Roche Benjamin auteur aut IRD Sprouffske K. auteur aut IRD Hbid H. auteur aut IRD Missé Dorothée auteur aut IRD Thomas F. auteur aut IRD text journalArticle eng text/pdf born digital access If the occurrence of cancer is the result of a random lottery among cells, then body mass, a surrogate for cells number, should predict cancer incidence. Despite some support in humans, this assertion does not hold over the range of different natural animal species where cancer incidence is known. Explaining the so-called Peto's paradox' is likely to increase our understanding of how cancer defense mechanisms are shaped by natural selection. Here, we study how body mass may affect the evolutionary dynamics of tumor suppressor gene (TSG) inactivation and oncogene activation in natural animal species. We show that the rate of TSG inactivation should evolve to lower values along a gradient of body mass in a nonlinear manner, having a threshold beyond which benefits to adaptive traits cannot overcome their costs. We also show that oncogenes may be frequently activated within populations of large organisms. We then propose experimental settings that can be employed to identify protection mechanisms against cancer. We finally highlight fundamental species traits that natural selection should favor against carcinogenesis. We conclude on the necessity of comparing genomes between populations of a single species or genomes between species to better understand how evolution has molded protective mechanisms against cancer development and associated mortality. specialized biomedicine disease biology evolutionary medicine evolutionary theory 020 050 6 1 109-116 2013 1752-4571 https://www.documentation.ird.fr/hor/fdi:010058935 10.1111/eva.12025 1752-4571 [F B010058935] https://www.documentation.ird.fr/hor/fdi:010058935 https://www.documentation.ird.fr/intranet/publi/2013/02/010058935.pdf Accès réservé (Intranet de l'IRD) IRD - Base Horizon / Pleins textes 2013-03-06 2020-03-17 fdi:010058935 fre