Y Marks the Spot

Winter 2024

A photo of a an old brown map showing the pathway to the letter Y.

The chromosome associated with male development—the last mysterious piece of the human genome—has been fully sequenced by a global team of more than 100 researchers, including those at Johns Hopkins.

The achievement, published in Nature, completes the Y chromosome’s genetic code and unveils details that could provide a clearer picture of the role the chromosome plays in male-specific development, fertility, and genetically triggered diseases like cancer.

The DNA sequence comprising chromosomes encodes the genes andgenetic circuits that guide the development and function of all cells in living organisms. New sequencing technology and bioinformatics algorithms allowed the team to decode the Y chromosome, which has been challenging due to its repetitive molecular patterns.

The team revealed the structures of sperm-regulating gene families and discovered 41 additional genes in the Y chromosome. They also unveiled the structures of genes thought to play significant roles in the growth and functioning of the male reproductive system.

“We completed the wiring diagram for all these genetic switches that get activated via the Y chromosome, many of which are critical to the genetic contributions to male development,” said author Michael Schatz, a Bloomberg Distinguished Professor in computer science, biology, and oncology. “We are at a point where scientists can start using this map. We were previously blind to different parts of the genome and different mutations, but now that we can see the whole genome, we hope we can add new insights to the genetics of a lot of different diseases.”

The Y chromosome, along with the X chromosome, is often discussed for its role in sexual development. While these chromosomes play a central role, the factors involved in human sexual development are spread across the genome and very complex, giving rise to the array of human sex characteristics found among male, female, and intersex individuals. These categories are not equivalent to gender, which is a social category. Additionally, recent work demonstrates that genes on the Y chromosome contribute to other aspects of human biology, such as cancer risk and severity.

The research was led by the National Human Genome Research Institute, part of the Telomere-to-Telomere consortium that in 2022 unveiled the complete sequence of a human genome.

Other Johns Hopkins authors are Rajiv McCoy, Dylan Taylor, Paul Hook, Winston Timp, Steven Salzberg, Nae-Chyun Chen, Ariel Gershman, Jakob Heinz, Stephen Hwang, Michael Sauria, Alaina Shumate, and Samantha Zarate.

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