Scientists have finished mapping the entire human genome, about 20 years after most of the map was complete. In new research this week, a team reports they have achieved a gapless genome sequence, accounting for 8% of genetic information not previously known. The missing data may provide more insights about the evolutionary journey of humans as well as our susceptibility to diseases.
In 2003, a large coalition of scientists at the Human Genome Project unveiled the fruits of their labor: a nearly complete rendering of our genetic code. Even back then, though, it was known that they hadn’t gotten everything. Due to limitations at the time, they had focused on translating and reconstructing DNA from the euchromatin regions of the genome—the chunks of DNA, RNA, and proteins that are less tightly packed and are often active in our cells. This still amounted to mapping 92% of the genome, but it meant that the DNA in our heterochromatin regions would go undiscovered for some time.
Heterochromatin has been referred to as the dark matter of our genetic structure. Its chunks of genetic material are densely packed and filled with repeated sequences of DNA, both of which have made it harder to translate and reconstruct into something readable. But over the years, advances in genetic sequencing and a few lucky breaks have allowed scientists to get closer to deciphering these gaps. That eventually led researchers at the Telomere to Telomere (T2T) consortium to commit to fully mapping the genome. One of these breaks involved finding a cell line derived from those with a rare condition that left their cells with two identical copies of their father’s genome, as opposed to both parents like usual (the mixing of two genomes can make translating harder).
Even with machines now able to sequence DNA faster than ever before with near perfect accuracy, the effort still required manual translation for the most complex bits. But by 2020, the large team of scientists had published research on the first chromosomes they had mapped. By May 2021, they felt confident enough to release a preprint of their work on the entire genome. And in a new paper published Thursday in the journal Science, their full peer-reviewed work has finally been unveiled.
According to study author Evan Eichler, a researcher at the University of Washington School of Medicine and co-chair of the T2T consortium, the findings should provide valuable new insights about many different aspects of our biology and history. In time, he added, what we learn from this could very well revolutionize our current thinking about the variations inherent in our genes and how they have affected our evolutionary journey, along with the health problems that can arise from mutations.
Though the repeated bits of DNA found in our heterochromatin were once considered to be little more than junk, we now know that they fill a vital role. In humans and other mammals, for instance, this DNA is thought to help structure the genome as a whole, which includes silencing other genes that could be harmful. Heterochromatin DNA is also abundantly found in our centromeres, structures in our chromosomes that help ensure that chromosomes end up where they belong when cells divide.
“We are getting complete information for the equivalent of one entire chromosome,” Eichler told Gizmodo in an email. “These include regions important for segregation of chromosomes (centromeres), genes important for the production of proteins (rDNA genes), and duplicate genes important for making us human (i.e. the building of a bigger brain), for immunity and drug detoxification among others.”
And by simply having a full reference map available, the authors say, we can better find and track variations in our DNA that could tell us something about genetically influenced health conditions—work that the team is already doing.
“The complete human genome is making accessible for the first time hundreds of genes and parts of genes that we know are important to human health but were difficult to sequence and assay,” said Eicher. “As such, we will have more power to make genetic associations with disease and thereby make new discoveries.”
The team’s mapping efforts aren’t done yet, though. They next plan to sequence the genome of chromosomes that are mixed with both parents’ genes, as is typical. And eventually, they’d like to sequence people’s genes from across the world, in hopes of better understanding the full variation of our genetics.
“We’ll start with dozens and then hundreds and ultimately have thousands, so we will better represent the diversity of human genomes,” Eichler said.