It reveals important details that sharpen the role the Y chromosome plays in male development, fertility and genetic diseases such as cancer.
In humans, each cell usually contains one pair of sex chromosomes. Males have one X and one Y chromosome, while females have two X chromosomes. For decades, researchers have struggled to determine the sequence of the Y chromosome because of its complex structure. But now they bring big news. After all, scientists succeeded in deciphering the genetic code of the Y chromosome, the last human chromosome not yet sequenced.
It’s an enormous challenge to decode the Y chromosome. This is because part of the DNA is organized into what are called homologues: long sequences of identical forward and backward sequences. To make matters worse, these symmetries can also extend to more than a million base pairs. All chromosomes contain some repeating regions, but the Y chromosome is extraordinarily frequent, which makes sequencing particularly challenging. About 30 million letters of the Y chromosome are repeated.
Repeated regions in the Y chromosome
Collecting sequencing data is like reading a long book sliced into strips. If all the rules in the book are unique, then it is relatively easy to determine the order in which the rules should be. However, if the same sentence is repeated thousands or millions of times, the original order of the strips is, as you can imagine, much less clear. Although all human chromosomes contain repeats, the Y chromosome, as mentioned, is really a duplicate. It is as if the same few sentences are repeated for about half the length of the book.
It is no coincidence that the Y chromosome has remained a mystery for so long. “Just a few years ago, half of the human Y chromosome was missing,” says researcher Monica Cechova. “At the time, we didn’t even know if it could be sequenced, it was very confusing.” In order to identify the notorious repetitive fragments, the researchers used new DNA sequencing techniques and methods in the study. Along the way, the team made a startling discovery.
“The big surprise was how organized the returns were,” said Adam Phillippe, a co-author of the study. “We didn’t know exactly what the missing sequence consisted of. It would have been very messy. But instead, about half of the chromosome is made up of alternating blocks of two specific repeat sequences. It produces a beautiful quilt-like pattern.”
30 million additional base pairs
This means that the male Y chromosome has finally been deciphered. And for the first time, this elusive part of the genome has also been fully mapped. With this, the researchers add at least 30 million new base pairs to the human genome repertoire. Also, 41 hitherto unknown genes have been discovered in the Y chromosome. This is crucial new insight for those studying important questions of reproduction and evolution.
What about that? To understand genomic differences between people, researchers in the past have developed a reference sequence of the human genome that is used as a “standard”. This first (almost) complete sequence of the human genome was considered the blueprint for all humans at the time. When scientists and doctors study a patient’s genome, they usually compare that person’s DNA with that of that standard reference to determine exactly where the differences are. Unfortunately, the Y chromosome portion of the human genome contains large gaps, making it difficult to understand the diversity and associated diseases.
But researchers have now changed that. The new sequence fills in gaps greater than 50% of the length of the Y chromosome. This reveals important genetic features that have implications for fertility, such as sperm production factors. Indeed, the newly completed sequencing allows researchers to study the structure of a series of homologues in a distinct segment of the Y chromosome, a stretch of DNA that contains several genes known to be involved in sperm production. “This structure is very important, because these analogues can sometimes create DNA loops,” said researcher Arang Ri. “Sometimes these loops are accidentally cut and deletions occur in the genome.” It is known that this can interfere with sperm production. Thus, these symmetries affect fertility. With the complete Y chromosome sequence on hand, researchers can now analyze these deletions and their effects on sperm production more accurately.
In addition, complete Y chromosome sequencing provides more knowledge about evolution. In fact, the Y chromosome is the fastest changing human chromosome, and even the fastest changing chromosome among great apes. This means that the Y chromosomes of two healthy people can look very different. For example, one person may have 40 copies of a single gene while another person has 19. This development can now be studied better. In addition, it is now also possible to track genes across generations and see how the location and content of genes change over time. Finally, it is also now possible to study specific and unique Y chromosome sequencing patterns. Even within the Y chromosome, genes are divided into different regions, which differ widely in content, structure, and evolutionary history. Researchers are very interested in the extent of these changes on the Y chromosome and exactly how to explain them. With the help of new technologies, these questions can now be investigated more thoroughly.
More specifically, deciphering the entire Y chromosome provides more knowledge about the role the chromosome plays in the development of cancer. Genes on the Y chromosome are known to contribute to important aspects of human biology, such as cancer risk and severity. Researchers have previously discovered, for example, that male Y chromosomes can sometimes suddenly disappear from blood cells. This can then lead to an aggressive cancer. Thanks to the new sequence of the male sex chromosome, researchers can better study these diseases caused by genes.
In short, although there are relatively few genes on the Y chromosome, the genes that do exist are complex, dynamic, and encode important functions. A full reference to the Y chromosome will allow scientists to better study many features of this part of the human genome in a way that was not possible before. “We can now identify and study many genetic variations that can influence human traits and diseases,” says researcher Dylan Taylor.
all in all the findings Big step forward. “Until recently, we had an incomplete picture,” says researcher Rajeev McCoy. “But now, for the first time, we can see the entire genome from start to finish.” Not only does this provide more insight into basic biology, but it may also be a precursor to many genetic studies on different human diseases.
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