The complete human genome decoded for the first time

On June 26, 2000, the President of the United States Bill Clintonaccompanied by researchers J. Craig Venter And the Francis Collinsto announce to the world that The human genome project was a success: Most of the protein-coding genes, the “lines of code” that make us human, have been untangled. However, a small spot covered the teacher: A 8% of the genetic code, about 151 million sequences, have escaped scrutiny. received the derogatory nickname of ‘unwanted DNA‘: a redundant substance incapable of coding and abandoned by evolution in the bends of our chromosomes.

But for some researchers, it was like completing a puzzle and discovering that you had pieces left: these blind spots have been an obsession for the past two decades. about Evan Eichlera researcher at the Howard Hughes Medical Institute (HHMI) at the University of Washington, these scattered areas in The genome, consisting of long repetitive sequences with duplicated genes, was precisely the ‘most interesting’. Now, together with hundreds of scientists who make up Telomere to telomere union (T2T), you can claim victory: The sequencing of the human genome has been completedas published by the magazine to know.

“You might think that with 92% of the genome complete so long ago, the remaining 8% wouldn’t contribute much,” he says with humor. Eric D Jarvis, a researcher at Rockefeller University and co-author of the work. “But thanks to that part that was overlooked We understand cell division in a whole new wayIt will allow us to study different diseases that were previously inaccessible.” National Human Genome Research Institute (NHGRI) and the University of California (UC) are other centers that have contributed to the discovery.

As Eichler explains, the human genetic code consists of three billion base pairs (about six billion individual letters – the most famous of which is adenine (to), thymine (T), cytosine (Atmosphere guanine (G)-) More than 23 pairs of chromosomes are scattered. The Human Genome Project was able to ‘cut’ these lines of DNA into sequences hundreds to thousands of letters long, which the researchers rearranged again, like a book page ripping apart and pieced together letter by letter. This task was performed in real chromatin which make up 92% of the genome: a highly active region with relatively well-defined genes that produce RNA Necessary for the manufacture of proteins.

This was not possible in the remaining area, and heterochromatinbecause the letter sequence was Too long and repetitive that the scientists could not put them back together. Thus, the sections that were left blind included centromereThe union point From the chromosome separating it into a short arm and a long arm. When a cell divides, it does so part One It must be repeated correctly To ensure that the copy is free of defects. Despite its importance, it has remained a mystery until now. “We used to tell young geneticists not to go into the centromere because they wouldn’t get out,” jokes another researcher, who is a professor of evolution and ecology at the University of California. Charles Langley.

Today, technology enables the most comprehensive genetic sequencing: Project Technical Partners – Jarvis Labs, Oxford Nanopore Technologies, Biological Pacific- Provided tools to analyze long sequences with high accuracy and – Margin of success 99.9%., as well as algorithms capable of detecting anomalies and errors. However, the length of the lines was not the only difficulty to overcome. Most cells contain Genoman, one from the father and the other from the mother,” explains Eichler. When researchers try to piece the pieces together, sequences from each parent can Ultimate mixing‘, causing confusion.

The solution was to work with cells that retained one copy of the genome, due to some changes, but did not suffer from any other kind of abnormality. Thus, the reference genome does not belong to a “human being” in the strict sense of the word: it was obtained from a non-cancerous tumor named hydatidiform mole, which occurs when an egg loses its genetic material but is fertilized by a sperm. So it ends up containing Two identical copies of the same genome. The researchers point out that the amount of genes and material that appeared with this process is equivalent to “one more chromosome.”

“Treasure Chest of Variables”

The authors of the discovery do not spare the literary qualities. “We see Unread chapters appear before the Genetic Codex of Life‘, shines Eichler. Previously unexplored regions of the centromeres and TelomeresSequences at the ends of chromosomes reveal “unprecedented levels of human genetic variation in genes essential for neurodevelopment and related diseases”. Adam Felipeof the NHGRI, describes it as a “real treasure chest of genetic variants”.

“We know that many diseases are linked to structural repeats in the centromere, and now that these sequences are part of the reference human genome, we can begin to map the origins of these diseases,” Jarvis says. The cancer is the main line of research: The metastatic cells multiply uncontrollably when Some centromere heterozygous genes are overexpressedKnowing them completely could open the door to new treatments.

Centromere alterations are also associated with congenital disorders associated with defects in the replication ability of cells, such as Down’s syndrome. This technology also made it possible to fully analyze a file Y . chromosome It differs from the reference genome, because it is from African origin when the second European. The results are awaiting publication, but the genetic variation found in the male chromosome would be such that it “took too long to sequence” for the remaining human genome to be terminated.

Finally, the implications of the discovery for personalized medicine are relevant. “In the future, when someone goes to sequence their genome, we will be able to identify all the variants in their DNA and use that information to better guide healthcare.” Philippe. “Completing the sequencing of the human genome was like putting on a new pair of glasses. Now we can see everything clearly, and we’re one step closer to understanding what it really means.”

Follow the topics that interest you