Scheme: Wolfson Research Merit Awards
Organisation: University of Bath
Dates: Apr 2008-Mar 2013
Summary: Every new feature of a gene or genome started out as a new mutation. These new mutations may be subject to selection. Which properties of genomes are then the result of selection, what determines the mutation rate and how is adaptive evolution of the mutation rate achieved? My work has been examining these and other issues using experimental and comparative approaches. I have for example shown that in fruit flies genes that get copies late in the cell cycle tend to have higher mutation rates. This was contrary to prior evidence, but consistent with what we showed to be the case in mammals. This effect is probably due to use of a mutation prone repair process late in the cell cycle. Mutations in repair enzymes are similarly associated with high mutation rates. Bacteria when they adapt to new environments often evolve higher mutation rates by such a mechanism. It is also known that unusual “jumping genes” can also cause increased mutation rates. What I have experimentally shown with Hungarian collaborators is that when mutant versions of repair enzymes are competed with jumping genes, it is the mutant repair enzymes that usually win. This suggests that all roads to increased mutation rates are not equivalent. My research has also been addressing what features of genomes might be the result of mutation and selection and which just owing to mutation. Against expectations I showed that nucleotide usage in some bacterial genomes is driven by selection. This idea had previously been recognized as a possibility, but conventional wisdom considered the mutational model to be the more likely.