Nobel Prize in Physiology or Medicine 2022: Ancient Genomes and Human Evolution

This note covers the Nobel Prize in Physiology or Medicine 2022: who won it, how Svante Pääbo learned to read DNA from tens-of-thousands-of-years-old bones, how he sequenced the Neanderthal genome and discovered a brand new human relative called Denisova, how the discovery unfolded over his career, why it matters for understanding human evolution and disease, and quick facts for exams.

What was the Nobel Prize in Physiology or Medicine 2022 awarded for?

The Nobel Assembly at Karolinska Institutet gave the 2022 prize to a single scientist, with the citation: "for his discoveries concerning the genomes of extinct hominins and human evolution".

In plain words, the laureate found a way to extract and read the DNA (the chemical code that carries genetic information) preserved inside very old bones, some tens of thousands of years old.

Using this DNA, he reconstructed the complete genome (the full set of genetic instructions) of the Neanderthals, an extinct human-like species, and then discovered a second, previously unknown extinct group called the Denisovans.

He also showed that these extinct groups had interbred with our own species, Homo sapiens, leaving small traces of their DNA inside people alive today.

The prize's official name is the Nobel Prize in Physiology or Medicine, and it is chosen each year by the Nobel Assembly, which is made up of 50 professors at Karolinska Institutet in Sweden.

Who is the laureate?

Svante Pääbo

Svante Pääbo was born on 20 April 1955 in Stockholm, Sweden. At the time of the award he was affiliated with the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, with Leipzig University, and with the Okinawa Institute of Science and Technology in Japan. He received the entire prize himself, a prize share of 1/1.

Pääbo defended his PhD at Uppsala University in 1986 and later worked as a postdoctoral fellow at the University of Zürich, then at the University of California, Berkeley, in the laboratory of Allan Wilson, a pioneer of evolutionary biology.

He became a professor at the University of Munich in 1990, and and in 1999 he set up the Max Planck Institute for Evolutionary Anthropology in Leipzig, where he continued to work.

His central contribution was developing rigorous methods to retrieve and analyse ancient DNA from fossil bone, which let him sequence the Neanderthal genome, discover the Denisovans, and show that both groups had passed genes into present-day humans.

Why did scientists need to study the DNA of extinct human relatives?

Humans have long asked where they came from and how they are related to earlier human-like groups.

For most of the twentieth century, this question could only be studied through palaeontology (the study of fossils) and archaeology (the study of ancient tools and artefacts), by looking at the shape of bones and the objects found alongside them.

Fossil evidence showed that anatomically modern humans, Homo sapiens, first appeared in Africa around 300,000 years ago.

The Neanderthals, our closest known extinct relatives, developed outside Africa and lived across Europe and western Asia from roughly 400,000 years ago until they went extinct about 30,000 years ago.

Around 70,000 years ago, groups of Homo sapiens migrated out of Africa into the Middle East and then spread across the rest of the world, so for tens of thousands of years Homo sapiens and Neanderthals shared the same landscapes in Eurasia.

What remained unclear was whether the two groups ever interbred, and how closely related they really were.

By the close of the 1990s, researchers had sequenced almost the whole human genome, letting them compare living human populations with each other.

But answering the Neanderthal question needed something much harder: DNA taken directly from an extinct species' own bones, which by then had been degrading in the ground for tens of thousands of years.

How did Pääbo learn to read DNA from ancient bone?

DNA inside a living cell is stored in two places: the nuclear genome, which holds most of the genetic information but exists in only two copies per cell, and the much smaller mitochondrial genome, found inside structures called mitochondria, which exists in thousands of copies per cell.

After an organism dies, its DNA breaks down chemically over time, so that after thousands of years only tiny, damaged fragments remain, heavily contaminated with DNA from bacteria and from any present-day humans who later handled the bone.

Draw a cell with a large circle labelled "nuclear DNA" and several small circles labelled "mitochondrial DNA" inside mitochondria.

Then draw an hourglass next to a bone, showing the DNA strand breaking into short, damaged pieces and becoming mixed with bacterial and modern human DNA over time.

As a postdoctoral researcher with Allan Wilson, Pääbo began developing methods to extract and study DNA from Neanderthal remains, an effort that stretched across several decades.

Because mitochondrial DNA exists in far more copies per cell than nuclear DNA, it gave a far better chance of recovering any surviving genetic material, so Pääbo targeted it first.

In 1990, now a professor at the University of Munich, Pääbo refined his techniques enough to sequence a short stretch of mitochondrial DNA from a 40,000-year-old Neanderthal bone fragment.

Comparing this sequence with those of present-day humans and chimpanzees showed that Neanderthals were genetically distinct from both, giving scientists their first direct genetic window into an extinct relative.

