Effects of mutation rate and bias on bacterial adaptive dynamics

Abstract

The impact of an enhanced mutation rate on evolutionary dynamics is extensively studied. For instance, mutator genotypes with high mutation rates speed up adaptation by increasing the supply of beneficial mutations. Many mutators also have altered mutation biases. Thus, mutation rate and bias are often entangled. However, how altered mutation biases affect the fate of mutators, or evolutionary dynamics generally, is not well understood. Recently, previous work in the lab showed that reversing ancestral bias can allow populations to access previously under-sampled mutational space, including beneficial mutations. An important prediction from our work is that mutators that reverse ancestral bias should be able to adapt to a novel environment faster than mutators that reinforce ancestral bias. For instance, if an ancestor was transition-biased, transversion-biased mutators should adapt faster than transition-biased mutators. Here, using E. coli mutators, we study the adaptation of an ancestral (wild-type) population. On comparing mutators with similar (intermediately high) mutation rates, we indeed find that mutators with a reversed bias adapt faster than mutators with a reinforced ancestral bias. However, we find substantial variation in the rate and extent of adaptation of mutators with similar mutation rates (or biases), suggesting that additional factors contribute to these dynamics. Future directions include testing these effects at lower mutation rates, as well as other consequences of altered bias. Our work shows preliminary evidence that changes in mutation rate and bias could jointly determine access to mutational space, influencing adaptive dynamics, the genetics of adaptation, and ultimately genome evolution.