Balancing robustness and evolvability in single cells and beyond

Robustness and evolvability are defining properties of biological systems. Robustness promotes reproducibility of central biological functions, primarily by maintaining low mutation frequency and small mutational effects. By contrast, evolvability is possible only when mutations are frequent enough and lead to selectable functional effects. What is the tradeoff between robustness and evolvability? Here, we explore several cellular strategies used to regulate the balance between robustness and evolvability by modulating mutational impact or frequency. These mechanisms span the gene promoter level, biochemical pathways, single cells and whole organism levels. In particular, we discuss a recently discovered mechanism implemented at the single cell level, in which phenotypic stress-persistence and DNA damage are mechanistically coupled. This coupling increases genetic diversity specifically among individual cells that survive harsh conditions, in which evolvability may be beneficial. Taken together, these mechanisms suggest that robustness and the ability to tune mutation effects promote, rather than limit, the capacity to evolve.