By reading the 8% that was missing
Scientists from the US and other countries have published the first complete and empty human genome, now covering all chromosomes from one end to the other with unprecedented precision.
Thus, after about 20 years, the project started with the Human Genome Program was completed, which by 2003 had “mapped” about 92% of the human genome. The remaining 8%, which had never been decoded and is now “read”, contains several genes and regions of repeating DNA, and is comparable in size to a chromosome.
The complete genome adds nearly 200 million base pairs of new DNA sequences, including 99 genes that probably encode proteins and nearly 2,000 candidate genes that need further study. It also corrects thousands of errors in the hitherto incomplete human reference genome (the so-called GRCh38), first introduced in 2000, assembled by multiple donors and not a single human, as is the case with the new complete genome.
More than 100 researchers from the US National Human Genome Research Institute (NHGRI) and several US and other universities, who had set up the T2T (Telomere to Telomere) science consortium, have published six more in other scientific journals.
They stressed that the existence of a complete sequence of a total of about three billion bases (“letters”) of human DNA is crucial to understanding the full spectrum of human genomic diversity, the genetic background of certain diseases and human evolution.
“Creating a truly complete sequence of the human genome represents an incredible scientific achievement, providing the first complete picture of our DNA background,” said NHGRI Director Dr. Eric Green.
“There are no more hidden or unknown parts of the human DNA. Psychologically, that alone is important,” said Robert Waterson, a geologist at the University of Washington.
“It’s a fundamental advantage to look at the complete genome to a complete system. It now allows us to shed light on how that system works. We had a huge understanding of human biology and disease having read about 90% of the human genome, but there were many important aspects.” hidden in the scientific darkness because we did not have the technology to read these parts of the genome.We can now stand on top of the mountain and see the whole landscape below and thus have a comprehensive picture of the human genetic heritage “, said David Hausler, director of the Institute of Genomics at the University of California-Santa Cruz.
Decoding the complete reference genome called T2T-CHM13 will facilitate a better understanding of how DNA differs from human to human. Already, using the complete genome as a reference point, researchers have discovered more than 2 million additional variants in the human genome, and more will surely follow in the future.
Completion of the genome reading was achieved at a lower cost than that of the original Human Genome Project ($ 3 billion), thanks to advances in DNA sequencing technology, particularly Oxford Nanopore Technologies.
The human genome is made up of billions of individual DNA “letters” divided into 23 chromosome pairs. To read the entire genome, scientists had to cut it into pieces of hundreds or thousands of letters each. The sequencing machines then read the individual letters (bases) in each piece and the scientists tried to assemble the pieces in the correct order, as in a difficult puzzle.
One difficulty is that some areas of the genome repeat the same letters over and over again. It used to be assumed that it was unnecessary “garbage”, but more recently it was realized that in these recurring not at all useless areas there are even new genes.
Another difficulty is that most human cells contain two genomes, one from the father and one from the mother. When scientists try to assemble all the pieces, the genetic sequences from each parent can be shuffled, blurring the true diversity in each individual genome. Finally, the researchers simplified their work by analyzing cells with a single genome (each such cell contained two copies of the father’s DNA and none of the mother’s).
The next step that consortium researchers are already working on is to sequence a genome with different chromosomes inherited from both parents. They also launched a pan-genomic effort (Human Pangenome Project) to read the complete DNA sequences of 350 people around the world, with the goal of creating as complete a human genome as possible, representing human diversity.