Zebrafish sex: It’s complicated

VANDERBILT (US) — Talk about gender issues. Zebrafish don’t have a typical X and Y sex chromosome, so how to tell boys from girls?

Researchers have known that environmental factors such as water temperature can alter the proportion of males and females in a zebrafish population, but the genes involved in sex determination have remained unknown.

In a new study published in the inaugural issue of the journal G3: Genes, Genomes, and Genetics, scientists report two genes that may determine zebrafish sex.

“We were surprised that nobody knew what determined sex in zebrafish, considering where it is in the world of science,” says Jeffrey Smith, associate professor of medicine and cancer biology at Vanderbilt University.

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Using a 2,000-pound computer to mine genetic sequence, researchers identified more than 1 million genetic variants that could be used to locate genes associated with traits of interest.

“But that only works if you know where those variants reside in the genome. Location, location, location,” Smith says.

His lab has been mapping the variants on the zebrafish genome and to demonstrate the utility of the genetic resource, Smith chose to search for locations within the fish genome associated with sex determination.

Two sites were identified where the sequence significantly varied between males and females—on chromosome 5 and chromosome 16.

Within the two sites, they identified telltale changes in candidate genes dmrt1 (on chromosome 5) and cyp21a2 (on chromosome 16), both of which have been shown to play roles in sex determination in other species.

Specifically, DMRT1 has been linked to sex reversal in humans—loss of the DMRT1 gene causes a person who is genetically male (has an X and a Y chromosome) to be fully female. And mutation in the human version of CYP21A2 is one of the more common causes of hybrid sex (called pseudohermaphroditism) in humans.

But both of these loci together only accounted for about 20 percent of the variance in the trait—meaning there are other factors, perhaps several other factors, that also govern sex in zebrafish.

“These are great candidates to go forward for study as sex-determining genes in zebrafish. But demonstrating causality will be difficult because of the lack of a one-to-one correlation between inheritance and sex in zebrafish,” he says.

The most important outcome, Smith says, is the development of the genetic resource, which can be used by zebrafish researchers studying development, disease, or other traits.

“The resource is now in place. Our trait happened to be sex determination, but the same tools can be used to study any other trait of interest.”

Researchers from the University of Wisconsin, Madison contributed to the study that was supported by the National Institute of General Medical Sciences and the National Institute of Diabetes and Digestive and Kidney Disorders.

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