Scientists Solve Y-Chromosome Genetic Puzzle

Scientists have taken an important step towards understanding the human genome by completely deciphering the enigmatic Y chromosome present in males, an achievement that could help guide research into infertility.

Researchers on Wednesday revealed the first complete sequence of the human Y chromosome, which is one of the two sex chromosomes and is normally passed from parent to child. It is the last of the 24 chromosomes —threadlike structures that carry genetic information from cell to cell— in the human genome to be sequenced.

Humans have a pair of sex chromosomes in each cell. Males have one Y and one X chromosome, while females have two X chromosomes, with a few exceptions.

Y-chromosome genes help direct crucial reproductive functions, including sperm production, formally called spermatogenesis, and are even involved in the risk and severity of cancer. But this chromosome proved difficult to decipher due to its exceptionally complex structure.

“I would credit this to new sequencing technologies and computational methods,” said Arang Rhie, a scientist at the US National Human Genome Research Institute and lead author of a research paper detailing the achievement published in the journal Nature.

“It finally provides the first complete look at the code of a Y chromosome, revealing more than 50% of the chromosome length that was previously missing from our genome maps,” said Karen Miga, professor of biomolecular engineering and co-author of the study at the University of California, Santa Cruz (UCSC) and co-leader of the consortium behind the research.

The complete sequence of the X chromosome was published in 2020. But until now, the Y chromosome part of the human genome has contained large gaps.

The work revealed features of clinically relevant regions of the Y chromosome, including a stretch of DNA —a molecule that carries genetic information for the development and functioning of an organism—containing several genes involved in sperm production. The new, more complete understanding of Y-chromosome genes holds promise for practical applications, including fertility-related research, the researchers said.

“Many of these genes are important for fertility and reproduction, and especially for spermatogenesis, so being able to catalog normal variation as well as situations where it occurs, for example, azoospermia [ausência de espermatozoides no sêmen]could be useful for in vitro fertilization, as well as for further research into the activity of these genes,” said Cechova.

In addition to identifying some additional genes on the Y chromosome, the researchers discovered that some of the chromosome’s DNA had been mistaken in previous studies as being bacterial in nature.