Should tissue structure suppress or amplify selection to minimize cancer risk?
BackgroundIt has been frequently argued that tissues evolved to suppress the accumulation of growth enhancing cancer inducing mutations. A prominent example is the hierarchical structure of tissues with high cell turnover, where a small number of tissue specific stem cells produces a large number of specialised progeny during multiple differentiation steps. Another well known mechanism is the spatial organisation of stem cell populations and it is thought that this organisation suppresses fitness enhancing mutations. However, in small populations the suppression of advantageous mutations typically also implies an increased accumulation of deleterious mutations. Thus, it becomes an important question whether the suppression of potentially few advantageous mutations outweighs the combined effects of many deleterious mutations.\n\nResultsWe argue that the distribution of mutant fitness effects, e.g. the probability to hit a strong driver compared to many deleterious mutations, is crucial for the optimal organisation of a cancer suppressing tissue architecture and should be taken into account in arguments for the evolution of such tissues.\n\nConclusionWe show that for systems that are composed of few cells reflecting the typical organisation of a stem cell niche, amplification or suppression of selection can arise from subtle changes in the architecture. Moreover, we discuss special tissue structures that can suppress most types of non-neutral mutations simultaneously.