Research on Bizarre Rodent Genetics Solves Mystery – And Then Things Even Stranger

Taiwan campus, closely related to the creeping campus described in the study. Credit: Lai Wagtail / Flickr (CC BY-NC-ND 2.0)

Open Scott Roy’s Twitter biography and you’ll see a simple but overt phrase: “The more I learn, the more confused I get.” Now the rest of the scientific world can partake of his confusion. The most recent research by the San Francisco State University associate professor of biology, published earlier this month in one of the world’s most prestigious journals, catalogs a strange and confusing system of genes in a tiny rodent that scientists have ignored for decades.

“This is basically the strangest sex chromosome system known to science,” Roy said. “No one ordered this.” But he serves it anyway.

The owner of these chromosomes is the crawling field mouse, a tunnel rodent belonging to the Pacific Northwest. Scientists have known since the 1960s that the species has some strange genes: Their number of X and Y chromosomes (bundles of DNA which play a major role in determining sex) are far from what is expected in male and female mammals.

That finding caught Roy’s attention when presented by a guest speaker at a San Francisco State seminar, and he realized that modern technology might shed new light on the mysteries hidden in the DNA of field mice. Having worked with collaborators to free the genetic history of the field mice – resulting in one of the most completely sequenced mammalian genomes that exist, according to Roy – the story has only become alienated.

The team found that the X and Y chromosomes fused somewhere in the rodents ’past, and that the X chromosome in males began to look and act like a Y chromosome. The numbers of X chromosomes in male and female field mice have also changed, along with smaller pieces of DNA exchanged between them. The researchers published their results in Science on May 7, 2021.

Drastic genetic changes like these are exceptionally rare: The way genes determine sex in mammals is largely the same for about 180 million years, Roy explains. “Mammals, with few exceptions, are a bit boring,” he said. “Before we would have thought such a thing was impossible.”

So how did the genes of this modest rodent end up so mixed up? It’s not an easy question to answer, especially since evolution necessarily produces some sort of strangeness simply by chance. Roy however is determined to figure out the “why.” He suspects that what the team found in the field mouse genome is something like the result of an evolutionary battle for dominance between the X and Y chromosomes.

The research could not have happened, Roy says, without collaborations with Oregon fish and natural biologists who had a crawling campus sitting in a laboratory freezer. He also joined a group at Oklahoma State University when the two groups began chatting about crawling DNA sequences posted on the internet – and both realized they were working on the same issue.

Another key was to work at an educational focus institution. Roy says he has the time to develop ideas with colleagues and students at SF State, and he can explore where he doesn’t quite know what he’s going to find. “This is a great example of non-hypothesis-based biology,” Roy explained. “The hypothesis was,‘ This system is interesting. I bet if you thought about it a little more, there would be other interesting things. ‘”

It won’t be the last time Roy’s lab comes out on a limb. He and his collaborators plan to explore the genomes of other species related to field mice to map the evolutionary path that led to this strange system. He will also continue DNA sequencing curiosities through the tree of life.

“These bizarre systems give us a handshake to understand why the more common systems are like that, and why our biology works that way,” he explained. By delving into the strangest that nature has to offer, we may also be able to understand ourselves better.

Reference: “Sex chromosome transformation and the origin of a male specific X chromosome in the crawling field mouse” by Matthew B. Couger, Scott W. Roy, Noelle Anderson, Landen Gozashti, Stacy Pirro, Lindsay S. Millward, Michelle Kim, Duncan Kilburn , Kelvin J. Liu, Todd M. Wilson, Clinton W. Epps, Laurie Dizney, Luis A. Ruedas and Polly Campbell, May 7, 2021, Science.
DOI: 10.1126 / science.abg7019