neutral network - senecio7の日記

Marx CJ 2011 Regulatory revolution: evolving the "anti-LacI" repressor. Cell 146:350-352.

five mutations in the β-lactamase gene increased bacterial resistance by ∼100,000-fold
each mutation's contribution was rather violently affected by which other mutations were present
this resulted in a rugged adaptive landscape that blocks most possible paths to the fittest allele
in contrast, two recent studies (Chou et al., 2011; Khan et al., 2011) found that epistatic interactions between beneficial mutations in multiple genes were dramatically more gentle than those within genes
instead of intense, erratic interactions, there was a general trend of diminishing returns
on this smooth adaptive landscape, every possible trajectory to maximal fitness would be selectively accessible
epistasis contributed substantially to the deceleration of adaptation
the study by Poelwijk and colleagues represents an interesting intermediate case in which the mutations occur within a single protein, LacI, but selection acts upon the "functional" proteins that it regulates
as with β-lactamase, the observed interactions are quite strong
unlike with β-lactamase, all trajectories to the most-fit genotype of LacI require at least one mutational step that is neutral (i.e., that doesn't change the regulatory logic) but that is ultimately necessary for a synergy with mutations later in the evolutionary process
this contingency of a complex phenotype upon earlier, enabling mutations draws parallels to another study examining the evolution of E. coli populations to metabolize citrate
this study and the one now presented by Poelwijk and colleagues provide examples in which variation within a neutral network of genotypes, all with equivalent phenotypes, is critical to finding a region in that network that could access more fit phenotypes
the observation of a barrier to adaptation, or a "constraint," thus appears to have followed directly from the fact that only one (or a few) mutations could enable the needed switch in logic and that to reach this logic requires a pair of subsequent mutations that are individually neutral
this challenge for adaptation is perhaps best thought of as a "statistical constraint," rather than some immutable consequence of physical laws