Mutations are changes in the DNA sequence. Mutations can result from incorrect copying of DNA made during cell division, exposure to ionizing radiation, exposure to chemicals called mutagens, or viral infection. Germ line mutations occur in egg and sperm cells and can be passed on to offspring, while somatic mutations occur in body cells and are not inherited. 
Since the first half of the twentieth century, the theory of evolution has been dominated by the idea that mutations occur randomly with respect to their consequences. The random occurrence of mutations with respect to their consequences is an axiom on which many biological and evolutionary theories rely. This simple proposition had a profound effect on the evolutionary models developed since the modern Synthesis, shaping the way biologists have thought about and studied genetic diversity over the past century. From this view, for example, the general observation that genetic variants are found less frequently in functionally constrained regions of the genome is believed to be due only to selection after random mutation. This paradigm has been defended with both theoretical and practical arguments: that selection at the gene-level mutation level cannot overcome genetic drift; that previous evidence of a non-random mutation pattern relies on analysis of natural populations confounded by the effects of natural selection;[3-6]
On January 12, 2022, a group of researchers discovered that the genetic changes that appear in an organism’s DNA may not be completely random. This would overturn one of the key assumptions of the theory of evolution, that mutations are always random. The researchers studied a genetic mutation in a common roadside weed, thale cress ( Arabidopsis thaliana ), they found that the plant could protect the most “important” gene in its DNA from alteration, while leaving other parts of its genome to build more of it. change. 
“I was really surprised by the non-random mutations that we found, since high school biology, I was told that the mutations were random.” said lead researcher Gray Monroe, a botanist from the University of California, quoted from Live Science. 
There are many possibilities for genetic mutations and even errors to occur during the life of an organism.
“DNA is a fragile molecule; On average, the DNA in one cell is damaged between 1,000 and 1 million times each day, the DNA also has to be copied every time the cell divides, which can lead to copying errors.” said Monroe, quoted from Live Science.
Luckily for humans and all other organisms, our cells can ward off much of this damage. “Our cells are working constantly to repair DNA and have developed complex molecular machinery, DNA repair proteins, to find faults and make repairs,” says Monroe.
However, DNA repair proteins are not a foolproof solution and cannot fix all errors. “If the copy defects or errors are not repaired, they cause mutations, changes in the DNA sequence,” Monroe said.
There are two main types of mutations: somatic mutations, which cannot be passed on to offspring, and germline mutations, in which offspring can inherit DNA errors from mutated genes in their parents. Germline mutations are what trigger evolution through natural selection and become more or less common in a population based on how they affect a carrier’s ability to survive.
Not all mutations have the potential to alter an organism’s chances of survival. Mutations cause major changes in an organism only when they occur in a gene — the part of DNA that codes for a particular protein. Most of the human genome is made of non-gene DNA, Monroe said.
In the new study, the researchers decided to test for mutation randomness by investigating whether mutations occurred evenly between gene and non-gene regions of DNA in the genome of the Thale cress plant.
Thale cress is a “great model organism” for studying mutations because its genome has only about 120 million base pairs (by comparison, the human genome has 3 billion base pairs), which makes it easier to sequence plant DNA. It also has a very short life span, meaning that mutations can quickly accumulate across generations, Monroe said.
Over three years, the researchers grew hundreds of plants under laboratory conditions over several generations. In total, the researchers sequenced 1,700 genomes and found more than 1 million mutations. But when they analyzed these mutations, they found that the part of the genome containing the gene had a much lower mutation rate than the non-gene region.
“We think it’s likely that other organisms also have non-random genetic mutations,” Monroe said. “We have in fact followed up on our research by investigating this question in other species and found results indicating non-random mutations are not unique to Arabidopsis .”
However, the researchers suspect that the degree of non-randomness between different species may not be the same.
Protecting Genes is important
The non-random pattern in mutations between gene and non-gene regions of DNA suggests that a defense mechanism exists to prevent potentially catastrophic mutations.
“In genes encoding proteins important for survival and reproduction, mutations are most likely to have harmful effects, potentially causing disease and even death,” Monroe said. “Our results show that genes, and essential genes in particular, experience lower mutation rates than non-gene regions in Arabidopsis. The result is that offspring have a lower chance of inheriting harmful mutations.”
The researchers found that to protect themselves, essential genes send special signals to DNA repair proteins. This signaling is carried out not by DNA itself but by histones, special proteins that wrap around DNA to form chromosomes.
“Based on the results of our study, we found that gene regions, especially for the most biologically important genes, coil around histones with specific chemical signatures,” said Monroe. “We think this chemical signature acts as a molecular signal to promote DNA repair in this region.”
The idea of histones having unique chemical markers is not new, Monroe said. Previous studies of mutations in cancer patients have also found that these chemical markers can influence whether DNA repair proteins properly repair mutations, he added.
However, this is the first time that this chemical marker has been shown to influence mutation patterns across the genome and, as a result, evolution by natural selection.
The researchers hope their findings can eventually be used to make improvements in human medicine.
“Mutations affect human health in many ways, leading to cancer, genetic disease and aging,” Monroe said. Being able to protect certain regions of the genome from mutations could help prevent or treat these problems, he added.
However, more research into the animal genome is needed before researchers can tell if the same non-random mutation occurs in humans. “Our discoveries were made in plants and did not give rise to new treatments,” says Monroe, “but they do change our fundamental understanding of mutations and inspire many new research directions.”
The researchers also think that the chemical signals released by essential genes could be used to improve gene-editing technologies that could help us create plants that are more nutritious and resistant to climate change, Monroe said.
This finding has the potential to completely change the way we think about mutation and evolution. 
Is it because of this latest research that the theory of evolution will be wrong? The answer is of course no. This is a major discovery in 2022, and will probably change the content of school biology textbooks. But of course, big claims require great evidence, we will still wait for the results of the latest research whether non-random mutations only occur in certain species or not, prepare your seat belts.
- Mutation. National Human Genome Research Institute [https://www.genome.gov/genetics-glossary/Mutation]
- Futuyma, D. J. (1986). Evolutionary Biology 2nd. (Massachusetts: Sinauer Association)
- Lynch, M., Ackerman, M. S., Gout, J. F., Long, H., Sung, W., Thomas, W. K., & Foster, P. L. (2016). Genetic drift, selection and the evolution of the mutation rate. Nature Reviews Genetics, 17(11): 704-714.
- Stoletzki, N., & Eyre-Walker, A. (2011). The Positive Correlation between d N/d S and d S in Mammals Is Due to Runs of Adjacent Substitutions. Molecular biology and evolution, 28(4): 1371-1380.
- Hodgkinson, A., & Eyre-Walker, A. (2011). Variation in the mutation rate across mammalian genomes. Nature reviews genetics, 12(11): 756-766.
- Chen, X., & Zhang, J. (2013). No gene-specific optimization of mutation rate in Escherichia coli. Molecular biology and evolution, 30(7): 1559-1562.
- Monroe, J.G., Srikant, T., Carbonell-Bejerano, P. et al. (2022). Mutation bias reflects natural selection in Arabidopsis thaliana. Nature [https://www.nature.com/articles/s41586-021-04269-6]
- Baker, H. (2022). New study provides first evidence of non-random mutations in DNA. Live Science [https://www.livescience.com/non-random-dna-mutations]
- Ormiston, S. (2022). Genetic mutations may not be random. Front Line Genomics [https://frontlinegenomics.com/genetic-mutations-may-not-be-random/]
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