A human X (left) and Y chromosome seen with a scanning electron microscope
BIOPHOTO ASSOCIATES/Science Photograph Library
Twenty years after the Human Genome Mission was declared full, the Y chromosome has been absolutely sequenced for the primary time.
Most individuals 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 all the time – leads to an embryo creating male traits.
The Y is among the smallest chromosomes and has the fewest genes coding for proteins. As a result of it usually has no paired chromosome to swap items with previous to sexual replica, 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 on the lookout for overlaps. This method doesn’t work with repetitive DNA the place a lot of the items are similar.
Due to this, the “accomplished” human reference genome introduced in 2003 was really removed from full. “The Y chromosome simply saved being pushed apart,” says Charles Lee on the Jackson Laboratory for Genomic Medication in Connecticut. “It’s a tough chromosome to finish due to all of the repetitive sequences.”
Solely in 2021 did a crew together with Karen Miga on the College of California, Santa Cruz, lastly fill in nearly all of the gaps, and once more declare the human genome full.
What made this doable is a way, developed by an organization referred to as Oxford Nanopore, that reads the sequence of a single DNA molecule because it goes by means of a tiny gap, producing items which might be thousands and thousands of DNA letters lengthy moderately than just a few hundred.
However the “full” genome sequenced by Miga and her colleagues was a feminine one, consisting of the 22 regular chromosomes and the X chromosome. Solely now have Miga’s crew accomplished the Y chromosome as nicely, from an individual of European descent.
“The Y chromosome is riddled with difficult constructions and consists of big areas the place the identical blocks of code repeat time and again with minor variations, making its meeting fairly difficult,” says Sergey Nurk, who labored on the mission earlier than getting a job at Oxford Nanopore. “[The] capability to sequence any-length fragments of DNA was completely instrumental for this mission.”
This whole Y chromosome has 106 protein-coding genes, which is 41 greater than within the reference genome. However each one of these further genes are simply copies of 1 gene referred to as TSPY.
On the similar time, Lee’s crew has sequenced the Y chromosomes of 43 numerous males, together with 21 of African origin. The groups had been impartial however did collaborate, says Lee.
Nonetheless, solely three of his crew’s Y sequences are gapless, he says. The remaining nonetheless have between one and 5 gaps.
The 43 Y chromosomes present appreciable variety, says Lee. For example, the variety of copies of the TSPY gene ranges between 23 and 39.
Whether or not the repetitive DNA within the Y does something necessary stays unclear. “I imagine there’s lots to study repetitive DNA and we simply don’t perceive it but, and so we’ve nonetheless dismissed it as junk,” says Lee.
However most biologists and clinicians have little curiosity within the repetitive DNA, says David Web page on the Massachusetts Institute of Know-how, 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 embody genes, he says.
“The current research [by Miga’s team] represents an incremental advance in our understanding of the euchromatic parts, which had been practically full 20 years in the past,” says Web page.
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