In bacteria and yeast, a gene’s importance did not predict its mutation rate, challenging the idea that evolution gives vital DNA preferential treatment.
Not all genes are equally important. Some are essential for survival, controlling basic functions such as copying DNA and keeping cells alive. Others can be lost with little or no effect. But does that mean evolution has found a way to shield its most vital genes from potentially harmful mutations?
For decades, scientists have debated whether essential genes are naturally less likely to mutate. Now, researchers at the University of Bath have put that idea to the test, with results that challenge a long-standing evolutionary hypothesis.
Dr. Sofia Radrizzani and Professor Laurence D. Hurst, from the university’s Centre for Evolution, examined spontaneous mutations in the bacterium Escherichia coli (E. coli) and baker’s yeast (Saccharomyces cerevisiae). Their study, published November 12 in PLOS Biology, found no evidence that essential genes receive extra protection and offers a new explanation for why earlier research may have suggested otherwise.
The illusion of protected genes
“We’d expect natural selection to rapidly remove mutations when they occur in more important genes, because these mutations are more likely to be harmful to the organism. This can create the illusion that important genes have fewer mutations when, in reality, some mutations have simply disappeared before we have a chance to analyze them – what you can think of as ‘ghost mutations’,” Hurst said.
To reduce that problem, the team used data from “mutation accumulation” experiments designed to minimize the effects of natural selection. Three separate tests found no evidence that selection had substantially skewed the results.
“This looks like the largest and cleanest sample of mutations assembled to date,” Radrizzani said.
Essential genes showed no extra protection
The researchers compared mutation rates with experimental evidence showing what happens when individual genes are removed. Deleting an essential gene kills the cell, while losing other genes has little or no effect. This gave the team a way to test whether genes a cell depends on most were less likely to mutate.
“Analyze the data any which way and we found nothing. In neither species did these key genes have a lower mutation rate,” Hurst said.
The team also assessed importance through the amount of a gene’s protein the cell produces and the strength of natural selection acting on the gene over evolutionary time.
“We found that genes producing more abundant proteins don’t have lower mutation rates. Nor does the way genes evolve over thousands of years predict how frequently they mutate,” Radrizzani said.
A decades-old challenge to random mutation
These findings address a debate that began in 1972 and resurfaced as recently as 2023. At stake is the relationship between the two steps in the conventional account of evolution. Mutations first generate genetic variation. Natural selection and other forces then act on that variation, favoring some traits over others.
Darwin’s finches, which Charles Darwin encountered on the Galápagos Islands in 1835, offer a familiar example. Random mutations contribute to differences in beak size, allowing birds to use different food sources. When conditions favor particular foods, birds with beaks better suited to eating them are more likely to survive and reproduce. Their traits consequently become more common over generations.
The disputed proposal suggests that a gene’s importance also influences how often mutations arise in it. Vital genes would receive greater protection, while genes where change could help adaptation would mutate more frequently. Examples of the latter include genes in which mutations give bacteria antibiotic resistance or alter birds’ beak dimensions.
There is a theoretical difficulty with that proposal. Gene mutation rates are already so low that reducing them further for individual genes would offer very little benefit, making it difficult for natural selection to favor such a protective system.
“The claim that mutation is slower for important genes is a triumph of hype over substance,” said Radrizzani, who co-wrote the paper as part of her PhD. “It’s a really old suggestion and is reinvented in various forms routinely.”
Genes copied later during DNA replication did tend to mutate more frequently in the team’s analysis, showing that some features of the genome can help explain differences in mutation rates.
“While we see known causes of variation in mutation rates, we found no evidence for the effects that have been proposed as a challenge to the conventional model. None predicted which genes would have high or low mutation rates, and there are certainly no grounds for a shift in paradigm,” Hurst said.
Reference: “The importance of genes does not predict their mutation rate” by Sofia Radrizzani and Laurence D. Hurst, 12 November 2026, PLOS Biology.
DOI: 10.1371/journal.pbio.3004089
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