Two X chromosomes make a girl, and boys have one X and one Y chromosome. For many of us, this is about the extent of our knowledge of sex determinism. Given the wide variety of human expression, we in our ignorance of genetics also sense that what makes a girl a girl and a boy a boy must be slightly more complicated than this. And indeed, as more detailed genomic information comes to light, this is proving to be the case. In a new study, a team of scientists discovered how a subset of miRNAs plays a key role in differentiating male and female tissues in the fruit fly.

What are microRNAs?

It’s been slightly more than a decade since scientists completed the mapping of the human genome, which resulted in a massive and unwieldy amount of raw data. Since then, researchers have been working to gain a finer understanding of all that information, while also mapping the genomes of other species. Over time, then, they have learned more about the less obvious structures contained within the genome, including MicroRNA (miRNA). Representing about four percent of the genome, miRNAs are tiny, non-protein coding genes present in virtually all animals and plants. These short segments of RNA fine-tune the activation of one or several protein-coding genes. Working in a complementary manner with one or more messenger RNA molecules, miRNA can silence or downregulate the genes they target and, in doing so, they help to orchestrate complex genetic programs that are the basis of an organism's development.

In a new study, a team of researchers at Cold Spring Harbor Laboratory — home of Dr. James D. Watson, co-discoverer of the structure of DNA — describe how miRNAs contribute to sexual differences in fruit flies. Similar to other animals, male and female flies differ visibly with females being 25 percent larger than males with lighter pigmentation and more abdominal segments. Exploring the genome, the team identified distinct miRNA populations in male and female flies, which they believe contribute to the shaping of structures that distinguish the two sexes. "In fact, miRNAs regulate the very proteins that act as sex determinants during development," said Dr. Delphine Fagegaltier, lead author on the study.

The team also found miRNAs to be essential for sex determination, even after an animal has grown to adulthood. "They send signals that allow germ cells, i.e., eggs and sperm, to develop, ensuring fertility," Fagegaltier said. "Removing one miRNA from mature, adult flies causes infertility." In fact, once the microRNA has been removed, the flies begin to produce both male and female sex-determinants, and so they lose their original sexual identity and become both male and female at once.

"This is probably just the tip of the iceberg," Fagegaltier added. "There 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." Once translated to human beings, this path of exploration might bring insight and much needed clarity to the many questions surrounding sexual identity.

Source: Fagegaltier D, Konig A, Gordon A, et al. A Genome-Wide Survey of Sexually Dimorphic Expression of Drosophila miRNAs Identifies the Steroid Hormone-Induced miRNA let-7 as a Regulator of Sexual Identity. Genetics. 2014.