The broad method Pääbo built up, step by step, over his career looked roughly like this:

1. Select a bone or tooth fragment and test it chemically for signs that enough original DNA might still survive.
2. Work inside specially designed clean rooms to minimise contamination from bacteria and from the researchers' own DNA.
3. Extract the fragmented DNA using purification methods, then build it into readable DNA libraries.
4. Use high-throughput sequencing machines to read millions of short DNA fragments at once.
5. Compare the sequences against reference genomes from present-day humans and chimpanzees, and have independent laboratories repeat the experiment to confirm the results.

How did Pääbo sequence the Neanderthal genome and discover the Denisovans?

Studying the small mitochondrial genome alone gave only a limited picture, so Pääbo set out on the far harder task of sequencing the much larger nuclear genome of the Neanderthal.

After he was offered the chance to establish a new Max Planck Institute in Leipzig, his team steadily improved their methods and took advantage of new, highly efficient sequencing technology, while also bringing in collaborators skilled in population genetics.

In 2010, Pääbo's team published the first draft sequence of the Neanderthal genome, a result once thought almost impossible to achieve.

Comparing this genome with sequences from people around the world produced a striking finding: Neanderthal DNA was more similar to the DNA of present-day Europeans and Asians than to that of present-day Africans.

The simplest explanation was that Neanderthals and Homo sapiens had interbred while they coexisted outside Africa. Today, people of European or Asian descent carry roughly 1 to 4% Neanderthal DNA in their genomes.

Then, in 2008, a tiny 40,000-year-old finger bone fragment was found in the Denisova Cave in southern Siberia.

Its DNA was unusually well preserved, and when Pääbo's team sequenced it, the sequence did not match any known Neanderthal or present-day human DNA. Pääbo had discovered an entirely new, previously unknown hominin, which was named Denisova.

Comparisons with living populations showed that this group had also interbred with Homo sapiens, particularly with the ancestors of people in Melanesia and other parts of south-east Asia, who carry up to about 6% Denisovan DNA.

Draw a branching tree with a shared ancestor at the base splitting into three lines labelled Homo sapiens, Neanderthal and Denisovan, with short crossing arrows between the branches where the lines overlap in time, showing interbreeding.

Pääbo's work showed that at the time Homo sapiens expanded out of Africa, Neanderthals lived mainly in western Eurasia while Denisovans occupied the eastern parts of the continent, and that early modern humans mixed with both groups as they spread across these regions.

What did these ancient genomes reveal about human evolution and health?

Pääbo's discoveries created an entirely new field of science, which the Nobel Committee's press release named paleogenomics, the study of genomes recovered from ancient or extinct organisms. This field now gives researchers a genetic reference point for exploring exactly what distinguishes living humans from our closest extinct relatives.

The gene flow between extinct hominins and Homo sapiens left behind genetic variants that still affect people today.

One well documented example is a version of the gene EPAS1, inherited from Denisovans, which helps the body cope with low oxygen levels at high altitude and is common among present-day Tibetans.

Other inherited Neanderthal gene variants influence how the human immune system reacts to infections.

Homo sapiens and Neanderthals were similar in many ways: both lived in groups, had large brains and used tools.

Yet Neanderthal tools changed very little over hundreds of thousands of years, while Homo sapiens went on to develop complex cultures, figurative art, advanced tools and the ability to cross open water and settle across the entire planet.

The genetic differences that Pääbo identified between extinct hominins and living humans provide a starting point for research into what makes our species biologically distinctive, although the full answer to that question is still being worked out.

How did the discovery unfold?

Svante Pääbo's path to the 2022 Nobel Prize stretched across more than three decades, beginning with early experiments on ancient DNA and ending with the sequencing of two extinct hominin genomes. The timeline below traces the main public milestones in that long journey, from his first professorship studying archaic bone to the announcement of the prize itself.

Across these years, Pääbo's team repeatedly had to rebuild its laboratory methods as new sequencing technologies became available, always testing results against independent replication to guard against contamination from bacteria or present-day humans. This steady accumulation of better-preserved bone samples, cleaner clean-room protocols, and faster sequencing machines was what eventually turned a task once thought impossible into two landmark genome sequences and an entirely new scientific field.

Why does it matter?

Pääbo's methods proved that genetic material can survive, in trace amounts, for tens of thousands of years, and that it can be reliably read despite heavy contamination and chemical damage.

This opened the door to studying many other ancient genomes, not just from Neanderthals and Denisovans but also from ancient Homo sapiens remains, giving scientists an unprecedented view of how humans moved and mixed across the planet.

The discoveries also matter for medicine today. Archaic gene variants inherited from Neanderthals and Denisovans continue to shape human physiology, including how strongly the immune system reacts to certain infections and how well the body copes with low-oxygen environments.

