The nonessentiality of essential genes in yeast provides therapeutic insights into a human disease

• DOI: 10.1101/gr.205955.116
• Publication Date: 2016-07-21T02:49:12Z
• Authors: Piaopiao Chen; Dandan Wang; Han Chen; Zhenzhen Zhou; Xionglei He
• Keywords: Loss function

Essential genes refer to those whose null mutation leads lethality or sterility. Theoretical reasoning and empirical data both suggest that the fatal effect of inactivating an essential gene can be attributed either loss indispensable core cellular function (Type I), gain side effects after losing dispensable periphery II). In principle, inactivation Type I rescued only by re-gain functions, whereas II could a further another eliminate otherwise effects. Because such loss-of-function rescuing mutations may occur spontaneously, become nonessential in few individuals large population. Motivated this reasoning, we here carried out systematic screening for essentiality yeast Saccharomyces cerevisiae . Large-scale whole-genome sequencing essentiality-reversing mutants reveals 14 cases whereby is on gene. particular, encoding enzyme adenylosuccinate lyase (ADSL) shown II, suggesting therapeutic strategy human disorder ADSL deficiency. A proof-of-principle test nematode Caenorhabditis elegans shows promising results.