A group of Johns Hopkins University scientists collaborated with more than 100 researchers around the world to assemble and analyze the first complete sequence of a human genome, two decades after the Human Genome Project produced the first draft. 

The work is part of the Telomere to Telomere (T2T) consortium. It’s led by researchers at the National Human Genome Research Institute (NHGRI); University of California, Santa Cruz; and University of Washington, Seattle. 

Johns Hopkins contributed key research to the effort to decipher our DNA—which has remained a mystery despite the initial progress 20 years ago. The revelations are expected to open new lines of molecular and genetic exploration while providing scientists with a clearer picture of how DNA affects the risks of diseases, and how genes are expressed and regulated. 

A package of six papers reporting the achievement appears in the March 31 issue of Science, along with companion papers in several other journals. 

The impact of the genome

Opening up these new parts of the genome, we think there will be genetic variation contributing to many different traits and disease risk.”

—Rajiv McCoy, assistant professor

Rajiv McCoy is assistant professor in the Department of Biology, whose research focuses on human genetics and evolution. “There’s an aspect of this that’s like, we don’t know yet what we don’t know.” 

McCoy and 12 Johns Hopkins researchers worked on different aspects of the international initiative. They contributed to the main genome assembly project and to several companion works analyzing what can be learned about patterns of genetic and epigenetic variation from person to person through the newly sequenced sections of the genome. 

The study found that because the previous model, known as the reference genome, was a composite of multiple individuals’ genomes essentially “stitched together,” it created artificial “seams” where the model switches from the genome of one person to another. The new, complete version eliminates those seams and is more representative of what an individual’s actual genome looks like. 

Using the new human genome model, the Johns Hopkins contributors also quantified how frequently different versions of the same gene occur in diverse human populations. That serves as an evolutionary record of both random fluctuations and potential natural selection affecting certain parts of the genome. 

Adapting to the new genome mapping

One immediate challenge McCoy identified is that clinical labs will need to transition from the previous genome mapping to the new complete version, no small undertaking, requiring that they adjust the information they have about the links between genes and diseases. 

“There are all sorts of databases and resources that have been built around the previous version, and it can be hard to get people to shift over,” he said. “So one goal of our work now is to encourage these important resources to move over to the new mapping to really empower the community.” 

Brian Welch, a PhD candidate in the Department of Physics and Astronomy, discovered a new star—the farthest star ever observed. The discovery paves the way for a new means to study the distant universe. 

The star, Earendel, is one of millions of stars observed in data collected from the Hubble Space Telescope’s Reionization Lensing Cluster Survey program. Welch’s research focuses on distant galaxies using gravitational lensing, where massive foreground objects distort and magnify the light from background objects—a process that was pivotal to the Earendel discovery. 

The find is a huge leap further back in time from the previous single-star record holder, detected by Hubble in 2018. That star existed when the universe was about 4 billion years old, or 30% of its current age, at a time that astronomers refer to as “redshift 1.5.” Scientists use the word “redshift” because as the universe expands, light from distant objects is stretched or “shifted” to longer, redder wavelengths as it travels toward us. 

12.9 billion years away

The newly detected star is so far away that its light has taken 12.9 billion years to reach Earth, appearing to us as it did when the universe was only 7% of its current age, at redshift 6.2. The smallest objects previously seen at such a great distance are clusters of stars embedded inside early galaxies. 

“We almost didn’t believe it at first; it was so much farther than the previous most-distant, highest redshift star,” Welch says. He is lead author of the paper describing the discovery, published in the March 30 journal Nature with co-author Dan Coe at the Space Telescope Science Institute in Baltimore. 

Because Welch made the discovery, he had the chance to choose the star’s nickname. He thought Earendel, an Old English word meaning “morning star,” was fitting, as he says the star is seen during the era often referred to as the cosmic dawn. 

The star nicknamed Earendel (indicated with arrow) is positioned along a ripple in spacetime that gives it extreme magnification, allowing it to emerge into view from its host galaxy, which appears as a red smear across the sky.