Mutations often have consequences that vary across individuals. A study published in Science by Ben Lehner, head of the Genetic Systems Group at the CRG, shows that the stimulation of a stress response can reduce mutation penetrance in Caenorhabditis elegans. Moreover, this induced mutation buffering varies across isogenic individuals because of interindividual differences in stress signaling. This variation has important consequences in wild-type animals, producing some individuals with higher stress resistance but lower reproductive fitness and other individuals with lower stress resistance and higher reproductive fitness.
In the experimental setting they used a transgene to overexpress the heat shock factor 1 (HSF-1) in C. elegans, a master regulator of the environmental stress response. Then they crossed the HSF-1 transgenic animals with strains carrying diverse mutations that affect development but with outcomes that vary across individuals. In 8 out of 11 tested cases, mutation penetrance was reduced in the transgenic animals both for embryonic and postembryonic development, especially when a mutation was chaperone-dependent.
Mutations may affect the three-dimensional structure of proteins, causing unstable and toxic products. But proteins can remain stable if there are enough chaperones around, because the chaperones generally assist the folding of the linear amino acid chain into the protein and provide stability to the structure. “The levels of chaperones induced by any level of stress vary from one individual to the next, even if individuals are genetically identical. We were very excited to find that for small and protective stress levels, the stochastic fluctuation in the dose of the chaperones can partly explain why only some individuals develop the disease,” explains Ben Lehner.
Animals received a 2-hour 35°C heat shock as L1 larvae and were sorted 1 day later into “high” (right worm) and “low” (left worm) populations, according to the induction of an hsp-16.2 chaperone promoter reporter.
Casanueva MO, Burga A, Lehner B. Fitness Trade-Offs and Environmentally Induced Mutation Buffering in Isogenic C. elegans. Science. 2011 Dec 15