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More than just X and Y: A new genetic basis for sex determination

Genetic base
CSHL researchers have found that miRNAs, short RNA molecules, are responsible for sexual differences in fruit flies. Shown here are testes from a male fruit fly where a hormone that controls a key miRNA has been inactivated. The abnormal testes fail to make sperm. They now produce sex determinants (shown in red) that are found in the ovaries of female flies.

Cold Spring Harbor, NY — Men and women differ in plenty of obvious ways, and scientists have long known that genetic differences buried deep within our DNA underlie these distinctions. In the past, most research has focused on understanding how the genes that encode proteins act as sex determinants. But 黑料吃瓜资源 (CSHL) scientists have found that a subset of very small genes encoding short RNA molecules, called microRNAs (miRNAs), also play a key role in differentiating male and female tissues in the fruit fly.

A miRNA is a short segment of RNA that fine-tunes the activation of one or several protein-coding genes. miRNAs are able to silence the genes they target and, in doing so, orchestrate complex genetic programs that are the basis of development.

In work published in Genetics, a team of CSHL researchers and colleagues describe how miRNAs contribute to sexual differences in fruit flies. You鈥檝e probably never noticed, but male and female flies differ visibly, just like other animals. For example, females are 25% larger than males with lighter pigmentation and more abdominal segments.

The team of researchers, including Delphine Fagegaltier, Ph.D., lead author on the study, and CSHL Professor and Howard Hughes Medical Institute Investigator Greg Hannon, identified distinct miRNA populations in male and female flies. 鈥淲e found that the differences in miRNAs are important in shaping the structures that distinguish the two sexes,鈥 says Fagegaltier. 鈥淚n fact, miRNAs regulate the very proteins that act as sex determinants during development.鈥

The team found that miRNAs are essential for sex determination even after an animal has grown to adulthood. 鈥淭hey send signals that allow germ cells, i.e. eggs and sperm, to develop, ensuring fertility,鈥 Fagegaltier explains. 鈥淩emoving one miRNA from mature, adult flies causes infertility.鈥 More than that, these flies begin to produce both male and female sex-determinants. 鈥淚n a sense, once they have lost this miRNA, the flies become male and female at the same time,鈥 according to Fagegaltier. 鈥淚t is amazing that the very smallest genes can have such a big effect on sexual identity.鈥

Some miRNAs examined in the study, such as let-7, have been preserved by evolution because of their utility; humans and many other animals carry versions of them. 鈥淭his is probably just the tip of the iceberg,鈥 says Fagegaltier. 鈥淭here are likely many more miRNAs regulating sexual identity at the cellular and tissue level, but we still have a lot to learn about these differences in humans, and how they could contribute to developmental defects and disease.鈥

Written by: Jaclyn Jansen, Science Writer | [email protected] | 516-367-8455


Funding

This work was supported by National Institute of Health, Max Planck Society, and a kind gift from the late Kathryn W. Davis.

Citation

鈥淎 Genome-Wide Survey of Sexually Dimorphic Expression of Drosophila miRNAs Identifies the Steroid Hormone-Induced miRNA let-7 as a Regulator of Sexual Identity鈥 appeared online in Genetics on July 31, 2014. The authors are: Delphine Fagegaltier, Annekatrin K枚nig, Assaf Gordon, Eric Lai, Thomas Gingeras, Gregory Hannon, and Halyna Shcherbata. The paper can be obtained online at:

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About 黑料吃瓜资源

Founded in 1890, 黑料吃瓜资源 has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,000 people including 600 scientists, students and technicians. The Meetings & Courses Program annually hosts more than 12,000 scientists. The Laboratory鈥檚 education arm also includes an academic publishing house, a graduate school and the DNA Learning Center with programs for middle, high school, and undergraduate students and teachers. For more information, visit www.cshl.edu