UMD Biologist Contributes to 2022 Nobel Prize in Medicine Research

Research by a Swedish scientist who won the 2022 Nobel Prize in medicine for his work on human evolution, including sequencing the Neanderthal genome, has links of its own to the University of Maryland.

Svante Pääbo’s studies using ancient DNA included collaborations from 2006 to 2014 with Philip Johnson, a UMD assistant professor of biology, and gave rise to the field of palaeogenomics and his discovery of a previously unknown hominin, Denisova. The work has expanded our understanding of what differentiates Homo sapiens from our extinct predecessors.

“What makes a human a human? That’s the core question that is at the heart of Svante’s work,” Johnson said. “The relationship between our evolutionary history and our current selves may not be obvious at first, but it’s definitely an important part of understanding who we are.”

Out of the six key publications the Nobel Prize Committee cited in justification for Pääbo’s prize, three were co-authored by Johnson. His work with Pääbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology in Germany, began when Johnson was a biophysics Ph.D. candidate at the University of California, Berkeley, at a time when ancient DNA research was still in its infancy.

“It was really driven by Svante and his work. He really gave the field a big push forward,” Johnson recalled. “In the early days, there was significant skepticism about its viability. My task was to help address those concerns.”

According to Johnson, a key problem was being able to demonstrate the authenticity of 400,000-year-old DNA samples.

“If you were interested in human evolution, you’d be digging up bones of beings that are very closely related to modern humans,” Johnson said. “One major worry about this type of research was how you would know if the small bits of DNA that you’re finding are really from the endogenous sample rather than contaminants from the modern humans who’ve come into contact with the sample—the archaeologists, the people at the museum who handled the bones or people in the laboratory. You touch something, a bit of your skin flakes off and you’re shedding DNA. That amount of DNA is comparable to the amount of degrading DNA remaining in the bone after thousands of years.”

To prove that the archaic DNA samples and analysis results were not compromised, Pääbo collaborated with the research group led by Johnson’s Ph.D. adviser, Montgomery Slatkin. The group’s expertise on theoretical population genetics—the study of genetic diversity and how that diversity changes over evolutionary time scales—was invaluable to Pääbo's search for ways to validate his findings.

Together with a student in Pääbo’s research group, Johnson helped build a crucial model describing the pattern of damage from DNA degradation and how it occurred with aging DNA. Johnson’s background in biocomputation and statistical modeling also helped him contribute to the development of additional techniques allowing researchers to infer levels of contamination from studying the frequencies of different genetic variants in the data.

“For me, the most fascinating part of all Svante’s research was confirming that there was interbreeding between fully modern humans and ancient hominids like Denisovans and Neanderthals,” Johnson said. “Mixture with Neanderthals had been hypothesized for a long time by anthropologists, but we couldn’t verify that until we had all the genetic data. And we actually didn’t know Denisovans existed until genetic evidence from Svante’s work. So, we weren’t just seeing a little bit of contamination that looked like interbreeding, but actual proof that there was interbreeding.”

Although Johnson’s work on ancient DNA was separate from his dissertation research, it helped shape the research in evolution he has conducted since.

“My funding was coming from grants and fellowships unrelated to ancient DNA and human evolution, so this was my personal interest and passion to pursue—a really fun side project for me that I wasn’t paid for,” Johnson joked.

Full of praises for Pääbo’s achievement, Johnson also noted that it was an unexpected victory for all scientists studying evolution because Pääbo won the prize in medicine. Johnson hopes that the Nobel Prize will encourage more research into ancient DNA and its connections and potential applications to modern humans.