The guardians of inherited oncogenic vulnerabilities

Audrey Arnal; Tazzio Tissot; Beata Ujvari; Leonard Nunney; Eric Solary; Lucie Laplane; François Bonhomme; Marion Vittecoq; Aurélie Tasiemski; François Renaud; Pascal Pujol; Benjamin Roche; Frédéric Thomas

doi:10.1111/evo.12809

The guardians of inherited oncogenic vulnerabilities

Audrey Arnal, Tazzio Tissot, Beata Ujvari, Leonard Nunney, Eric Solary, Lucie Laplane, François Bonhomme, Marion Vittecoq, Aurélie Tasiemski, François Renaud, Pascal Pujol, Benjamin Roche, Frédéric Thomas

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1-6
Number of pages	6
Journal	Evolution
Volume	70
Issue number	1
DOIs	https://doi.org/10.1111/evo.12809
Publication status	Published - 1 Jan 2016
Externally published	Yes

Keywords

Cancer
Natural defenses
Purifying selection
Somatic mutations

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10.1111/evo.12809

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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.",

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AU - Arnal, Audrey

AU - Tissot, Tazzio

AU - Ujvari, Beata

AU - Nunney, Leonard

AU - Solary, Eric

AU - Laplane, Lucie

AU - Bonhomme, François

AU - Vittecoq, Marion

AU - Tasiemski, Aurélie

AU - Renaud, François

AU - Pujol, Pascal

AU - Roche, Benjamin

AU - Thomas, Frédéric

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Cancer

KW - Natural defenses

KW - Purifying selection

KW - Somatic mutations

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The guardians of inherited oncogenic vulnerabilities

Abstract

Keywords

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