Sarah Zanders, Ph.D., assistant investigator, is fascinated by selfish genes. Unlike the genes that encode for proteins crucial to healthy function of an organism, such as insulin and collagen, selfish genes “have no apparent redeeming features,” Zanders says.
They’re considered parasites, Zanders says, because they do not promote the overall fitness of the organism. Their sole function appears to be to promote their own survival by ensuring their presence in the genomes of the offspring of an organism. Selfish genes, which are the products of random mutations generating new genes, or novel variants of existing genes, can short-circuit natural selection.
“By cheating the process of sexual reproduction, selfish genes persist and spread in populations,” says Zanders.
Zanders provides a simple explanation of how selfish genes may behave during meiosis, the specialized form of cell division that creates gametes, like eggs and sperm. During meiosis, a male normally produces an equal number of sperm bearing an X chromosome as sperm carrying a Y chromosome.
Image: Courtesy of Dr. Sarah Zanders
“But, if a male has a meiotic drive gene, which is a selfish gene, on his Y chromosome, the sperm carrying that chromosome can destroy the sperm that carry the X chromosome.” As a result, when the sperm compete to fertilize an egg cell, those with the Y chromosome will have greater odds of success simply because they outnumber the sperm with the X chromosome.
Studies with yeast and other laboratory model systems have linked selfish genes with impaired fertility as well as chromosomal imbalances such as aneuploidy, which frequently occurs in cells in the early stages of cancer.
Gamete-destroying meiotic drive genes have been documented in laboratory mice but not in humans. However, Zanders says that she would not be surprised if future research indicates they also play a role in causing human infertility and aneuploidy.
Zanders became interested in selfish genes while investigating meiotic recombination, a critical step in the formation of gametes, as a graduate student at Cornell University. “I was puzzled that the genes responsible for meiosis were rapidly evolving,” she says. “The fact that the meiosis field of researchers had no satisfying explanation for their rapid evolution suggested that there was something important about meiosis that we were missing.”
While at Cornell, Zanders heard a research presentation by Harmit S. Malik, Ph.D., a scientist at the Fred Hutchinson Cancer Research Center (FHCRC). Malik spoke about the possibility that selfish genes could drive the evolution of genes including those required for meiosis. “I thought it was the best idea out there, and I wanted to explore it further.”
After receiving her Ph.D. degree in genetics and development from Cornell in 2010, Zanders joined FHCRC as a postdoctoral fellow in the basic sciences division. Malik along with FHCRC faculty member Gerry Smith, Ph.D., advised her research on fertility, genome evolution, and the origin of new species. “These three fields are all intimately associated,” she says. “Making progress in understanding one requires an appreciation of them all.”
Among her accomplishments as a postdoctoral researcher was the discovery of three independently acting meiotic drive genes in the hybrids of two fission yeasts, S. pombe and S. kambucha, which are 99.5 percent identical at the DNA level. The hybrids had very low fertility and produce few viable gametes. Their low fertility is largely the result of meiotic drive genes killing the yeast gametes that had not inherited these genes. The combined action of the three drivers and associated chromosome rearrangements keep the two yeast species reproductively isolated, says Zanders.
Her research findings, which suggest that selfish genes play a role in speciation, the evolutionary process by which biological populations evolve to become distinct reproductively isolated species, were published in 2014 in the journal eLife.
Zanders, who grew up in a small town in southwest Iowa, decided to become a scientist while an undergraduate student at the University of Iowa in Iowa City where she earned a B.S. degree in biology in 2005. “I always liked biology,” she says, “but I did not know what I would do until I took my first genetics course.”
After the final exam, the scientist who taught the genetics course, Robert Malone, Ph.D., invited Zanders to work in his lab during her free time. She accepted, and spent many hours in the lab learning about meiotic recombination and laboratory research. “I discovered that genetics is my thing,” she says. “I love it.”