No need to rewrite Darwin’s theory of evolution, study finds

The largest analysis of its kind finds no evidence that important genes are protected from mutation, challenging claims that our established understanding of evolution needs to be rewritten.

The idea that important genes mutate less frequently than others was first proposed in 1972 as a challenge to the traditional view of evolution. But the claim has remained contentious. Now, new research from the University of Bath finds the evidence behind it to be flawed.

In a new paper published today in PLOS Biology, Dr. Sofia Radrizzani and Professor Laurence D Hurst, from the University’s Centre for Evolution, analyzed the largest collection to date of spontaneous mutations in two microorganisms: the bacterium Escherichia coli (E. coli) and the single-celled fungus baker’s yeast (Saccharomyces cerevisiae).

The researchers say their study debunks the idea that natural selection might protect important genes by reducing their mutation rates – a theory that has repeatedly resurfaced since it was first proposed 44 years ago, most recently in 2023.

“The claim that mutation is slower for important genes is a triumph of hype over substance,” said Dr. Radrizzani, who co-wrote the new paper as part of her PhD. “It’s a really old suggestion and is reinvented in various forms routinely.”

Evolution as a two-step process

Classically, evolution is seen as a two-step process. First, mutations generate genetic variation. Then, forces such as natural selection act on that variation, favoring some traits over others. In other words, natural selection is like a sieve that traps larger objects while letting finer ones through.

Darwin’s finches – first encountered by Charles Darwin on the Galápagos Islands in 1835 – provide a famous example: differences in the finches’ beaks allow them to exploit different sources of food. While random mutation generates beaks of different sizes, when conditions favor particular foods, birds whose beaks are better suited to them are more likely to survive and reproduce, making those traits more common over generations.

However, some researchers argue that mutation may not be as random as traditionally assumed and that important genes (such as those involved in replicating DNA or maintaining basic cellular machinery) are protected from mutation, while genes where change could aid adaptation (such as those in which mutations give bacteria resistance to antibiotics, or change beak dimensions) mutate more frequently.

The idea that organisms might protect important genes from mutation seems helpful. If mutations in an important gene are likely to cause serious harm or genetic disease, why would evolution not reduce that gene’s mutation rate?

However, there are theoretical problems with this idea. Gene mutation rates are already so low that reducing them further for individual genes would bring very little benefit, making it difficult for natural selection to favor such a system.

The problem of ‘ghost mutations’

Previous studies may also have underestimated how often important genes mutate.

Professor Hurst said: “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’.”

Mutation accumulation

To overcome these problems, the researchers used data from ‘mutation accumulation’ experiments in E. coli and baker’s yeast, designed to minimize the effects of natural selection. Three separate tests found no evidence that natural selection had substantially skewed the results.

Dr. Radrizzani said: “This looks like the largest and cleanest sample of mutations assembled to date.”

The researchers then asked whether important genes really do mutate less often. They compared mutation rates with experimental evidence showing what happens when individual genes are removed. Some genes are essential, meaning that removing them kills the cell, while the loss of others has little or no effect.

Professor Hurst said: “Analyze the data any which way and we found nothing. In neither species did these key genes have a lower mutation rate.”

The team also considered other ways of measuring a gene’s importance, including how much of its protein a cell produces and the strength of natural selection acting on it over evolutionary time.

Dr. Radrizzani said: “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.”

Structural features do matter

The researchers did, however, find, that some features of the genome can affect mutation rates - for example, genes copied later during DNA replication tend to mutate more frequently.

Professor Hurst said: “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.”