Y chromosome fully sequenced for the first time, revealing its secrets from 'telomere-to-telomere'

Scientists have decoded the Y chromosome in full for the first time.

In a new article published Aug. 23 in Nature, scientists with the Telomere-to-Telomere, or T2T, consortium—a group of researchers affiliated with the U.S. National Institutes of Health’s National Human Genome Research Institute—described how they used advanced DNA sequencing technology to reveal previously hidden areas of the Y chromosome.

“With the full sequence of a human Y chromosome, we now know what the Y looks like from telomere-to-telomere,” author Monika Cechova, Ph.D., a postdoc at the University of California, Santa Cruz, told Fierce Biotech Research in an email.

If you’re a bit confused by this news, you’re not alone. After all, didn’t the T2T consortium just say last year that they’d fully sequenced the human genome?

In general, that is still accurate, Cechova said. Women typically have two X chromosomes, though there are exceptions. The Y chromosome, found in males, intersex people and some females, isn’t present in about half the population—and, because it’s smaller in size, has fewer genes and is passed on from father to offspring in a unique way, it hasn’t been studied as much as it should be. 

“The way I think about this is similar to the first man on the Moon, who was considered the first human on the Moon,” Cechova said. “In practical terms, finishing the Y chromosome required tremendous additional (and manual) effort. Y wasn’t part of the material used by the T2T consortium initially, and likely a general improvement in the technology was needed as well to fully complete it.”

Large portions of the Y chromosome have long been inaccessible to scientists, namely on account of what’s known as satellite DNA, stretches of short sequences of nucleotides repeated over and over again. On top of that, the chromosome also contains many palindromes, sequences of different nucleic acids that are the same forward and backward, like the words “kayak” and “civic.” These, too, were once challenging to decode.

But DNA sequencing technology—like long-read sequencing techniques—has advanced significantly over the past few years, as have algorithms and other methods to work with repetitive parts of the genome. That’s made it possible to study regions of the Y chromosome that are dense with satellite DNA, such as an arm called Yq. Decoding this region and studying its function would have been “unimaginable” just a few years ago, she said.

In the Yq arm, lifting the veil revealed some unexpected patterns.“It was surprising for us how organized it was [the different types of satellite DNA] and deprived of other elements, such as transposable elements, that are ubiquitous elsewhere in the genome,” Cechova said.

Now that the Y chromosome is fully sequenced, scientists will be able to include it in genomewide association studies, which are used to study the relationship between genes, traits and disease. They’ll build a database of variants and medically relevant genes and rearrangements, hechova explained, which will help them understand issues like loss of sperm production.

A complete Y chromosome sequence will help shed light on one of its biggest mysteries: why it disappears with age.

“It will be interesting to learn more about this process, and the associated health consequences, using the full Y chromosome,” Cechova said.

Editor's note: This article has been updated to correct the spelling of Cechova's last name.