Research into these inherited variants is an active area of study, and no genome from an extinct hominin in Africa has yet been sequenced, because hot, humid conditions there make ancient DNA degrade far faster than in cooler regions such as Siberia.

This leaves open questions about how archaic hominins in Africa may also have mixed with early Homo sapiens.

How does this connect to what you study?

Pääbo's work connects directly to school topics in genetics and evolution: how DNA carries hereditary information from parents to offspring, how small changes called mutations build up in a population's DNA over long stretches of time, and how gene flow between separate populations, known as introgression, can mix their genetic material even after the populations have evolved apart for hundreds of thousands of years.

It also connects to the idea of a phylogenetic tree, the branching diagram biology students use to show how species or populations are related to one another, since Pääbo's genome comparisons let scientists estimate roughly when Neanderthals, Denisovans, and Homo sapiens last shared a common ancestor.

Finally, the story shows how a demanding technical skill, extracting usable DNA from bone that is fragmented, chemically damaged, and heavily contaminated, can open up an entirely new area of biological research once the right laboratory methods are developed and carefully checked by independent teams working in different laboratories.

Quick facts for exams

The Nobel Prize in Physiology or Medicine 2022 was awarded in full to Svante Pääbo, a Swedish scientist based at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, "for his discoveries concerning the genomes of extinct hominins and human evolution".

The award was announced on 3 October 2022 by the Nobel Assembly at Karolinska Institutet, and the prize carried a value of 10,000,000 Swedish kronor.

Pääbo sequenced the Neanderthal genome and discovered a previously unknown extinct relative, the Denisovan, showing that both groups had interbred with Homo sapiens, leaving traces of archaic DNA in people living today.

Note: Source. The prize facts in this note are from the Nobel Prize's official site, nobelprize.org.

Glossary

• DNA — the chemical molecule inside cells that carries genetic instructions, passed from parents to offspring.
• Genome — the complete set of genetic instructions of an organism.
• Nuclear genome — the large set of DNA stored in a cell's nucleus, present in two copies per cell.
• Mitochondrial genome — the small DNA set inside mitochondria, present in thousands of copies per cell.
• Hominin — a human or a close extinct relative of humans, such as a Neanderthal or Denisovan.
• Neanderthal — an extinct hominin species that lived across Europe and western Asia from about 400,000 to 30,000 years ago.
• Denisovan — an extinct hominin group, first identified from a finger bone found in Siberia, distinct from Neanderthals.
• Paleogenomics — the scientific field, founded through Pääbo's work, that studies genomes recovered from ancient or extinct organisms.
• Interbreeding — reproduction between members of different populations or species, which can mix their genetic material.
• Gene flow (introgression) — the transfer of genetic material from one population or species into another through interbreeding.
• Contamination (in ancient DNA) — unwanted DNA from bacteria or from present-day humans mixed in with an ancient sample.
• EPAS1 — a gene, with a Denisovan-derived version in Tibetans, that helps the body handle low oxygen at high altitude.
• High-throughput sequencing — technology that reads very large numbers of DNA fragments at once, speeding up genome analysis.

Common errors and misconceptions

• Misconception: Neanderthals are the ancestors of modern humans. Correct: Neanderthals and Homo sapiens shared a common ancestor and later interbred, but Neanderthals are a separate, extinct lineage, not a direct ancestor of present-day humans.
• Misconception: Pääbo discovered the Denisovans by finding a complete skeleton. Correct: The entire Denisovan group was identified from DNA extracted from a single small finger bone fragment.
• Misconception: All present-day humans carry the same amount of Neanderthal DNA. Correct: Only people of non-African descent carry roughly 1 to 4% Neanderthal DNA, reflecting where interbreeding occurred.
• Misconception: Ancient DNA can be read exactly like fresh DNA from a living person. Correct: Ancient DNA is fragmented, chemically damaged and heavily contaminated, so it needs special clean-room extraction and careful verification.
• Misconception: The prize was shared between several scientists who worked on ancient DNA. Correct: The 2022 prize was awarded entirely to Svante Pääbo alone, a prize share of 1/1.
• Misconception: Denisovan DNA is found equally in all human populations. Correct: Denisovan DNA is found at much higher levels in Melanesian and south-east Asian populations than elsewhere.

Exam-style questions with model answers

Q1. In which year was the Nobel Prize in Physiology or Medicine 2022 announced, and by which body? [1 mark]

1. The prize was announced on 3 October 2022 by the Nobel Assembly at Karolinska Institutet, which is made up of fifty professors responsible for choosing the physiology or medicine laureate each year.

Q2. State the official citation for the 2022 Nobel Prize in Physiology or Medicine, and name the laureate it was awarded to. [2 marks]

1. The 2022 Nobel Prize in Physiology or Medicine was awarded to Svante Pääbo with the citation "for his discoveries concerning the genomes of extinct hominins and human evolution".

Q3. Explain why mitochondrial DNA was Svante Pääbo's first target when studying Neanderthal remains. [4 marks]

1. Mitochondrial DNA exists in thousands of copies inside each cell, while nuclear DNA exists in only two copies, so mitochondrial DNA has a much greater chance of surviving in small, degraded amounts after thousands of years.
2. Pääbo used this advantage to sequence a short stretch of Neanderthal mitochondrial DNA from a 40,000-year-old bone in 1990, comparing it with present-day humans and chimpanzees to show that Neanderthals were genetically distinct.

Q4. Describe how Svante Pääbo discovered the Denisovans. [4 marks]

1. In 2008, a tiny, 40,000-year-old finger bone fragment was found in the Denisova Cave in southern Siberia.
2. The bone contained exceptionally well-preserved DNA, which Pääbo's team sequenced.
3. The resulting sequence did not match any known Neanderthal or present-day human DNA, revealing a previously unknown hominin.
4. This new group was named Denisova, and further comparisons showed it had interbred with the ancestors of present-day Melanesians.

Q5. Discuss the main scientific and medical significance of Svante Pääbo's discoveries. [6 marks]

1. Pääbo developed methods to extract and reliably sequence DNA from bones tens of thousands of years old, overcoming severe degradation and contamination, and in doing so created the new field of paleogenomics.
2. He produced the first draft genome of the Neanderthal in 2010 and discovered an entirely new extinct hominin group, the Denisovans, from a single finger bone.
3. His comparisons showed that Neanderthals and Denisovans had interbred with Homo sapiens as modern humans spread out of Africa, so people today carry small amounts of archaic DNA, roughly 1 to 4% Neanderthal DNA in non-Africans and up to about 6% Denisovan DNA in Melanesians.
4. These inherited gene variants have physiological effects today, such as the Denisovan-derived EPAS1 variant helping Tibetans cope with high altitude, and Neanderthal-derived variants influencing immune responses to infection.
5. His work also gives researchers genetic reference points for investigating what distinguishes modern humans biologically from our closest extinct relatives, an area of research that remains active.

Q6. Why has no genome from an extinct hominin in Africa been sequenced yet? [2 marks]

1. Hot, humid conditions in Africa cause ancient DNA to degrade much faster than in cooler regions such as Siberia, so no usable archaic hominin genome from Africa has been recovered so far.

Q7. Where was Svante Pääbo affiliated at the time of the award, and what institute did he found? [3 marks]

1. At the time of the award, Pääbo was affiliated with the Max Planck Institute for Evolutionary Anthropology and Leipzig University in Germany, and with the Okinawa Institute of Science and Technology in Japan.
2. He himself set up the Max Planck Institute for Evolutionary Anthropology in Leipzig in 1999.

Key takeaways

• Svante Pääbo won the Nobel Prize in Physiology or Medicine 2022 alone, for discoveries about extinct hominin genomes and human evolution.
• He developed clean-room methods to extract and sequence DNA from bones tens of thousands of years old.
• In 2010, his team published the first draft genome of the Neanderthal, a feat once seen as nearly impossible.
• In 2008 to 2010, Pääbo discovered an entirely new extinct hominin, the Denisovan, from a single finger bone.
• Neanderthals and Denisovans interbred with Homo sapiens, leaving archaic DNA in people living today.
• Inherited variants, such as the Denisovan EPAS1 gene in Tibetans, still affect human physiology.
• Pääbo's work founded the new field of paleogenomics, the study of ancient genomes.
• Degradation in hot, humid climates means no African extinct hominin genome has yet been sequenced.

Test yourself

What species did Svante Pääbo sequence the genome of in 2010?

Svante Pääbo's team published the first draft genome sequence of the Neanderthal in 2010.

What previously unknown hominin did Pääbo discover from a finger bone?

Pääbo discovered the Denisovan, a previously unknown extinct hominin, from a tiny finger bone found in Siberia.

Roughly how much Neanderthal DNA do present-day Europeans and Asians carry?

Present-day people of European or Asian descent carry roughly 1 to 4% Neanderthal DNA in their genomes.

Which gene inherited from Denisovans helps Tibetans survive at high altitude?

The gene EPAS1, in its Denisovan-derived version, helps present-day Tibetans cope with low oxygen at high altitude.

Where is the Max Planck Institute for Evolutionary Anthropology, which Pääbo founded?

Svante Pääbo founded and worked at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

What new scientific field did Pääbo's discoveries create?

Pääbo's discoveries created the new scientific field of paleogenomics, the study of genomes from ancient or extinct organisms.

Why has no extinct hominin genome from Africa been sequenced yet?

Hot, humid African conditions degrade ancient DNA faster than cooler regions, so no African extinct hominin genome has been recovered so far.