The creeping vole (Microtus oregoni) is an unassuming ball of fluff with a very curious arrangement of sex chromosomes. Now, researchers have found that these animals lost their Y (male) chromosome sometime within the past 2 million years, yet the species has no trouble reproducing both male and female voles.
Most mammals follow the same pattern for sex chromsomes: A pairing of two X chromosomes creates a female offspring, while an X and a Y yields a male. In creeping voles, which are native to the U.S. Pacific Northwest, it's the males that have two X chromosomes. Females have just one.
Making matters more complex, X chromosomes in both sexes carry genes that were once carried on the Y chromosome.
"It's sort of just been one surprise after another," said Polly Campbell, an evolutionary biologist at the University of California, Riverside who led the research.
The unusual sex chromosomes of the creeping vole first got attention in the 1960s, when evolutionary biologist Susumu Ohno first described the species' genetics. Ohno observed that males had paired sex chromosomes in their body cells but that only one of those sex chromosomes was ever incorporated into sperm to be passed to the next generation. Meanwhile, females had just one sex chromosome in their body cells.
Campbell and her colleagues became interested in sequencing these sex chromosomes to figure out what was really going on in creeping voles. The researchers compared the genes they found on the vole sex chromosomes with a suite of genes shared on the Y chromosome across mammals, including the prairie vole (Microtus ochrogaster), a closely related species.
They found that sometime since the creeping vole split from its closest relatives, it lost its Y chromosome. The steps that it took to make that happen are still mysterious, Campbell said, but the process likely involved Y chromosome breakage during meiosis, the process of splitting a single cell into 4 cells containing half the genetic information. These cells become sperm in males and eggs in females. In this case, the loss of the Y chromosome would have happened in male meiosis, given that males pass along the Y chromosome.
Expression and suppression
In the creeping vole, the Y chromosome may be gone, but its genes remain, clinging to the X chromosomes — even in females, the researchers found. Female voles inherit a single X chromosome from their mothers, but they don't inherit a sex chromosome from their fathers. The X chromosome they do inherit carries Y genes, but somehow the females avoid developing testes or other masculine features. Precisely how they do this isn't yet known, Campbell told Live Science.
"That's the million-dollar question," she said.
In typical male development, the expression of a gene called SRY during a precise developmental window initiates the development of testes. Female voles carry 7 intact copies of SRY, Campbell and her team found. But somehow, the female voles silence these genes and all of their consequences.
Related: See adorable photos of voles
"Really, all it takes is the evolution of some mechanism to suppress the expression of SRY or its downstream targets," Campbell said. It will take rigorous study of the embryological development of these voles to identify that mechanism, she said.
The male side of the equation is just as fascinating. Male creeping voles inherit one X from mom and one X from dad, both carrying ancestral Y genes. The paternal X will go on to be passed down in the male's sperm, but it's silenced in the male's body cells. This silencing is interesting, Campbell said, because it happens in the body cells of other female mammals: In each cell, one X is randomly shut off so that there is balance across the organism in terms of genetic instructions from each parent.
The male voles apparently do this same kind of silencing, and the researchers suspect they know how. In mammals with XX females, the X that is destined to be silenced expresses a bit of RNA called the X-inactive specific transcript, or XIST. In the voles, Campbell and her team found a mutation in the maternal X chromosome that seems to inactivate XIST. More research is needed to be sure, but it is likely that this mutation turns the silencing mechanism off in the X passed down from mom. The result is that the maternal X runs the show in the vole's body cells, while the paternal X keeps mum. The paternal X then takes center stage in the formation of sperm, a process that doesn't involve the maternal X in male voles.
Voles in the genus Microtus may have genomes that are particularly prone to interesting changes, Campbell said. They have rapid chromosomal evolution, and a large proportion of their genomes are made up of transposable elements that can move around easily and cause double-stranded breaks in DNA. The result can be new genetic arrangements as the transposable elements become incorporated in the broken segments of DNA during repair. But it's completely possible that similar rearrangements could occur in other species, Campbell said, just potentially on slower timelines.
Humans, for instance, experience sex chromosome aneuploidies, or irregular numbers of sex chromosomes. They're relatively common, and they appear in all sorts of arrangements: XXY, XO, XXX, XYY, XXYY, to name a few. While these do affect development and fertility, they're generally compatible with life, as long as at least one X chromosome is present. In contrast, aneuploidies on the other 22 pairs of chromosomes in humans almost all cause miscarriage or severe developmental defects leading to extremely short life expectancies. (Down syndrome, caused by a third copy of chromosome 21, is one notable exception.)
The survivability of sex chromosome aneuploidies "shows that these systems are flexible and dynamic, which to me is very exciting," Campbell said. With cutting-edge genetic tools available, researchers are likely to find more examples of mammals that have made unusual sex-chromosome arrangements work, she added. So far, the only known examples of mammals without Y chromosomes are creeping voles, Transcaucasian mole voles (Ellobius lutescens) and three rare species of spiny rat from Japan. But the Y chromosome isn't necessary for male and female development in plenty of nonmammalian animals, and it's less than 200 million years old in the mammalian lineage.
"I would really like this system [in voles] to be recognized not as a bizarre anomaly but as a really interesting variant on the theme of sex determination in mammals that I suspect we will find in the future is not as set as we think it is," Campbell said.
The findings were published May 7 in the journal Science.
Originally published on Live Science.
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Stephanie Pappas is a contributing writer for Live Science, covering topics ranging from geoscience to archaeology to the human brain and behavior. She was previously a senior writer for Live Science but is now a freelancer based in Denver, Colorado, and regularly contributes to Scientific American and The Monitor, the monthly magazine of the American Psychological Association. Stephanie received a bachelor's degree in psychology from the University of South Carolina and a graduate certificate in science communication from the University of California, Santa Cruz.