generalized least squares (PGLS) revealed that 337

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... es 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 which were identified to be under rapid evolution in the extremely large body-sized carnivores, which suggested that these obesity-related BSAGs might have driven the body size expansion in carnivores. Interestingly, 100 BSAGs were examined to be associated with cancer control in carnivores, particularly 15 cancer-related genes were found to be under rapid evolution in extremely large carnivores. These results strongly suggested that large body-sized carnivores might have evolved effective mechanism to resist cancer, which could be regarded as molecular evidence to support for the 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. Conclusion 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.