Fitness effects of rpoB mutations across a 15,000-generation adaptive trajectory

We studied whether genetic robustness can change spontaneously during adaptation to a new environment. We used a well-studied model gene where mutations are highly pleiotropic (rifampicin-resistance point mutations in the RNA polymerase). We introduced singly 10 different point mutations into each of three E. coli strains spanning 15,000 generations of adaptation from one lineage of the famous long-term evolution experiment (LTEE). We found that both deleterious and beneficial fitness effects became ameliorated in more-fit backgrounds, providing compelling evidence for the evolution of robustness, as predicted by theory.