Mission accomplished

20 years ago, with the conclusion of the Genome Project, science achieved an amazing goal: after over 10 years of work, the first sequence of the human genome was published. Each of us has a genetic makeup of 3.2 billion nucleotides. Nucleotides are 4 different "bricks", which for simplicity we can indicate with the 4 initial letters A-T-G-C; the succession of the 4 letters determines the uniqueness of each of us. Due to the technology available at that time it had not yet been possible to have a 100% complete sequence; in fact, some regions equal to approximately 8% of the genome were missing. Despite this limitation, even then these data represented a Copernican revolution for biology and medicine, providing very important information for identifying regions responsible for genetic diseases.

20 years after this milestone, an international group of over 100 scientists from the T2T consortium completed the sequencing of the genome, reaching 100% complete readability. T2T is the abbreviation of Telomere-to-Telomere, which means “from telomere to telomere”, that is, from the beginning to the end of the chromosome. Approximately 200 million bricks not sequenced in previous versions have been revealed and some errors from previous readings have also been corrected.

Some thought that these missing bricks were unimportant, almost useless "garbage" in our genome, because they were not linked to the coding of proteins necessary for the functioning of our organism. In reality these gray areas are connected to regions with important cellular functions, such as cell division or genome aging. New sequencing technologies and the possibility of processing data with advanced computer systems have allowed reading accuracy unthinkable in the past and have given the possibility of reading repetitive pieces of DNA that had long defied research.
Is the work complete? In science we never reach the final goal, but every goal achieved opens up new possibilities. Future work will be to use this new material available to better understand the genetic basis of many diseases, correct genetic defects, diagnose susceptibility to certain pathologies early and allow personalized therapies.

Furthermore, we can try to understand the meaning of many repeated sequences, which can probably tell us something about our evolution.
In the past it was hypothesized that the complexity of man resided in the high number of genes, but already with the Genome Project it was understood that the evolution of man is based not so much on a very high number of genes, but on the possibility of regulating them in a much more sophisticated way than simpler organisms. Having the entire genome sequence available will allow us to better understand these evolutionary aspects.

Ultimately, sequencing work will advance to new heights: Science will work to define a reference human “pangenome,” based on the complete genome sequences of hundreds of individuals, with the goal of creating a complete human genome that represents much more human diversity and its infinite genetic facets.

Valentina Turinetto
NP August / September 2023