Exploiting mutators to increase (or decrease) evolvability

An increase in mutation rate makes mutators more likely to acquire beneficial mutations and facilitates complex adaptation by increasing the probability of multiple mutations. Thus, evolvability is improved. However, this potential advantage comes with the caveat of a higher load of deleterious mutations.

In my talk, I will discuss two examples for how the resulting trade-off between high and low mutation rate can be exploited to either improve or hinder evolvability.

The first example stems from recent empirical evidence hinting that biological organisms exhibit non-genetic (epigenetic) modes of inheritance of the mutation rate. Through a combination of evolutionary modelling and simulations, I found that these observations can be rationalized by the increased rate of adaptation of populations exhibiting epigenetic inheritance of a mutator phenotype. This benefit is due to the maximized association between high mutation rate and pre-existing genetic variation, which allows for multi-step adaptation.

The second example focuses on mutagenic treatments, which act by increasing the mutation rate of pathogens, e.g. coronavirus, employing a strategy of death by mutagenesis. However, some of these treatments raise a public safety concern: could they also increase the rate of emergence of new, potentially more concerning strains of the treated pathogen? Focusing on the case study of Molnupiravir as treatment against SARS-Cov2, I will discuss the requirements for a treatment to be considered evolutionarily safe, which is the statistical assurance that the probability of emergence of concerning mutants will not be increased under mutagenic treatment.