members since there is not fitness cost (i.e. are within the neutral network). This represents cryptic genetic variation since if the population is newly exposed to cefotaxime, the minority members will exhibit some resistance. Chaperones Chaperones assist in protein folding. The need to fold proteins correctly is a big restriction on the evolution of protein sequences. It has been proposed that the presence of chaperones may, by providing additional robustness to errors in folding, allow the exploration of a larger set of genotypes. When chaperones are overworked at times of environmental stress, this may "switch on" previously cryptic genetic variation. Hsp90 The hypothesis that chaperones can act as evolutionary capacitors is closely associated with the heat shock protein Hsp90. When Hsp90 is downregulated in the fruit fly Drosophila melanogaster, a broad range of different phenotypes are seen, where the identity of the phenotype depends on the genetic background. Also, a recent study on the model insect, the red flour beetle Tribolium castaneum, showed that Hsp90 impairment revealed a new phenotype, reduced-eye phenotype, which was stably inherited without further HSP90 inhibition (https://doi.org/10.1101/690727). This was thought to prove that the new phenotypes depended on pre-existing cryptic genetic variation that had merely been revealed. More recent evidence suggests that these data might be explained by new mutations caused by the reactivation of formally dormant transposable elements. However, this finding regarding transposable elements may be dependent on the strong nature of the Hsp90 knockdown used in that experiment. GroEL The overproduction of GroEL in Escherichia coli increases mutational robustness. This can increase evolvability. Yeast prion [PSI+] Sup35p is a yeast protein involved in recognising stop codons and causing translation to stop correctly at the ends of proteins. Sup35p comes in a normal form ([psi-]) and a prion form ([PSI+]). When [PSI+] is present, this depletes the amount of normal Sup35p available. As a result, the rate of errors in which translation continues beyond a stop codon increases from about 0.3% to about 1%. This can lead to different growth rates, and sometimes different morphologies, in matched [PSI+] and [psi-] strains in a variety of stressful environments. Sometimes the [PSI+] strain grows faster, sometimes [psi-]: this depends on the genetic background of the strain, suggesting that [PSI+] taps into pre-existing cryptic genetic variation. Mathematical models suggest that [PSI+] may have evolved, as an evolutionary capacitor, to promote evolvability. [PSI+] appears more frequently in response to