Finally, the human Y-chromosome has been examined from end to end.
Researchers sequenced a chromosome from a European male, which contains genes that are involved in fertility and sperm production. The new telomere-to-telomere, or tip-to-tip, construction More than 30 million DNA base additionsTo a previously assembled Y chromosome as a reference, the team reports on online August 23. Nature. It is the last piece of the human pangenomeA project to catalogue all human DNA (SN: 5/10/23).
The Y-chromosome is one of the smallest human chromosomes. “In the old time, people thought that it’s just a junkyard for human genomic material, and it only serves one purpose … to determine male sex,” says Yun-Fai Chris Lau, a human geneticist at the University of California, San Francisco, who was not involved in the work. He says that the Y-chromosome is treated like comedian Rodney Dangerfield.
But it’s clear that the Y does more than determining male sex, Lau says. Some males are missing the Y chromosome. They are affected by the loss. at risk for cancer, Alzheimer’s disease and other illnesses (SN: 10/26/14). Researchers will be able to better understand the role of the chromosome in the human body if they have a complete reference Y Chromosome, says the researcher.
Adam Phillippy is a bioinformatics research scientist at the U.S. National Human Genome Research Institute Bethesda in Maryland, who led this project.
There are repeated sequences of DNA letters, or bases — the information-carrying building blocks of DNA — laid end to end and stretching for millions of bases like seemingly endless rows of identical puzzle pieces. The puzzle pieces of some parts of chromosomes are reversed. Some DNA stretches contain palindromes, meaning that the DNA letters are the same when read in either direction. Then, there are copies of the individual genes.
Phillippy says that all the repetition made it hard to determine where each piece went in the puzzle. So scientists saved those repetitive parts for last. “When you’re putting your puzzle back together again you always save the repetitive bits, like the grass or the trees or the sky, for the end.”
The same day, a separate study was also published on the internet. NatureThe Y chromosome of 43 people was sequenced, including 21 Africans. This study showed that the male chromosome is not fixed. The length of the varying lengthThe DNA base counts vary from person to person, which means that some people have extra copies of certain genes or DNA bits. The researchers discovered that males could have 23 to 39 copies TSPY genes involved in the production of sperm.
Phillippy’s and his colleagues were able to solve a mystery by comparing Y-chromosomes of multiple individuals. The TSPY2 gene was near the tip of the chromosome in the old reference. But the telomere-to-telomere version showed it close to the centromere — the pinched-in part of the chromosome — and backward compared with the reference.
“We confirmed that it was correct in our assembly, so then we were just assuming that it was an error in the old assembly,” Phillippy says. However, the second study confirmed that both versions were correct. TSPY2 is a chromosome that has moved around. Some people carry it in one place, and others at another.
Having multiple copies of TSPY genes, and the varying location of TSPY2, may affect the genes’ activity and effect on sperm production, Lau says. Previous studies have suggested that the number of copies can affect fertility. Other studies, however, have not found a correlation. He says that the more precise data from the new studies could help settle the debate or give researchers more information about how genes affect sperm production.
Phillippy believes that the new research could help scientists better understand the evolution of Y chromosome. He says that eventually, the study of its genes and variants could lead to a more complete understanding of infertility and fertility. However, such medical applications may be years away.
