In my own view, the most interesting aspect of the recent Lenski paper is its highlighting of the pitfalls that Darwinian evolution must dance around, even as it is making an organism somewhat more fit. (1) If the “wrong” advantageous mutation in topoisomerase had become fixed in the population (by perhaps being slightly more advantageous or more common), then the “better” selective pathway would have been shut off completely. And since this phenomenon occurred in the first instance where anyone had looked for it, it is likely to be commonplace. That should not be surprising to anyone who thinks about the topic dispassionately. As the authors note, “Similar cases are expected in any population of asexual organisms that evolve on a rugged fitness landscape with substantial epistasis, as long as the population is large enough that multiple beneficial mutations accumulate in contending lineages before any one mutation can sweep to fixation.” If the population is not large enough, or other factors interfere, then the population will be stuck on a small peak of the rugged landscape.
This fits well with recent work by Lenski’s and others’ laboratories, showing that most beneficial mutations actually break or degrade genes (4), and also with work by Thornton’s group showing that random mutation and natural selection likely could not transform a steroid hormone receptor back into its homologous ancestor, even though both have very similar structures and functions, because the tortuous evolutionary pathway would be nearly impossible to traverse. (5, 6) The more that is learned about Darwin’s mechanism at the molecular level, the more ineffectual it is seen to be.