Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks

New paper from Andreas Wagner & colleagues that touches on topics of perennial interest (and debate) here.

Here is the abstract in case the paper is paywalled:


Cryptic genetic variation can facilitate adaptation in evolving populations. To elucidate the underlying genetic mechanisms, we used directed evolution in Escherichia coli to accumulate variation in populations of yellow fluorescent proteins and then evolved these proteins toward the new phenotype of green fluorescence. Populations with cryptic variation evolved adaptive genotypes with greater diversity and higher fitness than populations without cryptic variation, which converged on similar genotypes. Populations with cryptic variation accumulated neutral or deleterious mutations that break the constraints on the order in which adaptive mutations arise. In doing so, cryptic variation opens paths to adaptive genotypes, creates historical contingency, and reduces the predictability of evolution by allowing different replicate populations to climb different adaptive peaks and explore otherwise-inaccessible regions of an adaptive landscape.

Here is a popular summary as well:
Tales from the crypt(ic)

Adaptation through natural selection requires inherited changes in an organism’s phenotype. However, neutral or “cryptic” mutations—changes in genotype that do not affect phenotype—can influence adaptation outcomes, because genotype-to-phenotype mapping is inherently dependent on context. The phenotypic consequence of a mutation might change as a result of interactions either with other mutations in the genome (epistasis) or with the physical environment [a genotype-by-environment (G×E) interaction]. On page 347 of this issue, Zheng et al. ( 1 ) demonstrate that the accumulation of mutations that yield neutral changes in a protein promotes faster adaptation in an environment selecting for a new function, and that this effect requires the combined impact of epistasis and G×E interactions.


The commentary by Lee and Marx is pretty good. They contrast the findings from the Science paper with those of this recent PLoS Biology paper:

I haven’t read the PLoS Biology paper, but it could be interesting to discuss how and why the two studies differ. Here is the comment from Lee and Marx:

The benefit of cryptic variation was most prominent in the first round after the transition to selection for green fluorescence. This stands in contrast to results from the in vitro evolution of a ribozyme selected for its ability to use a new substrate, in which boosts in adaptation continued through five rounds of selection ( 3 ).


Here’s a third paper on the same subject. This time they use four different β-lactamases and select for a 2nd phosphonate monoester hydrolase (PMH) activity to explore the effect of how the starting point for mutational trajectories affect the adaptive potential of the enzymes.


Genetic variation among orthologous proteins can cause cryptic phenotypic properties that only manifest in changing environments. Such variation may impact the evolvability of proteins, but the underlying molecular basis remains unclear. Here, we performed comparative directed evolution of four orthologous metallo-β-lactamases toward a new function and found that different starting genotypes evolved to distinct evolutionary outcomes. Despite a low initial fitness, one ortholog reached a significantly higher fitness plateau than its counterparts, via increasing catalytic activity. By contrast, the ortholog with the highest initial activity evolved to a less-optimal and phenotypically distinct outcome through changes in expression, oligomerization and activity. We show how cryptic molecular properties and conformational variation of active site residues in the initial genotypes cause epistasis, that could lead to distinct evolutionary outcomes. Our work highlights the importance of understanding the molecular details that connect genetic variation to protein function to improve the prediction of protein evolution.


I was trying to find more info on “cryptic genetic variation” and found this on Wikipedia:

Evolutionary capacitance is the storage and release of variation, just as electric capacitors store and release charge.

Talk about an interesting analogy. I thought car motors and molecular motors were a tough one. :smile:

More seriously, the more I dig into genetics the more crazy this stuff all sounds. It’s amazing and a little hard to believe at the same time.