Characterizing the Distribution of Epistatic Effects Using A Sequence-Based Assay in Escherichia Coli
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Epistasis, the modification of the fitness effects of a mutation by other mutations, has important consequences for the trajectory of adaptive evolution and for the shape of the “adaptive landscape”. Nonetheless, the extent of epistasis, and the shape of the distribution of epistatic effects (DoEE), are poorly characterized. We developed a high-throughput method for describing the DoEE. A set of 4123 E. coli ORFs (the ASKA collection) was transformed into a strain bearing a common antibiotic resistance mutation, and into a wild-type strain. Upon induction of expression, the fitness of each ORF was determined using a sequence-based assay, providing a rapid measure of background-dependent fitness effects for over 4000 constructs. 216 epistatic interactions were detected. Synthetic dosage lethal/sick interactions from the over-expression of yiaN and nfi were validated using 24 hour growth curves, and may indicate that these genes are potential targets for drug design.
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Copyright © 2014 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
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- 2014
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