"To be followed by an evolving population, natural selection requires that antibiotic resistance increase with each mutation," Weinreich says. "In contrast, most mutational paths of the enzymatic variant we examined fail to continuously increase resistance. Importantly, this is not a reflection of the fact that many more mutations reduce biological function than improve it, because in the present case each mutational path is composed exclusively of mutations known jointly to improve resistance."
Weinreich argues that this finding likely applies to most protein evolution, not just the beta-lactamase enzyme.Although many mutational paths lead to favored variants, only a very small fraction are likely to result in continuously improved fitness and therefore be relevant to the process of natural selection.