Lurking within the genomes of nearly all species—including plants, fungi, and even humans—are genes that are passed from generation to generation with no clear benefit to the organism. Called “selfish” genes, they can sometimes be harmful or even lethal. A recent study from the Stowers Institute for Medical Research sheds new light on how selfish genes cheat inheritance to ensure they are passed to the next generation, often at the expense of an organism’s fertility.

Selfish genes operate by driving or favoring their own transmission during reproduction. The most extreme class, called killer meiotic drivers, create toxic proteins that destroy reproductive cells—except for those that inherit the gene that are saved by also making a protein antidote.

This research expands on a previous study describing how one wtf gene (wtf4) is passed on from generation to generation. The current study, led by Predoctoral Researcher Ananya Srinivasa Nidamangala from the Zanders Lab, explored whether all functional wtf genes—there are hundreds—rely on similar molecular mechanisms and which protein features were necessary for function.

Several key discoveries emerged. The killing ability of wtf genes originates from the way Wtf poison proteins aggregate or form clusters. Their matching antidotes also cluster together, and the poison and antidote must co-assemble to rescue developing gametes, or reproductive cells. These self-assembly properties resemble those of other proteins capable of forming toxic clusters, such as those implicated in neurodegenerative diseases.

The dynamic interplay of sabotage and salvation lends an almost cinematic touch to yeast’s evolutionary plot. The rapid evolution of wtf drivers have enabled them to outrun suppressor genetic elements for over 100 million years. However, the researchers found that mutations can and do occur in nature, giving rise to “self-killing” gene copies that totally destroy fertility of organisms carrying the gene.

A major driver of rapid genome evolution are genetic conflicts,” Zanders further explained. “Understanding the conflicts introduced by wtf genes is shedding light on fission yeast genome evolution, but similar dynamics, similar arms races, similar conflicts are happening throughout other organisms and have shaped our own genomes as well. This study opens the door for future research into how protein aggregation influences infertility, evolution, and disease.

Source: https://www.stowers.org/news/stowers-scientists-uncover-principles-underlying-the-toxicity-of-selfish-genes