Are Genetic Mutations Really Random?
Observing mutation frequencies in various genes of Arabidopsis thaliana
Background
Evolutionary theory is based on the idea that genomic mutations occur randomly. This concept has shaped the study of genetics, but what if this was not actually true? This idea can be researched by observing the effects of epigenomics on mutation rates. Epigenomics is a field of genetics that studies how gene activity is regulated without altering the DNA itself.
One way gene activity can be altered is by DNA methylation. This is when methyl groups (one carbon with three hydrogens) are added to a DNA molecule. Usually, this will result in the gene being repressed. Another method seen within epigenetics involves histone modification. Histones are proteins that DNA wraps around, which allows almost six feet of it to fit inside the cell’s nucleus. Histones can be modified in various ways including methylation which will alter if the gene will be expressed or repressed. Histones also play a role in chromatin accessibility — chromatin refers to the entire complex of DNA and the histone.
The DNA structure itself can also be studied to see if it impacts the rate of mutation. One example that is studied in this article is the guanine-cytosine (GC) content. This measures the amount of G and C nucleotides that are present in a particular gene.
Summary
A group of researchers at the University of California, Davis aimed to test the classical evolutionary theory that mutations occur randomly. Their speculation that this view may not be accurate sparked from recent discoveries in biology that mutations can be influenced by various factors such as epigenomics, nucleotide composition, and DNA repair. However, there was no clear data to prove this idea, which encouraged these researchers to study it further.
In order to test if genetic mutations are truly random, scientists studied populations of mutations in the species Arabidopsis thaliana, a small flowering plant. The researchers compiled large sets of de novo mutations, which are mutations that occur for the first time. They then decided to observe if certain epigenomic characteristics, including GC content, methylation, histone modification, and chromatin accessibility, play a role in the frequency of mutations. To do this, certain genes that are known to exhibit these characteristics were observed and the rate of mutation was calculated based on variance of single nucleotides between generations.
The collected data indicated that some features demonstrated a positive or negative correlation with mutation frequency. One of these features is GC content. The results show that genes with a higher GC content (areas with high frequency of G and C nucleotides) have a lower rate of mutation. The researchers correctly predicted this as previous studies have indicated that GC rich regions are associated with more stability and high levels of DNA repair.
Another feature that showed a relationship with mutation was genes with methylated cytosine nucleotides. The data reveals that genes associated with methylated cytosines are linked to higher rates of mutation. This was also predicted as these regions have high chromatin accessibility which can weaken the ability of DNA repair mechanisms. The overall data illustrates that epigenetic factors that can impact the ability of DNA repair mechanisms are linked to a change in mutation frequency.
An additional aspect of mutation frequency that was tested was a possible correlation between mutation rates and gene function. To observe this, mutation rates were compared between gene bodies and non-coding regions. Gene bodies are parts of the gene that will be transcribed. Non-coding regions of DNA can include regulatory elements and introns which do not code for a protein and will be removed in the final mRNA transcript. Mutations were tested in 400 lines of Arabidopsis thaliana. The results indicated that gene bodies were 58% less likely to experience mutations than non-coding regions of the gene.
This was further examined by studying how mutations vary between different gene bodies. It was found that genes that code for significant biological functions, such as translation, experienced less mutations than genes that code for more specialized functions such as environmental responses. A potential cause for this relationship can be due to the content of epigenomic characteristics in these regions. The genes with high value functions demonstrated more epigenomic features that were associated with lower mutation rates while the non-coding regions contained epigenetic features associated with higher mutation rates.
The results of this experiment provide a strong challenge to the traditional view of evolution and mutation. The data clearly suggests that mutation rates can be affected by epigenetic characteristics of a gene. This study can greatly alter the way scientists study genetics in the future. It can impact how evolution and natural selection is studied and can help scientists predict where mutations can occur. Additionally, this new insight on epigenetic modifications can be utilized in gene therapy research, a field of medicine that uses genetic modifications to treat diseases. In order to gain further data and knowledge of this topic, mutation frequencies should be studied in other species.
