A new milestone for pertomics 😂

The finding that genetic suppressors are highly conserved across genetic contexts is potentially reassuring for the development of therapeutics that mimic genetic suppressors. More details on all of this in the paper. If you have any comments, please let me know!

Almost every suppressor that she studied could rescue the TS mutant in all genetic backgrounds. Despite this high conservation, the fitness of the mutants, and thus the “strength” of the suppression, did vary across the genetic backgrounds

Claire used yeast as a model to study the conservation of genetic suppression. She isolated suppressors of temperature sensitive (TS) mutants, and then tested whether the suppressors could still rescue the TS mutants if she moved them into other, genetically diverse backgrounds

Sometimes the detrimental effects of a disease mutation can be rescued by another mutation. Such suppressor mutations may identify new therapeutic targets, but these would be more useful if their protective effect would occur in many, genetically diverse patients

Thanks to the teams @fbm-unil.bsky.social @unil.bsky.social @umasschan.bsky.social and collaborators @leopoldparts.bsky.social‬ @ptck72.bsky.social @markashe.bsky.social
@nicolo-tellini.bsky.social Gianni Liti, Andrei Chabes, and all lab members without Bluesky accounts!

Finally, we explored the importance of the mapped modifiers for evolutionary trajectories in natural populations. Using a set of >1,000 yeast isolates, we show that modifier variants may allow the accumulation of otherwise deleterious mutations in the bypassed essential genes

The identified modifiers are quite different from spontaneous bypass suppressor mutations that were isolated in a laboratory. These differences are likely due to the deleteriousness of the laboratory suppressor mutations, suggesting that these are unlikely to become fixed in natural populations

In most cases, a single gene was responsible for the change in essentiality. This genetic “simplicity” is somewhat surprising given the focus on complex genotype-to-phenotype relationships in scientific literature, but can be explained by the rare and extreme nature of the phenotype we are studying

We selected 18 natural yeast strains, whose genomes are about as different from each other as those of two human beings, and asked whether ~800 genes that are required for viability in a laboratory yeast strain were also essential in these wild yeast strains. We found 39 genes that were not

Many studies have identified differences in gene essentiality between genetically distinct individuals or organisms. But, the genetic causes (“modifiers”) that are underlying these differences often remain unknown. Here, we set out to systematically identify such modifiers in the budding yeast