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.
journal_name
Evol Appljournal_title
Evolutionary applicationsauthors
Roche B,Sprouffske K,Hbid H,Missé D,Thomas Fdoi
10.1111/eva.12025subject
Has Abstractpub_date
2013-01-01 00:00:00pages
109-16issue
1issn
1752-4571journal_volume
6pub_type
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