Scientists complete human Y chromosome sequencing

According to the website of the Spanish newspaper Abesai on August 23, an international team of over 100 researchers has obtained the complete sequence of the human Y chromosome for the first time. The Y chromosome is one of our two sex chromosomes, related to male development, but so far less than half of the Y chromosome sequence can be "read". This new achievement fills numerous gaps in the length of over 50% of this chromosome, making it the last human chromosome to be sequenced by the scientific community.

First complete deciphering

Specifically, the researchers presented the complete sequence of 62460029 base pairs on the human Y chromosome. This sequence assembly corrected multiple errors in the Y chromosome in the current version of the human reference genome assembly. It also added over 30 million base pairs to the assembled version of the reference genome, revealing the complete structure of multiple gene families and confirming 41 new protein coding genes. These results also correct some hypotheses made in microbiome research, in which previously unknown human Y chromosome sequences were mistakenly interpreted as gene sequences of bacteria living in the human body.

"Now that we have a complete Y chromosome sequence, we will be able to identify and explore a large number of genetic variations that may affect human characteristics and diseases, which we could not have done before," said Dylan Taylor, an expert at Johns Hopkins University and co-author of the study

This study was conducted by a team of scientists called the Telomere to Telomere Alliance. The research results were published in two articles in the UK's Nature magazine on the 23rd.

surmount a technical difficulty

Human beings have thousands of genes, which together constitute our "manual". Genes are DNA fragments with genetic effects. Long DNA molecules, also known as chromosomes, exist in the nucleus of our cells. The information in genes is composed of four small chemical letters on chromosomes. These "letters" are called bases, and their various combinations make up all of our genetic information.

The X and Y chromosomes play important roles in sexual development in both women and men, although it has been known for many years that the factors involved in human sexual development are scattered throughout the entire genome and very complex.

20 years ago, when the first sequencing of the human genome was completed, scientists were still unable to fully "read" it, leaving almost all 23 chromosomes with "blanks". Most of these blanks are very small. Almost all of these gaps were filled by researchers from the Telomere to Telomere Alliance in a milestone statement released last year, when they added the remaining 8% of the human genome sequence that had not been decoded. These genes were unable to be sequenced 20 years ago due to a lack of necessary technology.

But more than half of the sequences on the Y chromosome are still a mystery. This greatly limits the research on the actual function of this chromosome. When scientists and doctors study a person's genome, they compare their DNA with the reference genome to determine where mutations exist. But as far as the Y chromosome is concerned, the existence of these huge gaps makes it still difficult for people to understand its mutations and related diseases.

All chromosomes have some repetitive regions, but the duplication of the Y chromosome is unusual, making sequencing particularly difficult to complete. Collecting sequencing data is a bit like reading a book cut into strips. If all the sentences in the book are unique, it will be easier to determine their order. But if the same sentence is repeated thousands of times, the original order will not be so clear. Although all human chromosomes contain repetitive sequences, there are approximately 30 million letters on the Y chromosome that are repetitive sequences. It's like more than half of the book is repeating the same sentence.

To address this issue, the telomere to telomere alliance has applied a series of new DNA sequencing techniques and sequence assembly methods, as well as knowledge gained from generating the first gapless sequence of 22 other human chromosomes.

Medical significance is significant

"The most surprising thing is that the degree of organization in the duplicated parts is quite high," said Adam Filipi, one of the leaders of the alliance. "We didn't know exactly what the missing sequence was composed of before. It could have been very chaotic, but in contrast, almost half of the chromosomes are composed of two specific repeated sequence blocks called 'satellite DNA' alternating. They form a beautiful pattern."

The complete sequence of the Y chromosome reveals important features of regions of medical significance. For example, one of the regions called the "azoospermia factor region" contains some genes known to be related to sperm production. Thanks to the newly completed sequencing, researchers were able to study the structure of a set of reverse repetitive sequences in the "azoospermia factor region".

Dr. Alan Riye, the first author of one of the papers published in the journal Nature, said, "This structure is very important because these 'palindrome' structures sometimes form DNA loops. Sometimes, these loops are accidentally cut, resulting in deletions in the genome. This may alter sperm production and affect fertility."

This undated image provided by the National Institute of Human Genomics in the United States shows the output of the DNA sequencer.