The discovery of 119-million-year-old selfish genes in yeast may change our understanding of how parasitic DNA affects genome evolution

The discovery of 119-million-year-old selfish genes in yeast may change our understanding of how parasitic DNA affects genome evolution

image: The wtf gene family of meiotic drivers has unexpectedly existed for over 100 million years
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Photo credit: Stowers Institute for Medical Research, illustration by Mark Miller

KANSAS CITY, MO – October 19, 2022 – Meiotic drivers, a type of selfish gene, are actually selfish. They are present in the genome of almost every species, including humans, and unfairly transmit their genetic material to more than half of their offspring, sometimes leading to infertility and reduced body health. Because of their parasitic potential, their longevity over evolutionary time is considered short-lived to date.

New research from the Stowers Institute for Medical Research in collaboration with the National Institute for Biological Sciences in Beijing, China, has uncovered a selfish gene family that has survived over 100 million years – ten times longer than any meiotic driver ever identified – casting new doubts on established ones Beliefs about how natural selection and evolution manage these threatening sequences.

“The thought has always been that because these genes are so bad, they won’t stay in populations for very long,” said Associate Investigator SaraH Zanders, Ph.D. “We just found out that’s not true – the genomes just can’t always get rid of them.”

Meiotic drivers are so named because they can acquire the ability to literally “drive” the transmission of their genes through a genome, often with negative consequences. Natural selection is therefore the primary force counteracting selfish genes by favoring genetic variants that kill the drive for restoring fertility and general health to a species.

“Natural selection has a limited ability to remove meiotic drivers from a population,” Zanders said. “Imagine running tryouts for football teams (natural selection) to recruit the best players (genes that promote fitness). Drivers are players who sabotage the other players trying out. Drivers make the team, but not because they are good at football.”

In a recently published study in eLife on October 13, 2022, led by researcher Mickael De Carvalho, Ph.D., of Zanders Lab, and Guo-Song Jia, a postdoctoral researcher in Li-Lin Du, Ph.D.’s lab, for the first identified time , when a family of selfish genes called wtf not only thrived in the fission yeast Schizosaccharomyces pombe, but were also passed on to three unique yeast species that split from S. pombe about 119 million years ago.

“This finding is particularly new because a family of drive genes has been thriving for at least 10 times longer than geneticists ever thought possible,” Zanders said.

During meiosis, the specialized cell division that produces reproductive cells such as sperm and ova, inheritance of genetic material from one set of chromosomes from each parent has a 50/50 or equal probability for each reproductive cell.

Meiotic drivers in yeast are actually a stronger genetic parasite. The wtf gene family are killer meiotic drivers; Not only do they transmit the selfish gene to over 50 percent of offspring, but they also destroy the reproductive cells — or spores in yeast — that don’t inherit the drive gene.

Natural selection in a genome typically saves a species from selfish genes by favoring genes that suppress or silence the drive, rendering it useless. How the wtf gene family escaped the deletion is largely due to their rapid mutation rates.

This persistence is changing our perception of how a species can overcome the expected increase in sterility that typically leads to extinction. It’s also changing the way scientists can search for and identify families of selfish genes in various species, including humans.

“Previously, when searching for driver candidates within a genome, I would not have considered “old” genes,” says Zanders. “Since selfish genes are important drivers of evolution, this new finding opens the door to thinking about how drivers can have sustained, long-term implications for genome evolution.”

Additional authors include Ananya Nidamangala Srinivasa, R. Blake Billmyre, Ph.D., Jeffery J. Lange, Ph.D., and Ibrahim M. Sabbarini.

This work was funded by the New Innovator Award from the National Institutes for Health (award: DP2GM132936), institutional support from the Stowers Institute for Medical Research, the Chinese Ministry of Science and Technology, and the Beijing Municipal Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About the Stowers Institute for Medical Research

Founded in 1994 through the generosity of American Century Investments founder Jim Stowers and his wife, Virginia, the Stowers Institute for Medical Research is a not-for-profit biomedical research organization focused on basic research. Its mission is to advance our understanding of life’s mysteries and improve quality of life through innovative approaches to the causes, treatment and prevention of disease.

The Institute consists of 17 independent research programs. Of the approximately 500 members, over 370 are research associates, including research leaders, technology center directors, postdocs, PhD students and technical support staff. Learn more about the institute at www.stowers.org and its graduate program at www.stowers.org/gradschool.

Media contact:

Joe Chiodo, director of media relations

724.462.8529

press@stowers.org


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