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University of Bath: important genes in E. coli and yeast do not mutate more slowly

Analysis of the largest collection of spontaneous mutations in E. coli and baker's yeast found no lower mutation rates in important genes, contrary to a theory proposed in 1972.

University of Bath: important genes in E. coli and yeast do not mutate more slowly
Photo: Joydeep, Wikimedia Commons, CC BY-SA 3.0 · License: CC BY-SA 3.0

Researchers at the University of Bath's Centre for Evolution found no evidence that important genes mutate less often than others, according to a paper published in PLOS Biology and reported by eurekalert.org eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗. Dr Sofia Radrizzani and Professor Laurence D Hurst analysed the largest collection to date of spontaneous mutations in the bacterium Escherichia coli and the single-celled fungus baker's yeast, Saccharomyces cerevisiae.

The idea that natural selection protects important genes by lowering their mutation rates was first proposed in 1972. It has resurfaced repeatedly over 44 years, most recently in 2023.

Why earlier evidence was doubtful

The hypothesis holds that genes for DNA replication or basic cellular systems are shielded from mutation, while genes where change could aid adaptation mutate more often. The authors point to a theoretical problem: gene mutation rates are already so low that reducing them further for individual genes would bring very little benefit, so selection would struggle to favour such a system.

Previous studies may also have underestimated how often important genes mutate. Selection quickly removes harmful mutations, which can create the illusion of fewer mutations in important genes. Professor Hurst calls these "ghost mutations" eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

What the new analysis showed

The team used data from mutation accumulation experiments, designed to minimise the effects of natural selection. Three separate tests found no evidence that selection had substantially skewed the results.

The researchers compared mutation rates with experimental data on what happens when individual genes are removed. Some genes are essential, and their loss kills the cell, while the loss of others has little or no effect. In neither species did essential genes have a lower mutation rate.

The authors also considered other measures of importance: how much of its protein a cell produces and the strength of natural selection on a gene over evolutionary time. Genes producing more abundant proteins did not have lower mutation rates, and the way genes evolve over thousands of years did not predict how often they mutate eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

Some genome features did affect mutation rates. For example, genes copied later during DNA replication tend to mutate more frequently. According to Professor Hurst, none of the proposed effects predicted which genes would have high or low mutation rates.

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