Dangerous selfish genes: new study

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

According to those behind the work, the research into selfish genes could one day be used to fight diseases, especially those that can be transferred between insects, animals and humans.

These genes are described by researchers as “parasitic.”

Selfish gene elements are nucleotide sequences, which are among the building blocks of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) that replicate themselves within the genome.

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

POISON AND ANTIDOTES

The study published last week built on past research on a driver gene found in yeast, a kind 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 able to produce poison protein which can destroy all offspring.

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

As a result, there is a rescue of only the offspring that inherit the “drive” allele. his allele is one of two or more versions of DNA sequence at a given genomic location, through the delivery of a dose of a similar protein which actually counteracts the poison, called the “antidote.”

In more simple terms, these genes are able to poison surrounding offspring in a way that only those that are similar are able to survive.

NEW FINDINGS

This new study, published in PLoS Genetics, has uncovered 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 was that differences in the timing of the generation of both the poison and the antidote proteins, and their unique distribution patterns in developing spores 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 cell.

The researchers developed a model to further examine how the poison functions to kill the spores, and their results showed that poison proteins cluster together, potentially disrupting the proper folding of other proteins that are essential for the functioning of the cell.

Notably, as the wtf4 gene carries both position and antidote, the antidote is so similar in form that it groups together with the poison.

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

The researchers examined the start of the spore formation process in order to find out how selfish genes act during the reproductive process, and found that the poison protein was present within all the developing spores, as well as the sac around them, where it was only seen in a low concentration.

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

Through this examination, the researchers found that the spores that inherited the driver gene created more antidote protein inside the spore to counteract the poison, ensuring their survival.

HOW THE RESEARCH MAY BE USED

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

Further knowledge of this drive could lead to putting an end to pest populations that harm crops, or even humans, in the cases of vector-borne diseases, which are diseases caused by viruses, bacteria or parasites that are transmitted to humans from animals or insects .

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

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

“If we could manipulate these DNA parasites to be expressed in mosquitoes and drive their destruction, it may be a way to control pest species,” Nuckolls said.