Peto's paradox revisited: theoretical evolutionary dynamics of cancer in wild populations

Evolutionary Applications

Benjamin Roche¹  Kathleen Sprouffske³  Hassan Hbid²  Dorothée Missé¹ 

[1] CREEC, Université Montpellier 2, Montpellier, France;IRD, UMMISCO (UMI IRD/UPMC), Bondy, France;Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland

关键词: biomedicine;    disease biology;    evolutionary medicine;    evolutionary theory;   

DOI  :  10.1111/eva.12025

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
© 2012 The Authors. Evolutionary Applications published by Blackwell Publishing Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.