The human Y chromosome has been fully sequenced for the first time

Twenty years after the Human Genome Project was declared full, the Y chromosome has been absolutely sequenced for the primary time.

Most folks have 22 pairs of chromosomes plus two intercourse chromosomes – both a pair of X chromosomes or one X and one Y chromosome. Having a Y often – however not at all times – ends in an embryo creating male traits.

The Y is likely one of the smallest chromosomes and has the fewest genes coding for proteins. Because it usually has no paired chromosome to swap items with previous to sexual copy, it’s particularly more likely to accumulate bits of repetitive DNA.

All early strategies of DNA sequencing concerned breaking DNA up into small items, studying their genetic code after which reassembling the items by in search of overlaps. This method doesn’t work with repetitive DNA the place plenty of the items are equivalent.

Because of this, the “completed” human reference genome introduced in 2003 was really removed from full. “The Y chromosome just kept being pushed aside,” says Charles Lee on the Jackson Laboratory for Genomic Medicine in Connecticut. “It’s a hard chromosome to complete because of all the repetitive sequences.”

Only in 2021 did a workforce together with Karen Miga on the University of California, Santa Cruz, lastly fill in virtually all of the gaps, and once more declare the human genome full.

What made this doable is a way, developed by an organization known as Oxford Nanopore, that reads the sequence of a single DNA molecule because it goes via a tiny gap, producing items which are hundreds of thousands of DNA letters lengthy fairly than a number of hundred.

But the “complete” genome sequenced by Miga and her colleagues was a feminine one, consisting of the 22 regular chromosomes and the X chromosome. Only now have Miga’s workforce accomplished the Y chromosome as effectively, from an individual of European descent.

“The Y chromosome is riddled with complicated structures and includes huge areas where the same blocks of code repeat over and over with minor variations, making its assembly quite challenging,” says Sergey Nurk, who labored on the challenge earlier than getting a job at Oxford Nanopore. “[The] ability to sequence any-length fragments of DNA was absolutely instrumental for this project.”

This full Y chromosome has 106 protein-coding genes, which is 41 greater than within the reference genome. But each one of these additional genes are simply copies of 1 gene known as TSPY.

At the identical time, Lee’s workforce has sequenced the Y chromosomes of 43 various males, together with 21 of African origin. The groups had been unbiased however did collaborate, says Lee.

However, solely three of his workforce’s Y sequences are gapless, he says. The relaxation nonetheless have between one and 5 gaps.

The 43 Y chromosomes present appreciable variety, says Lee. For occasion, the variety of copies of the TSPY gene ranges between 23 and 39.

Whether the repetitive DNA within the Y does something necessary stays unclear. “I believe there’s a lot to learn about repetitive DNA and we just don’t understand it yet, and so we’ve still dismissed it as junk,” says Lee.

But most biologists and clinicians have little curiosity within the repetitive DNA, says David Page on the Massachusetts Institute of Technology, who research the Y chromosome. The sequencing has additionally revealed little or no that’s new in regards to the “euchromatic” components of the Y that do embrace genes, he says.

“The present study [by Miga’s team] represents an incremental advance in our understanding of the euchromatic portions, which were nearly complete 20 years ago,” says Page.