In nature, certain areas of the genome are protected from mutations – findings have huge implications for our understanding of gene editing as well as evolutionary theory. Report: Claire Robinson

A new scientific publication in the journal Nature shows that the occurrence of mutations (DNA damage) in plant genomes is not random and that certain areas of the genome are protected from mutations. The study also found that the occurrence and frequency of mutations in populations does not only depend on the evolutionary mechanism of random mutation and natural selection as it has traditionally been understood.

In natural selection, random mutations create new genetic variations in a gene pool. Then in the face of environmental stresses like drought or pest attack, the plants or other organisms with the "fittest" gene variations and thus characteristics get to survive and pass on their genes. This has long been assumed to be the main driver of evolution. But the new study finds that mutation in plants is not random and directionless, but biased in a direction that benefits the plant.

It’s possible to draw the conclusion from the study that evolution doesn’t just happen through chance, but seems to be driven by a more intelligent mechanism.

Unexpected finding

As a commentary on the new study in Phys.org explains, mutations occur when DNA is damaged and left unrepaired, creating a new variation. The scientists wanted to know if mutation was purely random or something deeper. What they found was unexpected.

"We always thought of mutation as basically random across the genome," said Grey Monroe, an assistant professor in the UC Davis Department of Plant Sciences who is lead author on the paper. "It turns out that mutation is very non-random and it's non-random in a way that benefits the plant. It's a totally new way of thinking about mutation."

The new study shows that there are natural mechanisms in the genome that protect specific important genomic regions from frequent mutations. So instead of randomness, the scientists "found patches of the genome with low mutation rates. In those patches, they were surprised to discover an over-representation of essential genes, such as those involved in cell growth and gene expression."

"These are the really important regions of the genome," Monroe told Phys.org. "The areas that are the most biologically important are the ones being protected from mutation."

These areas are also sensitive to the harmful effects of new mutations. "DNA damage repair seems therefore to be particularly effective in these regions," co-author Detlef Weigel said.

Findings further challenge idea that most gene editing changes could occur naturally

The new paper does not mention gene editing, but it has clear implications for the notion – much repeated by advocates of deregulation – that new GM techniques like CRISPR/Cas primarily make changes that could occur naturally. In reality, gene editing is specifically designed to override natural protections against mutations, in ways that do not happen in conventional breeding or are very unlikely to happen.

As Testbiotech explains, in gene editing, "The genetic scissors prevent the cells from restoring the original function of the gene; they can also override other natural protection mechanisms. For example, as far as applications of genetic scissors are concerned, it hardly matters where the genes are located in the genome. In addition, CRISPR/Cas also can block the function of all the backup copies of a target gene, of which there can be several in the genome of the plants.

"Plants developed with these methods can both be profoundly changed and exhibit completely new genetic combinations, even if no additional genes are inserted. Their biological traits can be clearly different in comparison to those found in conventional breeding. Therefore, the risks associated with these plants must be thoroughly assessed."

Conclusions of earlier paper confirmed

The new findings confirm those of a scientific paper published in 2019 by Dr Katharina Kawall of the Project Genetic Engineering and the Environment, which explicitly compares gene editing with conventional breeding, including techniques used with conventional breeding, namely the decades-old techniques of chemical- or radiation-induced mutagenesis. This paper showed that gene editing can make changes that would be difficult or impossible to achieve through conventional breeding, highlighting the differences between the two techniques.

Commenting on the two papers, London-based molecular geneticist Dr Michael Antoniou said, “These findings show that claims that gene editing mimics natural processes are unsupported by the scientific evidence. So trying to deregulate gene editing on the basis of its supposed ‘naturalness’ is unfounded and highly risky, as it can lead to unintended compositional changes in the product, with consequences to health and the environment.”


Further information

The new Nature publication:
Mutation bias reflects natural selection in Arabidopsis thaliana
J. Grey Monroe, Thanvi Srikant, Pablo Carbonell-Bejerano, Claude Becker, Mariele Lensink, Moises Exposito-Alonso, Marie Klein, Julia Hildebrandt, Manuela Neumann, Daniel Kliebenstein, Mao-Lun Weng, Eric Imbert, Jon Ågren, Matthew T. Rutter, Charles B. Fenster and Detlef Weigel
Nature (2022). Published 12 Jan.
https://www.nature.com/articles/s41586-021-04269-6

Phys.org report

Testbiotech comment

Project Genetic Engineering and the Environment publication