If two deletions don't stop growth, try three

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Science  20 Apr 2018:
Vol. 360, Issue 6386, pp. 269-270
DOI: 10.1126/science.aat4667

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How many and which genes does an organism need at a minimum to sustain growth? With the identification of essential genes in a variety of organisms such as yeast (1), worms (2), and human cultured cells (35), the answer may seem obvious: Remove all nonessential genes, and the organism should be able to continue to survive and grow. In the yeast Saccharomyces cerevisiae, the workhorse of genetic interaction mapping, ∼1000 of the ∼6000 (∼17%) protein-coding genes are essential for viability (1). So theoretically, one might think that one could remove the other ∼5000 nonessential genes and still have a growing yeast. The reason this does not work is that genes interact with each other to drive different traits, including viability and growth. On page 283 of this issue, Kuzmin et al. (6) provide the first systematic analysis of trigenic interactions in yeast in which three gene deletions are combined in individual strains in order to ascertain the importance of multigene interactions for growth. This study shows that higher-order genetic interactions are abundant, which has implications for the interpretation of human gene variants that may interact to affect health and disease.