title: The guardians of inherited oncogenic vulnerabilities.
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.
authors.affiliation: CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France. au.arnal@gmail.com.
authors.forename: Audrey
authors.initials: A
authors.lastname: Arnal
authors.affiliation: CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France.
authors.forename: Tazzio
authors.initials: T
authors.lastname: Tissot
authors.affiliation: Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Waurn, Ponds, Australia.
authors.forename: Beata
authors.initials: B
authors.lastname: Ujvari
authors.affiliation: Department of Biology, University of California, Riverside, California.|Center for Evolution and Cancer, University of California San Francisco, San Francisco, California.
authors.forename: Leonard
authors.initials: L
authors.lastname: Nunney
authors.affiliation: INSERM U1009, Université Paris-Sud, Gustave Roussy, Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.affiliation: INSERM U1009, Université Paris-Sud, Gustave Roussy, Villejuif, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Laplane
authors.affiliation: ISEM Institut des sciences de l'évolution, Université Montpellier 2, CNRS, Montpellier Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Bonhomme
authors.affiliation: CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France.|Centre de Recherche de la Tour du Valat, le Sambuc, 13200, Arles, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Vittecoq
authors.affiliation: University of Lille, CNRS, UMR 8198 - Evo-Eco-Paleo, 59000 Lille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Tasiemski
authors.affiliation: CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France.
authors.forename: François
authors.initials: F
authors.lastname: Renaud
authors.affiliation: Service de génétique médicale et chromosomique, Unité d'oncogénétique, CHRU de Montpellier, Hôpital Arnaud de Villeneuve, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.affiliation: CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France.|International Center for Mathematical and Computational Modeling of Complex Systems (UMI IRD/UPMC UMMISCO), 32 Avenue Henri Varagnat, 93143, Bondy Cedex, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Roche
authors.affiliation: CREEC, MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Thomas
mesh_terms: D000818:Animals; D005075:Biological Evolution; D063646:Carcinogenesis / Q000235:genetics*; D056084:Genetic Fitness; D040941:Heredity; D006801:Humans; D009154:Mutation; D012641:Selection, Genetic
keywords: Cancer; natural defenses; purifying selection; somatic mutations