The role of mitochondria on chromosomal mutation rates and antimicrobial resistance in hybrid s[...]

Mutation rate is fundamental to the evolution of all life. Mutations and selection are also the mechanisms by which microorganisms develop antimicrobial resistance. Our work has uncovered new principles about how mutation rate acts via reactive oxygen species (ROS) across microbial life. This raises the following questions:

1. What happens to mutation rate in cells with a focused source of ROS within the cell, such as yeast?
2. How do the genetics of hybrids, where only one type of parental mitochondria is retained, influence mutation rates?

There is already evidence of a strong interplay between mitochondria, environment, and mutagenesis, independent of nuclear DNA. However, understanding this interplay is challenging without manipulative experiments involving different types of mitochondria. In yeast, mitochondria are a potent internal source of ROS. Inter-species yeast hybrids, which contain nuclear genomes from two species but retain only one type of mitochondria, serve as an ideal model to study how different mitochondria affect mutation rates, evolutionary trajectories, and the acquisition of new traits (1). The environment influences which mitochondria are retained in yeast hybrids, and our research shows that the type of mitochondria impacts phenotype in an environment-dependent manner, affects complex genetic traits, and influences nuclear gene expression. Hybridization is crucial for understanding yeast speciation and has translational applications. It also offers a valuable tool for exploring fundamental cellular functions. In this project, the student will work with the Saccharomyces yeast system—using diploid and tetraploid hybrid yeasts with various combinations of nuclei and mitochondria from different species—to determine the rules governing mitochondrially driven nuclear mutation rates. This is core discovery bioscience aimed at revealing universal principles of life applicable to all eukaryotes, including humans.

Applicants should hold (or be about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in a relevant subject. Research experience in genetics and evolution is desirable.

For application details, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Interested candidates must contact the Primary Supervisor before submitting a formal application to discuss their suitability for the project. On the online application form, select PhD Genetics.

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