Evolution of extreme resistance to ionizing radiation via genetic adaptation of DNA repair
Rose T Byrne,
Audrey J Klingele,
Eric L Cabot,
Wendy S Schackwitz,
Jeffrey A Martin,
Joel Martin,
Zhong Wang,
Elizabeth A Wood,
Christa Pennacchio,
Len A Pennacchio,
Nicole T Perna,
John R Battista,
Michael M Cox
Affiliations
Rose T Byrne
Department of Biochemistry, University of Wisconsin-Madison, Madison, United States
Audrey J Klingele
Department of Biochemistry, University of Wisconsin-Madison, Madison, United States
Eric L Cabot
Genome Center, University of Wisconsin-Madison, Madison, United States
Wendy S Schackwitz
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, United States
Jeffrey A Martin
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, United States
Joel Martin
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, United States
Zhong Wang
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, United States
Elizabeth A Wood
Department of Biochemistry, University of Wisconsin-Madison, Madison, United States
Christa Pennacchio
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, United States
Len A Pennacchio
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, United States
Nicole T Perna
Genome Center, University of Wisconsin-Madison, Madison, United States; Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States
John R Battista
Department of Biological Sciences, Louisiana State University and A & M College, Baton Rouge, United States
Michael M Cox
Department of Biochemistry, University of Wisconsin-Madison, Madison, United States
By directed evolution in the laboratory, we previously generated populations of Escherichia coli that exhibit a complex new phenotype, extreme resistance to ionizing radiation (IR). The molecular basis of this extremophile phenotype, involving strain isolates with a 3-4 order of magnitude increase in IR resistance at 3000 Gy, is now addressed. Of 69 mutations identified in one of our most highly adapted isolates, functional experiments demonstrate that the IR resistance phenotype is almost entirely accounted for by only three of these nucleotide changes, in the DNA metabolism genes recA, dnaB, and yfjK. Four additional genetic changes make small but measurable contributions. Whereas multiple contributions to IR resistance are evident in this study, our results highlight a particular adaptation mechanism not adequately considered in studies to date: Genetic innovations involving pre-existing DNA repair functions can play a predominant role in the acquisition of an IR resistance phenotype.
