Scientists have successfully sequenced the entire human Y chromosome for the first time, revealing new insights into its structure, function and evolution. The Y chromosome is one of the two sex chromosomes that determine the biological sex of an individual. It is present only in males and is inherited from the father.
The Y chromosome has been notoriously difficult to sequence due to its high content of repetitive DNA sequences, which make it hard to distinguish and assemble the fragments of DNA that are generated by sequencing technologies. Previous attempts to sequence the human genome left large gaps in the Y chromosome, limiting its use for studying male-specific diseases and traits.
Now, an international team of researchers from the Telomere-to-Telomere (T2T) Consortium has overcome this challenge by using advanced sequencing methods and computational tools to produce a complete and accurate reference sequence of the human Y chromosome. The study was published in the journal Nature on August 23, 20231.
The researchers used a combination of long-read sequencing, which produces longer fragments of DNA, and optical mapping, which uses fluorescent labels to visualize the DNA molecules. They also developed new algorithms to assemble and validate the sequence. They applied these techniques to a cell line derived from a male donor, whose genome has been extensively studied by the Genome in a Bottle (GIAB) consortium2.
The new reference sequence covers 57.2 million base pairs of DNA, the building blocks of the genetic code, and includes 271 genes and 156 pseudogenes, which are non-functional copies of genes. The researchers also identified 156 structural variants, which are large-scale changes in the DNA sequence, such as insertions, deletions, inversions and duplications. Some of these variants may affect gene expression or function, and could be associated with male infertility or other health problems.
The researchers also compared the new sequence with other available Y chromosome sequences from different populations and species, revealing patterns of diversity and evolution. They found that the human Y chromosome has undergone rapid changes in recent history, especially in regions that are involved in sperm production and male fertility. They also discovered that some parts of the Y chromosome are shared with other primates, such as chimpanzees and gorillas, suggesting that they have been conserved for millions of years.
The new reference sequence provides a valuable resource for researchers and clinicians who are interested in studying the role of the Y chromosome in human health and disease. It also opens new avenues for exploring the origin and evolution of sex chromosomes and sex determination in animals.
“This is really a huge shift in what’s possible,” said Monika Cechova, co-lead author on the paper and postdoctoral scholar in biomolecular engineering at the University of California, Santa Cruz3. “We hope that this will inspire more research on the Y chromosome and its impact on human biology.”