New research has revealed evolutionary hotspots in DNA tangles where mutations are more likely to occur.
Mutational hotspots describe instances where independent cell lines persistently fix mutations at the same genomic sites, which can make evolution remarkably repeatable. These regions are important as they have been shown to drive evolution across various domains of life from viruses (such as SARS-CoV-2) and bacteria to human cancers. Our understanding of evolutionary dynamics (e.g., competitive selection) can help explain the appearance of hotspots. However, the genetic features that build such hotspots by biasing mutation rates are not as clear.
There are three primary facilitators of mutational hotspots that drive repeatable evolution including: (1) Fixation bias, (2) Mutational accessibility and (3) Mutation bias. Nonetheless, the importance of the genetic sequence in driving parallel evolutionary outcomes is unknown.
Determining highly repeatable evolution
In a recent study, published in Nature Communications, researchers from the Milner Centre for Evolution aimed to identify the key features that build mutational hotspots. They specifically investigated the evolution of two strains of the soil bacteria Pseudomonas fluorescens (SBW25 and Pf0-1). Although these strains share homologous genetic backgrounds, previous work has observed that they evolve divergently.
The team found that when they removed a gene that enables the bacteria to swim, both strains were able to quickly evolve the ability to swim again. However, each strain used quite different routes. The SBW25 strain always mutated the same part of a particular gene to regain mobility. Whereas the Pf0-1 strain mutated different places in various genes each time the researchers repeated the experiment.
To further explore this evolutionary disparity, the team compared the DNA sequences of the two strains. Here, they found that the SBW25 strain, which mutated in a predictable manner, harboured a region (ntrB locus) where the DNA strand looped back on itself forming a hairpin-shaped tangle. These tangles were able to disrupt DNA polymerase and increase the likelihood of mutations. When removing these structures, using six synonymous mutations, the team were able to abolish the mutational hotspot. This led the bacteria to evolve in a much wider variety.
The role of silent variation
This work highlights the role for silent genetic variation in determining adaptive outcomes. It shows that while natural selection is still the most important factor in evolution, it is clear that other factors can also play a role too.
Dr Tiffany Taylor, from the Milner Centre for Evolution, said:
“If we knew where the potential mutational hotspots in bacteria or viruses were, it might help us to predict how these microbes could mutate under selective pressure.”
This information could help scientists better understand how bacteria and viruses evolve. As a result, this could help develop vaccines against emerging variants of disease. It may also help predict how microbes might develop antibiotic resistance.
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