The Y chromosome complex completely sequenced

This sequencing will certainly make it possible, in the coming years, to better understand male infertility.

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The Y chromosome (Artistic illustration)

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The Y chromosome, present only in humans, has been completely sequenced, announced the Telomere to Telomere (T2T) consortium associated with the American Human Genome Research Institute (NHGRI).

The new sequence, which fills gaps along more than 50% of the length of the Y chromosome, highlights important genomic features with implications for fertility, such as sperm production, bioinformatician Arang Rhie said in a statement. , first author of the work published in the journal Nature (New window) (in English) on August 23.

This breakthrough comes just months after T2T announced the complete, gap-free sequencing of the human genome, adding the 8% that remained to be mapped.

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A person's DNA is carried by their chromosomes.

Although it is the smallest of the chromosomes, the Y was not the easiest to decipher.

All chromosomes have repetitive regions, but the Y chromosome presented a particular challenge for traditional sequencing technologies because of its exceptionally repetitive structure, notes Professor Simon Gravel of the Department of Human Genetics at McGill University, who has not not participated in this work.

It was very difficult to understand him because everything looks the same. It was as if we had a puzzle where all the pieces were white, while in the rest of the genome the pieces had several different colors that were easier to put together.

A quote from Simon Gravel, McGill University

However, the work of the team of 100 T2T scientists made it possible to see the extent to which rehearsals are organized in the Y.

We didn't know exactly what constituted the missing sequence. It could have been very chaotic, but instead almost half of the chromosome is made up of alternating blocks of two specific repetitive sequences […]. This gives a beautiful pattern, similar to a quilt, observes Adam Phillippy, the head of NHGRI.

What is very impressive about this work is that “They've discovered lots of ways in which the Y chromosome can change in very creative ways,” says Professor Gravel.

There are duplications, there are things that disappear, there are multiple copies of the same gene that appear, there are genes that are inverted along the genome. There are all kinds of things happening that had never been measured before, because we had to develop the necessary technology to make it happen.

A quote from Simon Gravel, McGill University

< p class="StyledBodyHtmlParagraph-sc-48221190-4 hnvfyV">To successfully sequence the Y chromosome, the T2T consortium combined new DNA sequencing technologies with the latest sequence assembly methods. The knowledge gained from producing the complete sequencing of the other 23 chromosomes was also beneficial.

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The technologies used in this work are quite expensive, but they made it possible to measure the entire chromosome at once or in very few pieces, says Professor Simon Gravel.

So, to return to the image of the puzzle, it is a bit as if these works gave access to a global image which accompanies the pieces in shades of white. With an image as a reference, it became easier to reconstruct, says the professor.

The Y contains far fewer genes than the other chromosomes. And the reason is rather simple: it is only present in males and therefore cannot contain genetic information essential to both sexes.

< p class="Text-sc-2357a233-1 imohSo">If genes necessary for the constitution of the human body were not present in women, they simply would not be able to live.

A quote from Simon Gravel , McGill University

So, most of the genes on the Y chromosome are related to the development and function of the male sexual organs.

For this reason, if there is genes that do not function as they should, we expect them to be linked to male fertility, continues Professor Gravel.

The complete sequence of the Y chromosome thus reveals important information that will be used in medical research since it has, for example, a region (known as the azoospermia factor) which contains genes involved in the formation of sperm (spermatogenesis).< /p>

Its sequencing could therefore make it possible to more precisely analyze the structure associated with the azoospermia factor and its effects on sperm production.

In an article published in the same edition of the journal Nature(New window), the Human Genome Structural Variation Consortium associated with NHGRI reports the sequencing of 43 human Y chromosomes spanning 182,900 years of human evolution and exhibiting considerable diversity in size and structure, note the authors.

This work tells us how the Y chromosome evolved from its original state where it resembled the biological events that led to today's Y.

A quote from Simon Gravel, McGill University

This work is in line with the publication last May of the first reference pangenome. A pangenome represents several genomes, but contains the same number of genes [as an individual genome]. It makes it possible to distinguish different gene variants in a certain number of individuals.

In the future, this work will make it possible to go from a single reference genomic sequence (currently) to several hundred. These will illustrate more precisely the genetic similarities and differences between humans and could make it possible, among other things, to more easily detect mutations associated with thousands of hereditary diseases.

Professor Gravel and his team are interested in the evolution of the Y chromosome in the Quebec population. We are interested in genealogical data to understand mutations on the chromosome over time, says the researcher.

For example, we analyze that of several descendants of a French founding ancestor who came to Quebec 400 years ago. By tracing their lineage back to this founder and looking at the differences between these individuals, we can try to measure the rate at which the Y chromosome changes.

A quote from Simon Gravel, McGill University

< p class="StyledBodyHtmlParagraph-sc-48221190-4 hnvfyV">The present work thus represents a gold mine of information for Professor Gravel, who hopes to put it to good use.

What this work provides us is a high-resolution image of the puzzle. We can refer to it to understand, for example, in large cohorts, what mutations can cause infertility, adds the researcher.

The coming months and years will therefore be very rich in lessons. It is possible that discoveries will be jostled or that we will find that things are even more complicated than we thought, summarizes Simon Gravel.

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