Study challenges evolutionary theory that DNA mutations are random

Researchers have found that DNA mutations are not random. A simple roadside weed may hold the key to understanding and predicting DNA mutations, according to a new study from the University of California at Davis and the Max Planck Institute for Developmental Biology in Germany.

The findings, published Jan. 12 in the journal Nature, radically change our understanding of evolution and could one day help researchers breed better crops or even help people fight cancer.

Mutations occur when DNA is damaged and not repaired, creating a new variation. Scientists wanted to find out if mutation was a purely random phenomenon or if it was something deeper. What they discovered was unexpected.

“We had always thought that mutations occurred almost randomly in the genome,” says Gray Monroe, associate professor of plant science at the University of California, Davis, and lead author of the paper. “It turns out that mutation is very non-random, and it’s non-random in the sense that it benefits the plant. It’s a whole new way of looking at mutation.”

The researchers spent three years sequencing the DNA of hundreds of plants of Arabidopsis thaliana, or watercress, a small flowering weed that is considered the “lab rat among plants” because of its relatively small genome of about 120 million base pairs. Humans, by comparison, have about 3 billion base pairs.

“It’s a model organism for genetics,” Monroe says.

Laboratory-grown plants produce many variations

The work began at the Max Planck Institute, where researchers grew samples in a protected laboratory environment that allowed plants with defects that might not have survived in nature to survive in a controlled environment.

Sequencing of hundreds of Arabidopsis thaliana plants revealed more than 1 million mutations. Within these mutations, a non-random pattern was found that contradicted expectations.

“At first glance, what we found contradicts the well-established theory that initial mutations are completely random and that only natural selection determines which mutations are observed in organisms,” says Detlef Weigel, scientific director of the Max Planck Institute and senior author of the study.

Instead of randomness, they found regions of the genome with low mutations. In these areas, they were surprised to find an overrepresentation of important genes, such as genes involved in cell growth and gene expression.

“These are really important regions of the genome,” Monroe said. “The areas that are most biologically important are protected from mutations.

These regions are also susceptible to the damaging effects of new mutations. “Therefore, DNA damage repair seems to be particularly effective in these regions,” Weigel added.

The plant evolved to protect itself

Scientists have found that the way DNA is wrapped around different types of proteins is a good predictor of whether a gene will mutate or not. “This means we can predict which genes are more likely to mutate than others, and it gives us a good idea of what’s going on,” Weigel said.

The findings put an unexpected twist on Charles Darwin’s theory of evolution by natural selection because they show that the plant evolved to protect its genes from mutation to ensure survival.

“The plant has evolved a way to protect its most important places from mutations,” Weigel said. “It’s very interesting because we can use these discoveries to think about how to protect human genes from mutations.”

Future applications

Knowing why some regions of the genome mutate more than others can help breeders who rely on genetic variation to breed better crops. Scientists can also use this information to better predict or develop new treatments for diseases such as cancer caused by mutations.

“Our findings provide more insight into the forces driving the patterns of natural variability; they should inspire new lines of theoretical and practical research into the role of mutation in evolution,” the paper concludes.

Co-authors from the University of California, Davis: Daniel Kliebenstein, Marielle Lensink, and Marie Klein of the Department of Plant Sciences. Researchers from the Carnegie Institution of Science, Stanford University, Westfield State University, University of Montpelier, Uppsala University, College of Charleston and South Dakota State University contributed to the study.

Funding came from the Max Planck Society, the National Science Foundation, and the German Research Foundation.

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