Capacitors of concealed genetic variability (Capacitance phenomenon)

Cryptic genetic variation (CGV) is invisible under normal conditions but fuel for evolution when circumstances change. In theory, CGV can represent a massive cache of adaptive potential or a pool of deleterious alleles in need of constant suppression. CGV emerges from both neutral and selective processes and it may inform how human populations respond to change.

An evolutionary capacitor buffers genotypic variation under normal conditions, thereby promoting the accumulation of hidden polymorphism. But it occasionally fails, thereby revealing this variation phenotypically.

The principal example of an evolutionary capacitor is Hsp90, a molecular chaperone that targets an important set of signal transduction proteins.

Experiments in Drosophila and Arabidopsis have demonstrated three key properties of Hsp90:

(1) it suppresses phenotypic variation under normal conditions and releases this variation when functionally compromised;

(2) its function is overwhelmed by environmental stress; and

(3) it exerts pleiotropic effects on key developmental processes.

Hsp90 provides a straightforward mechanism for buffering the effects of CGV. As a chaperone, Hsp90 assists in folding other proteins and in refolding misfolded proteins. Mutations in coding sequence can lead to folding error, so reduction in chaperone activity should increase the expressivity and penetrance of protein-coding mutations.

However, two main criticisms have been levied at Hsp90 as a model for releasing CGV and promoting genetic assimilation.

One is that reduction of Hsp90 activity affects biogenesis of Piwi-interacting RNA (piRNA), which in turn permits transposable element activity in the germline and can lead to de novo, heritable mutations. If new mutations account for the variation observed in Hsp90 knockdowns, then the best-studied example of CGV no longer stands.

The second criticism is that Hsp90 may be exceptional and hence not a general model for buffering. Hsp90 is an abundant protein and interacts with many molecules in the cell.

Are there other genes that can demonstrate similar buffering of standing genetic variation? And how relevant is synthetic depletion of Hsp90 to the adaptive dynamics of natural populations?


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