Dangerous selfish genes: new study

Research published by the Stowers Institute for Medical Research includes important insights into how a dangerous selfish gene works and survives.

According to the authors of the work, research on selfish genes could one day be used to fight diseases, especially those that can be transmitted between insects, animals and humans.

These genes are described by researchers as “parasitic”.

Selfish gene elements are sequences of nucleotides, which are part of the building blocks of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) that replicate in the genome.

Although tiny, these genomes are capable of killing an organism, the researchers say.

POISONS AND ANTIDOTES

The study published last week builds on previous research on a driver gene found in yeast, a sort of selfish gene that can replicate at higher rates than most other genes, but provides no benefit to the organism.

Called “wtf4”, this gene is capable of producing a toxic protein that can destroy all offspring.

For a given parent’s cellular chromosome pair, “drive” is only achieved when wtf4 is only on one chromosome.

As a result, there is only rescue of offspring that inherit the “drive” allele. its allele is one of two or more versions of the DNA sequence at a given genomic location, through the administration of a dose of a similar protein that actually neutralizes the poison, called an ‘antidote’.

In simpler terms, these genes are capable of poisoning the surrounding offspring in such a way that only those who are similar can survive.

NEW DISCOVERIES

This new study, published in PLoS Genetics, discovered how the same selfish gene uses this poison-antidote strategy to facilitate its own function, as well as its long-term evolution.

What the US-based researchers found is that differences in the timing of the generation of venom and antidote proteins, and their unique distribution patterns in spore development are integral to the drive process.

The study involved yeast, not humans or animals, but these spores are reproductive cells that would be the equivalent of an egg or sperm.

The researchers developed a model to further examine how the poison works to kill the spore, and their results showed that toxic proteins clump together, potentially disrupting the proper folding of other proteins essential to cell function.

Notably, since the wtf4 gene carries both the position and the antidote, the antidote is so similar in shape that it clusters with the poison.

The antidote, however, has an extra part that the researchers reported, which appears to isolate the poison-antidote clusters by directing them to the vacuole, the cell’s trash equivalent.

Researchers looked at the beginning of the spore formation process to find out how selfish genes act during the reproductive process and found that the toxic protein was present in all developing spores, as well as the sac around them, where it was only visible at low concentration.

As development progressed, the antidote was enhanced in spores that had inherited wtf4 from the parent yeast cell.

Through this examination, the researchers discovered that spores that inherited the driver gene created more antidote proteins inside the spore to counter the poison, thereby ensuring their survival.

HOW THE RESEARCH CAN BE USED

This deeper understanding of this poison-antidote strategy is important for scientists studying similar fields, such as those designing synthetic drive systems for pathogenic pest control, such as ways to eradicate harmful pests. .

Better knowledge of these dynamics could lead to an end to pest populations that harm crops, or even humans, in the case of vector-borne diseases, which are diseases caused by viruses, bacteria or parasites transmitted to humans by animals or insects. .

“It’s quite dangerous for a genome to encode a protein that has the ability to kill the organism,” Stowers associate researcher SaraH Zanders, Ph.D., said in the study’s press release. “However, understanding the biology of these selfish elements could help us build synthetic engines to alter natural populations.”

Another example, from former predoctoral researcher Nicole Nuckolls, involved a specific pest.

“If we could manipulate these DNA parasites to express them in mosquitoes and cause them to kill, that could be a way to control pest species,” Nuckolls said.