Replication, transcription, and translation, the pedestals of genetics, occur in synchrony. The unique machinery of each process travels along strands of DNA, replicating DNA and transcribing the information into messenger RNA to then become proteins. Normally transcription and replication travel in the same direction on the DNA highway, but what happens when instead they are on opposite sides of the road working in opposing directions?
The collision of transcription and replication in this situation can be quite dangerous, and there is no “like a good neighbor, State Farm is there” jingle to resolve the conflict. Instead, according to a new study from the Baylor College of Medicine and University of Wisconsin scientists, these collisions lead to higher rates of genetic mutations during protein production.
In their recently published
Nature paper, the researchers used model organism
Bacillus subtilis to look for patterns of mutagenesis in a specific
B. subtilis gene. They compared the rate of mutagenesis between two scenarios: DNA replication and transcription traveling in the same direction along a strand of DNA versus traveling in opposite directions, guaranteed to collide. After introducing the
B. subtilis gene into each situation, the pattern of mutagenesis was very telling.
As expected, there was a much higher mutation rate in the
B. subtilis genes that were placed in the collision scenario versus the normal, same-direction travel scenario. However, the researchers also found some unexpected results. The mutations from replication and transcription collisions, mostly insertions, deletions, and substitutions, were in the promoter region of the gene rather than in actual protein-coding sequences.
Substitution mutations involve one nucleotide base (A, C, T, G) being exchanged for another. Once switch can make a monumental difference later in the process of protein production. Additionally, as their names suggest, insertions and deletions include either an addition of a nucleotide base or the removal of a base.
Promoter sequences on strands of DNA mark the beginning of gene transcription, the molecular start line RNA polymerase relies on to begin transcribing DNA into RNA. The promoter is therefore uniquely in charge of the regulation of gene expression, and mutations in this region would lead to increased expression of a gene, decreased expression, or even complete silencing of a gene’s expression – as if it were not there at all.
Most studies usually concentrate on mutations in the protein-coding sequences, making the uncovering of promoter mutations in this study unique and promising for future genetic research. While the present study was conducted only in
B. subtilis, scientists are already looking ahead to continuing a similar study design in more bacterial species and in humans.
Sources:
Baylor College of Medicine,
Scitable by Nature Education,
University of California, Berkeley
