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 the cells’ commitment to differentiation, which can “wash out” mutants. Here, we explore the organization of hierarchical tissues that have evolved to limit their lifetime risk of cancer to a tissue-specific level. Analytically estimating the likelihood of cancer, we demonstrate that a trade-off exists between mutation accumulation and the strength of washing out. This result explains the differences in the organization of widely different hierarchically differentiating tissues, such as the colon and the blood.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* derenyi{at}elte.hu