Evolution at a high imposed mutation rate

Wilcox, A., 2017. Evolution at a high imposed mutation rate. PhD, Nottingham Trent University.

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Mutation is an evolutionary process that provides much of the genetic variation required for natural selection and genetic drift. The mutation rate is a major driving force behind evolution, but is also an evolved characteristic itself. Although there is much theoretical research into why it evolved to the rate it did, there is little experimental work that investigates how its alteration affects evolution.
I created a novel system in which bacteriophage ΦX174 could be evolved at a mutation rate two orders of magnitude higher than wild-type. This system used a defective proofreading gene in the host polymerase to cause mutagenesis, and did not require the use of external mutagens which often conferred a biased mutational spectrum and harmful non-mutagenic effects.
Replicate populations of ΦX174 were evolved in both wild-type and mutagenic conditions for approximately 300 generations. One mutagenic population displayed a faster rate of adaptation than the wild-type lines, acquiring many of the same adaptive mutations in a shorter time frame, and rapidly increasing in fitness. While the wild-type lines were characterised by periodic selective sweeps of individual mutations, the mutagenic conditions allowed many of these mutations to rise in frequency due to a single selective sweep. The other mutagenic population, however, evolved very differently, with an early decrease in fitness that it did not recover from. This population acquired many mutations not seen in the other lines, and lacked many of the common adaptive mutations.
The mutation rate increase was not high enough to cause extinction of the viral population. The vastly different outcomes for the two replicate populations show that while an elevated mutation rate can in turn increase the rate of adaptation, it can also prevent it altogether by altering the genetic background and "locking out" potential adaptive mutations through negative epistasis.

Item Type: Thesis
Creators: Wilcox, A.
Date: July 2017
Rights: This work is the intellectual property of the author, Alexander Wilcox. You may copy up to 5% of this work for private study, or personal, noncommercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the owner(s) of the Intellectual Property Rights.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 02 Feb 2018 10:03
Last Modified: 02 Feb 2018 10:03
URI: https://irep.ntu.ac.uk/id/eprint/32610

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