Rapid Adaptation Often Occurs through Mutations to the Most Highly Conserved Positions of the RNA Polymerase Core Enzyme

Mutations to the genes encoding the RNA polymerase core enzyme (RNAPC) and additional housekeeping regulatory genes were found to be involved in rapid adaptation, in the context of numerous evolutionary experiments, in which bacteria were exposed to diverse selective pressures. This provides a conundrum, as the housekeeping genes that were so often mutated in response to these diverse selective pressures tend to be among the genes that are most conserved in their sequences across the bacterial phylogeny. In order to further examine this apparent discrepancy, we characterized the precise positions of the RNAPC involved in adaptation to a large variety of selective pressures. We found that different positions of the RNAPC are involved in adaptation to various stresses, with very little overlap found between stresses. We further found that RNAPC positions involved in adaptation tended to be more evolutionary conserved, were more likely to occur within defined protein domains, and tended to be closer to the complex’s active site, compared to all other RNAPC positions. Finally, we could show that this observed trend of higher conservation of positions involved in rapid adaptation extends beyond the RNAPC to additional housekeeping genes. Combined, our results demonstrate that the positions that change most readily in response to well defined selective pressures exerted in lab environments are also those that evolve most slowly in nature. This suggests that such adaptations may not readily occur in nature, due to their antagonistically pleiotropic effects, or that if they do occur in nature, they are highly transient.