Bath study of E. coli and yeast finds no lower mutation rate in essential genes

Sofia Radrizzani and Laurence D. Hurst from the Centre for Evolution at the University of Bath analysed spontaneous mutations in the bacterium Escherichia coli and baker's yeast Saccharomyces cerevisiae. The study was published on 12 November in PLoS Biology. The authors found no evidence that more important genes mutate less often than others plos.orgPLoS Biologyplos.orgOpen source ↗.

What was tested

The conventional view treats mutation as a random process. Since 1972, and again as recently as 2023, it has been challenged by proposals that selection shaped differences in mutation rate between genes. According to these claims, important genes are protected from mutation, in prokaryotes partly by lying on the leading strand of DNA replication. Genes needed for rapid adaptation would mutate more often, partly by lying on the lagging strand.

The earlier claims proved contentious and several replications failed. However, none of the replication attempts fully accounted for covariates, and many used data from mismatch repair (MMR) knockout strains.

The team used accumulated mutation accumulation data for wild-type strains, a design meant to minimise the effect of natural selection. They predicted mutational density, in mutations per base pair, from several controlled parameters. Gene importance was captured by protein level and essentiality; in E. coli, the replication strand was also considered. Observed correlations were compared with values expected from trinucleotide-controlled simulations plos.orgPLoS Biologyplos.orgOpen source ↗.

What was found

In neither species did genes for more abundant or essential proteins have lower mutation rates. In E. coli, more highly transcribed genes may have slightly lower rates, which could fit a selectionist model, but this was not seen in yeast.

In E. coli there was no difference in mutation rate between genes on different strands, and the same lack of difference was replicated in other prokaryotes. The degree of purifying selection acting on a gene did not predict its mutation density either.

The authors also describe a strong artefact produced by the standard off-the-shelf statistical approach, and note that results from MMR-deficient strains are discordant with the rest. In the Bath analysis, genes copied later in DNA replication tended to mutate more often, a known source of variation in mutation rates plos.orgPLoS Biologyplos.orgOpen source ↗.

The authors conclude that the trends are nearly uniformly unsupportive, inconsistent between species and of minuscule effect size, so they present no challenge to the conventional model.