Think of your DNA as a pile of Legos. These Legos come in four different colors—and each one has a corresponding letter: A, C, T, and G. When you pair them together in different ways, you can get all kinds of different humans. Sometimes, they pair in very different ways from most other people.
This can result in genetic mutations. While these differences can often be harmless, sometimes they’re not—resulting in things like diseases and disabilities just because a Lego was put in the wrong spot.
That’s why scientists have long sought after human genome sequencing, the process of understanding the full order of the bases of DNA (those A, C, T, and G Legos). While the first human genome sequence was mapped in 2001, it wasn’t complete or accurate. Luckily, a lot has advanced in the more than 20 years since then.
ADVERTISEMENT
In 2022, an international group of scientists called the Telomere-to-Telomere Consortium announced that they were able to finally fill in the gaps of the human genome. Today, they have published a paper of their findings focused on the Y chromosome in the journal Nature. It is the last human chromosome to be fully sequenced and offers a window into understanding male evolution and the genetic quirks that can affect males—and potentially lead to cures and treatments.
“It was the Y chromosome that lacked the most sequences from the previous reference genome,” lead author Arang Rhie, a staff scientist at the National Human Genome Research Institute, said in a statement. “It was always irritating knowing we were missing half the Y whenever we tried to do any reference-based analysis. I was really excited to curate the first complete Y, to see what we were actually missing, and what we can now do.”
The reason the Y chromosome was so elusive is due to its relatively complex structure. Unlike most other chromosomes, the Y is made up of palindromes, or sequences that are the same forward and backward. These palindromes are long too—roughly more than a million base pairs.
As such, the human genome reference that scientists and clinicians use to compare with a person’s genome was incomplete. This makes it difficult to suss out exactly what certain genetic issues might be causing problems.
Technology has advanced a lot since the human genome reference was first created though. Using computers capable of long-read sequencing, the team was able to add more than 30 million base pairs to the reference. They also identified 31 new protein-coding genes, which are proteins that provide instructions to our DNA for how they should be assembled.
These new methods allow researchers a greater understanding into how the Y chromosome impacts health and human evolution. For example, scientists found new features of one section of the chromosome dubbed the azoospermia factor region, which is involved in sperm production.
“This structure is very important because occasionally these palindromes can create loops of DNA,” Rhie said. “Sometimes, these loops accidentally get cut off and create deletions in the genome.”
In a separate but related paper also published in Nature, researchers were able to sequence the Y chromosome from 43 different males across 21 world populations. This gives great insight into human genetic evolution—along with even more information to help with medical treatments and diagnostics.
“Research is emerging that shows proper Y chromosome gene function is incredibly important for the overall health of men,” senior author Charles Lee, a researcher at The Jackson Laboratory for Genomic Medicine in Connecticut, said in a statement. “Our study enables the inclusion of the full Y chromosome in all future studies when sequencing male genomes to understand health and disease.”
