Nature: DNA tangles can help predict the evolution of mutations

According to a new study by the Milner Center for Evolution at the University of Bath, untangled DNA tangles can create mutation hot spots in the bacterial genome

Although most evolution is determined by natural selection, and only those individuals who have adapted to the environment can survive and pass on their genes, a new study published in the journal Nature Communications shows that Evolution is also affected by the entanglement of DNA strands

A team of scientists led by the University of Bath and the University of Birmingham observed the evolution of two soil bacteria Pseudomonas fluorescens (SBW25 and Pf0-1)

When scientists removed a gene that allows bacteria to swim, both bacteria quickly evolved the ability to swim again, but they used very different routes

One strain (called SBW25) always mutates the same part of a specific gene to regain mobility

However, every time the scientist repeated the experiment, another strain (Pf0-1) mutated at a different location in a different gene

To understand why the evolution of one strain is predictable and the other is unpredictable, they compared the DNA sequences of the two strains

These tangles disrupt the cellular machinery called DNA polymerase, which replicates genes during cell division, making mutations more likely to occur

When the research team used six silent mutations (which did not change the protein sequence produced) to remove the hairpin structure, the mutation hotspot disappeared, and the bacteria began to evolve in a broader way to restore their ability to swim

Dr.

"We found that there are some hot spots in the DNA, where the sequence causes the separated DNA strands to re-entangle together-kind of like when you pull a strand of rope, it causes tangles

"When DNA polymerase runs along the DNA strand to replicate a gene, it hits the tangles and jumps over, causing mutations

"Our experiments show that we can create or eliminate mutation hotspots in the genome by changing the sequence, thereby causing or preventing hairpin tangles

"This shows that although natural selection is still the most important factor in evolution, there are other factors at play

"If we know where the potential mutation hotspots of bacteria or viruses are, this may help us predict how these microorganisms will mutate under selective pressure

Mutation hotspots have been found in cancer cells, and researchers plan to look for mutation hotspots in a range of bacterial species, including important pathogens

This information can help scientists better understand how bacteria and viruses evolve, which can help develop vaccines against new variant diseases
.
It also makes it easier to predict how microorganisms will become resistant to antibiotics
.

Dr.
James Horton recently completed his Ph.
D.
at the Milner Evolution Center.
He said: “Like many exciting discoveries, this was discovered by accident
.
The mutations we observe are so-called silent mutations because they It does not change the protein sequence produced, so initially we thought they were not particularly important
.

"However, our findings fundamentally challenge our understanding of the role of silent mutations in adaptation
.
"

DOI

10.
1038 / s41467-021-26286-9

Article title

A mutational hotspot that determines highly repeatable evolution can be built and broken by silent genetic changes