Research Paper Volume 6, Issue 12 pp 1033—1048

Figure 1. The proposed effect of the mutation DFE on the slope of mutation accumulation in stem cell pools with age. Lower panels, a wide DFE leads to a large fitness differential among cells in the pool. Mutations affecting phenotype are known to have mostly negative fitness effects accounting for the large negative tail in the wide DFE. Cells harboring negative mutations will be eliminated by cell competition effects. These cells are likely to be cells that have undergone a greater number of divisions and thereby possess more mutations. Consequently, mutations accumulate more slowly in the population. Upper panels: less frequent non-neutral mutations (a narrow DFE) generate less fitness differential in the pool, and thus the frequency of survival of mutated cells is dominated by drift (chance) rather than selection; the average number of mutations per cell will accumulate faster, at a rate that more closely reflects mutation occurrence and thus cell division frequency.