FLICKR, ZEISS MICROSCOPYResearchers had long suspected that silencing one gene could cause secondary effects elsewhere in the genome. But just how widespread these “secondary mutations” are was largely left to conjecture. Now, a team led by investigators at the Johns Hopkins University School of Medicine in Baltimore, Maryland, has shown that perturbation of any single gene in the yeast genome is sufficient to drive subsequent genetic changes. The team’s results were published today (November 5) in Molecular Cell.
“Certainly people had seen secondary mutations before in these yeast strains, but I think what’s special is the prevalence of them,” said Stanford University’s Michael Snyder, who was not involved in the work. The study, he added, shows that “a very large number of knockouts have a secondary mutation—much higher than I would have guessed.”
J. Marie Hardwick and her colleagues were exploring cell death mechanisms in yeast when they first noticed genomic variability among cells of Saccharomyces cerevisiae knockout strains. Comparing cells derived from the caf4-deletion strain, Xinchen Teng—then a postdoc in Hardwick’s lab and now an associate professor at Soochow University in China—first ruled out contamination or incorrect knockout construction as potential sources of the variation. Further tests showed that stochastic fluctuations in ...
