Not by Random Mutation Alone By Brian Simpson

Here is a description of scientific experiments showing that mutations are not random in the sense that the neo-Darwinian evolutionary theory provides. Mouse-ear cress (Arabidopsis thaliana), a weed with a genetic profile easy to study, was subjected to experiments. It was  found that changes bypassed certain places in the genome: those containing genes essential for cell growth and for regulating the action (expression) of other genes. “At first glance, this contradicts the theory that mutations are initially random and that natural selection determines which mutations later persist in organisms”, says Professor Detlef Weigel, head of the Planck Institute and co-author of the study.

https://oconnel.medium.com/a-common-weed-has-just-shaken-the-foundations-of-biology-4553b0b12e78

“Until now, it has been assumed that mutations — changes in the genome that occur when cells divide — are governed by chance.

“We always think of mutations as the result of random processes,” says Professor Grey Monroe, lead author of the paper in Nature. — “But it turns out that mutations are very much not random”.

DNA mutations are not random at all. They bypass key genes

Scientists studied mouse-ear cress (Arabidopsis thaliana), a common weed. It grows widely in Europe, Asia and North Africa. It has earned the nickname “laboratory rat among plants” because its genome is small and easy to study. In genetics, it is a model organism.

In the laboratories of the Planck Institute, researchers grew plants for three years. Among them were some that would not survive in nature, but in the laboratory they managed to keep them alive. Among the hundreds of plants grown, the researchers counted as many as one million different gene mutations.

Then the researchers took the trouble to see which places in the genome were mutated. To their surprise, it turned out that their distribution was not random at all. The scientists noticed that the changes bypassed certain places in the genome: those containing genes essential for cell growth and for regulating the action (expression) of other genes.

“At first glance, this contradicts the theory that mutations are initially random and that natural selection determines which mutations later persist in organisms”, says Professor Detlef Weigel, head of the Planck Institute and co-author of the study.

Natural selection causes individuals to survive whose mutations were beneficial for survival and reproduction.

What is the protection of certain genes?

How are certain areas of the mouse-ear cress DNA particularly protected against mutations? As Prof. Weigel explains, DNA repair mechanisms work efficiently in these areas, allowing the body to defend itself against changes in the genome.

Such mechanisms work in cells all the time. For studying and describing them in detail, the 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar. Sometimes, however, the repair mechanisms can’t keep up and a mutation develops in the DNA.

The researchers also found that the way DNA wraps around histones (proteins present in the cell nucleus) is a good indicator of whether or not a gene will mutate. —“This means that we can predict which genes will mutate more easily”, adds Prof. Weigel.

Plants choose which genes protect against mutations

This is a very surprising twist in the story of evolution. In a sense, plants choose which genes to protect from mutations to increase their chances of survival.

“Plants, over the course of evolution, have found a way to protect key sites in the genome from mutations. This is a very exciting discovery. You can think about how to use it to protect human genes from mutations,” adds Prof. Weigel.

Breeders rely on genetic variation — after all, new varieties are mutants of old ones. Scientists will now be able to use their newfound knowledge to more easily breed plant varieties that are resistant to pests or produce better yields.

“Our discovery provides a more complete picture of how changes occur during the course of natural selection. We think it will initiate new lines of research on the role of mutations in evolution,” the researchers conclude in the paper.

https://www.nature.com/articles/s41586-021-04269-6

Abstract

Since the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences¹. Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome—mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias² reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution."