Jacinta Bowler
DNA is no friend to time. As the millennia wear on, DNA degrades to a point that sequencing the genome is almost entirely impossible, but only by revealing genetic differences that distinguish all living humans from extinct hominins, can we provide the basis for exploring what makes us unique.
That is why the 2022 Nobel Prize in Physiology or Medicine has gone to Svante Pääbo – whose team published the first Neanderthal genome sequence in 2010 and has since pioneered genomic analysis into both Neanderthals and the mysterious ‘Denisovans’.
The researcher has been awarded the prize ‘for his discoveries concerning the genomes of extinct hominins and human evolution’ and his research gave rise to an entirely new scientific discipline – paleogenomics.
Paleogenomics
Our genes tell a story about our history. Where we’ve come from and who we’ve mingled with along the way.
But as biologist Eric Lander, who helped lead the effort to sequence the first human genome put it: “Genome: Bought the book; hard to read.” Ancient DNA has a different problem – the book is in tatters.
Because DNA degrades over time, being able to extract even limited information is difficult. In 1997 Pääbo made his first breakthrough by reconstructing the first mitochondrial DNA from a Neanderthal.
Mitochondria – known as the ‘powerhouse of the cell’ – has its own set of DNA which is passed down from the mother.
Because there’s so many mitochondria in each cell, this DNA – which is called mtDNA – is the most accessible, and easiest to sequence – especially in ancient, degraded cells.
Pääbo was conducting his work only seven years after the Human Genome Project had begun and six years before it would be even moderately completed – DNA sequencing was still in its relative infancy.
The researchers continued refining the mitochondrial DNA, and also began looking a step further – trying to sequence the nuclear DNA of a Neanderthal.
Neanderthal DNA
Pääbo and his team steadily improved the methods to isolate and analyse DNA from archaic bone remains. The research team exploited new technical developments, which made sequencing of DNA much more efficient. Pääbo also engaged several critical collaborators with expertise on population genetics and advanced sequence analyses.
In 2010 Pääbo’s team made a second major breakthrough – they published a paper with the first draft of the Neanderthal nuclear genome sequence. Imagine this as a carefully reconstructed book, some pages sticky taped back together, while others having to be brought in from elsewhere to fill the gaps.
Having this entire genome means that we can now work out how Neanderthals and humans are different. Comparative analyses demonstrated that the most recent common ancestor of Neanderthals and Homo sapiens lived around 800,000 years ago, while more recently we discovered that Neanderthals and humans likely interbred, meaning that most of us have a few percentage points of DNA from this cross over.
Denisovans
In 2008 a 40,000-year-old fragment from a finger bone was discovered in the Denisova cave in the southern part of Siberia. The bone contained exceptionally well-preserved DNA, which Pääbo’s team sequenced.
The results caused a sensation – the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans.
Pääbo and the team had discovered a previously unknown hominin, which was given the name Denisova. And, seemingly as these things go, comparisons with contemporary human genomes from different parts of the world showed that gene flow had also occurred between Denisova and Homo sapiens too.
“Pääbo’s discoveries have had a profound impact on the understanding of our evolutionary history, and they have galvanized research in the area,” wrote Gunilla Karlsson Hedestam and Anna Wedell, professors at the Karolinska Institute, in a background article about the prize.
“We now know that at least two distinct hominin groups, Neanderthals and Denisovans, inhabited Eurasia when anatomically modern humans (Homo sapiens) emerged from Africa.”
You can read more about Pääbo’s Nobel prize announcement here.