Breaking bad: Evolution by loss-of-function

Paradoxically, the first step adaptation to a new environment often involves losing genes, rather than gaining new ones—a phenomenon observed across the tree of life. Adaptation via loss-of-function is common in microbial evolution for diverse selective pressures, e.g. novel carbon sources (Gifford et al. 2016), toxins such as antibiotics (Gifford et al. 2018) and new host environments (Winstanley et al. 2016). Despite the ubiquity of this process, we know little about environment shapes loss of gene function, and the consequences of different loss-of-function mutations for organismal fitness. Understanding evolution via loss-of-function will help us understand these important processes in natural selection, but will also have practical applications in, e.g. bioengineering, where preventing microbes from losing introduced genes is critical.

We have identified key environments in which adaptation occurs via loss-of-function mutations, but unlike for other forms of variation, we have little knowledge about the repeatability of such changes, their relative contribution to adaptation, and their knock-on effects for survival and adaptation in other environments. For example, do different loss-of-function mutations—such as frame-shifts or gene deletions—occur at different rates? Are they functionally equivalent? Do they have different consequences for microbial fitness, both in the environment in which they arose, and also in other environments?

Microbial experimental evolution offers the tools and throughput needed to uncover these processes over evolutionary time. We will expose strains of the genus Pseudomonas (Hesse et al. 2018) to different environments (carbon sources, sub-lethal antibiotics) and to new genomic contexts (introduction of an energetically-costly genetic construct) in which adaptation via adaptive loss-of-function has previously been observed. Genomic and experimental tools, including high-throughput sequencing and fitness assays in diverse environments, will enable us to address clear hypotheses, filling important gaps in our current knowledge on this key adaptive process.

Candidates with experience and/or an interest in evolutionary biology, microbiology, and/or genomics are encouraged to apply.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

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For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk