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Trade-off between reducing mutational accumulation and increasing commitment to differentiation determines tissue organization

Author

Listed:
  • Márton Demeter

    (Eötvös University
    ELTE-MTA “Lendület” Evolutionary Genomics Research Group)

  • Imre Derényi

    (Eötvös University
    ELTE-MTA Statistical and Biological Physics Research Group, Eötvös University)

  • Gergely J. Szöllősi

    (Eötvös University
    ELTE-MTA “Lendület” Evolutionary Genomics Research Group
    Institute of Evolution, Centre for Ecological Research)

Abstract

Species-specific differences control cancer risk across orders of magnitude variation in body size and lifespan, e.g., by varying the copy numbers of tumor suppressor genes. It is unclear, however, how different tissues within an organism can control somatic evolution despite being subject to markedly different constraints, but sharing the same genome. Hierarchical differentiation, characteristic of self-renewing tissues, can restrain somatic evolution both by limiting divisional load, thereby reducing mutation accumulation, and by increasing cells’ commitment to differentiation, which can “wash out” mutants. Here, we explore the organization of hierarchical tissues that have evolved to limit their lifetime incidence of cancer. Estimating the likelihood of cancer in the presence of mutations that enhance self-proliferation, we demonstrate that a trade-off exists between mutation accumulation and the strength of washing out. Our results explain differences in the organization of widely different hierarchical tissues, such as colon and blood.

Suggested Citation

  • Márton Demeter & Imre Derényi & Gergely J. Szöllősi, 2022. "Trade-off between reducing mutational accumulation and increasing commitment to differentiation determines tissue organization," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29004-1
    DOI: 10.1038/s41467-022-29004-1
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    References listed on IDEAS

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    1. Henry Lee-Six & Nina Friesgaard Øbro & Mairi S. Shepherd & Sebastian Grossmann & Kevin Dawson & Miriam Belmonte & Robert J. Osborne & Brian J. P. Huntly & Inigo Martincorena & Elizabeth Anderson & Lau, 2018. "Population dynamics of normal human blood inferred from somatic mutations," Nature, Nature, vol. 561(7724), pages 473-478, September.
    2. Laila Ritsma & Saskia I. J. Ellenbroek & Anoek Zomer & Hugo J. Snippert & Frederic J. de Sauvage & Benjamin D. Simons & Hans Clevers & Jacco van Rheenen, 2014. "Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging," Nature, Nature, vol. 507(7492), pages 362-365, March.
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