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The guardians of inherited oncogenic vulnerabilities |
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| Authors: | Audrey Arnal Beata Ujvari Leonard Nunney Eric Solary Lucie Laplane François Bonhomme Marion Vittecoq Aurélie Tasiemski François Renaud Pascal Pujol Benjamin Roche Frédéric Thomas |
| Affiliation: | 1. CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, FranceBoth authors contributed equally to this work.;2. Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Waurn, Ponds, Australia;3. Department of Biology, University of California, Riverside, California;4. Center for Evolution and Cancer, University of California San Francisco, San Francisco, California;5. INSERM U1009, Université Paris‐Sud, Gustave Roussy, Villejuif, France;6. ISEM Institut des sciences de l’évolution, Université Montpellier 2, CNRS, Montpellier Cedex, France;7. CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, France;8. Centre de Recherche de la Tour du Valat, le Sambuc, Arles, France;9. University of Lille, CNRS, UMR 8198 ‐ Evo‐Eco‐Paleo, 59000 Lille, France;10. Service de génétique médicale et chromosomique, Unité d'oncogénétique, CHRU de Montpellier, H?pital Arnaud de Villeneuve, Montpellier, France;11. International Center for Mathematical and Computational Modeling of Complex Systems (UMI IRD/UPMC UMMISCO), 32 Avenue Henri Varagnat, Bondy Cedex, France |
| Abstract: | Similar to seemingly maladaptive genes in general, the persistence of inherited cancer‐causing mutant alleles in populations remains a challenging question for evolutionary biologists. In addition to traditional explanations such as senescence or antagonistic pleiotropy, here we put forward a new hypothesis to explain the retention of oncogenic mutations. We propose that although natural defenses evolve to prevent neoplasm formation and progression thus increasing organismal fitness, they also conceal the effects of cancer‐causing mutant alleles on fitness and concomitantly protect inherited ones from purging by purifying selection. We also argue for the importance of the ecological contexts experienced by individuals and/or species. These contexts determine the locally predominant fitness‐reducing risks, and hence can aid the prediction of how natural selection will influence cancer outcomes. |
| Keywords: | Cancer natural defenses purifying selection somatic mutations |