Study challenges evolutionary theory that DNA mutations are random
Findings could lead to advances in plant breeding, human genetics

Date:
January 12, 2022
Source:
University of California - Davis
Summary:
Researchers have found that DNA mutations are not random. This
changes our understanding of evolution and could one day help
researchers breed better crops or even help humans fight cancer.



FULL STORY ==========================================================================
A simple roadside weed may hold the key to understanding and predicting
DNA mutation, according to new research from University of California,
Davis, and the Max Planck Institute for Developmental Biology in Germany.


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

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." Researchers
spent three years sequencing the DNA of hundreds of Arabidopsis thaliana,
or thale cress, a small, flowering weed considered the "lab rat among
plants" because of its relatively small genome comprising around 120
million base pairs. Humans, by comparison, have roughly 3 billion
base pairs.

"It's a model organism for genetics," Monroe said.



========================================================================== Lab-grown plants yield many variations Work began at Max Planck Institute
where researchers grew specimens in a protected lab environment, which
allowed plants with defects that may not have survived in nature be able
to survive in a controlled space.

Sequencing of those hundreds of Arabidopsis thaliana plants revealed
more than 1 million mutations. Within those mutations a nonrandom pattern
was revealed, counter to what was expected.

"At first glance, what we found seemed to contradict established
theory that initial mutations are entirely random and that only natural selection determines which mutations are observed in organisms," said
Detlef Weigel, scientific director at Max Planck Institute and senior
author on the study.

Instead of randomness they 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 said. "The
areas that are the most biologically important are the ones being
protected from mutation." The areas are also sensitive to the harmful
effects of new mutations. "DNA damage repair seems therefore to be
particularly effective in these regions," Weigel added.

Plant evolved to protect itself The scientists found that the way DNA
was wrapped around different types of proteins was a good predictor
of whether a gene would mutate or not. "It 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 add a surprising twist to Charles Darwin's theory of
evolution by natural selection because it reveals that the plant has
evolved to protect its genes from mutation to ensure survival.

"The plant has evolved a way to protect its most important places from mutation," Weigel said. "This is exciting because we could even use these discoveries to think about how to protect human genes from mutation."
Future uses Knowing why some regions of the genome mutate more than
others could help breeders who rely on genetic variation to develop
better crops. Scientists could also use the information to better
predict or develop new treatments for diseases like cancer that are
caused by mutation.

"Our discoveries yield a more complete account of the forces driving
patterns of natural variation; they should inspire new avenues of
theoretical and practical research on the role of mutation in evolution,"
the paper concludes.

Co-authors from UC Davis include Daniel Kliebenstein, Mariele Lensink,
Marie Klein, from the Department of Plant Sciences. Researchers from the Carnegie Institution for Science, Stanford University, Westfield State University, University of Montpellier, Uppsala University, College of Charleston, and South Dakota State University contributed to the research.

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

========================================================================== Story Source: Materials provided by
University_of_California_-_Davis. Original written by Emily
C. Dooley. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. 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 AAgren, Matthew T. Rutter, Charles B. Fenster,
Detlef Weigel. Mutation bias reflects natural selection in
Arabidopsis thaliana. Nature, 2022; DOI: 10.1038/s41586-021-04269-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220112121512.htm
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