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 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 RNAPC lab adaptations tended to occur at positions displaying traits associated with higher selective constraint. Specifically, compared to other RNAPC positions, positions involved in adaptation tended to be more conserved in their sequences within bacteria, were more often located within defined protein domains, and were located closer to the complex's active site. Higher sequence conservation was also found for resource exhaustion adaptations occurring within 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 often also those that evolve most slowly in nature.