Press Release

Why a little bit of stress may protect you from your genome?

Many mutations, for example those that cause diseases in humans, only affect a subset of individuals who inherit them. New research from the CRG has investigated one cause of why this is.
Some diseases are caused by mutations that affect the three-dimensional structure of proteins, causing unstable and toxic products.  Proteins are made as a linear chain of amino acids and they have to fold, assisted by chaperones (proteins that assist the folding of other proteins or macromolecular structures), into a three-dimensional structure to function properly. Luckily, unstable proteins caused by mutations, can remain folded if there are enough chaperones around.
In conditions of high levels of stress, caused for example by heat, there are massive misfolded proteins and cell survival depends on the induction of chaperones. Researchers subjected individual Caenorhabditis elegans (round worms) to a heat shock during their larvae stage, allowed them to develop to adults and then measured the proportion of individuals affected by mutations. “Surprisingly, we found that a little bit of stress can be protective against mutations, as it does not result in cellular damage and produces enough chaperones to keep the effect of mutations in check” says Maria Olivia Casanueva, the first  author of the study.
Ben Lehner, ICREA Research professor, head of the Genetic Systems Group at the CRG and coordinator of the study says: “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.”
The study was funded by the European research Council (ERC), ICREA, the Spanish Ministry of Science and Innovation (MICINN), ERA-NET SysBio+, and AGAUR.
Reference: M. O. Casanueva; A.Burga; B. Lehner. Fitness Trade-Offs and Environmentally-induced  Mutation Buffering in Isogenic C. elegans. Science (December 16, 2011). doi: 10.1126/science.1213491
For further information: Juan Sarasua, Press Office, Public Relations and Communication Dept., Centre for Genomic Regulation (CRG). Tel. +34 93 316 02 37 -  Email: juan.sarasua@crg.eu
Images available for download at:
ftp://glligadas:gl3647as@perelman.crg.es/PRESS/Foto_Science_Ben_Lehner
NOTE:

The Genetic Systems laboratory at the CRG has recently published two other studies on how mutations combine to cause disease and how they map phenotypic changes:
- Burga A, Casanueva MO, Lehner B. Predicting mutation outcome from early stochastic variation in genetic interaction partners. Nature. 2011 Dec 7;480(7376):250-253. doi: 10.1038/nature10665.
A press release for this paper can be found here.
- Jelier R, Semple JI, Garcia-Verdugo R, Lehner B. Predicting phenotypic variation in yeast from individual genome sequences. Nat Genet. 2011 Nov 13;43(12):1270-4. doi: 10.1038/ng.1007.
A press release for this paper can be found here.