Nobel Prizes and ancient DNA – an explainer

On 3 October the Nobel Committee announced that Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology would be awarded the 2022 Nobel Prize in Physiology or Medicine “for his discoveries concerning the genomes of extinct hominins and human evolution”. This marks the culmination of an illustrious career which began with the first sequence of human ancient DNA and continued with increasingly innovative studies, such as the publication of the Neanderthal and Denisovan genomes, revealing that we share around to 2 and 4-6 % of our DNA with these extinct hominins. These publications were later followed up with studies on the role of extinct hominin DNA in modern humans, showing, for example, a clear link between severe COVID-19 and a certain sequene of Neanderthal DNA present in around 50 % of south Asians and 16 % of Europeans.

Pääbo’s studies have not only changed our understanding of extinct human species and how they relate to us, they are also largely responsible for creating a novel field of scientific study known as palaeogenomics. This is an interdisciplinary field of study that looks at ancient DNA in order to trace the evolutionary and population history of humans, animals, plants, and microbes. It’s not entirely without its critics and shortfalls, however, and with the awarding of the Nobel Prize it’s more important than ever to understand exactly what it can and can’t tell us about the past.

Svante Pääbo received the Nobel Prize based in part on his work with ancient Neanderthal DNA. This work led to the publication of the first Neanderthal genome in 2010, revealed that modern non-Africans have about 2 % Neanderthal DNA within our own genomes, and shown a clear link between severe COVID-19 and certain parts of Neanderthal DNA present in modern humans. Image: Wikimedia Commons.

What is ancient DNA?

Every living organism contains DNA within its cell inherited from its ancestors. This is either mitochondrial or nuclear. Mitochondrial DNA is located within a specific part of your cells called mitochondria, and it’s inherited from entirely from your mother. Nuclear DNA is contained within the nucleus of your cells and is inherited from both of your parents. It makes up your twenty-three chromosome pairs which themselves make up your nuclear genome. Together with the mitochondrial genome, which consists of the entire genetic information contained within your mitochondria, the nuclear genome contains the entirety your genetic information and inheritance. Since DNA mutates at a largely constant rate, it’s possible for researchers to compare the genomes of different organisms to infer their relatedness back in time.

Consequently, it’s been possible to establish that humans originated in Africa and that all non-Africans derive from a migration out of the continent beginning around 70,000 years ago. In theory, it’s possible to trace human ancestry back to the beginning of life 3.7 billion years ago. However, since this is based on assumptions about the rate at which DNA mutates, the margins of error become significantly larger the further back in time researchers go.

A second issue with modern DNA is that it not every organism that ever lived had ancestors. Extinct species, such as all hominins that predate our own species, Homo sapiens, are impossible to study through modern DNA.

All cells contain a nucleus within which all twenty-three chromosome pairs are located. These chromosomes are made up of DNA. Since DNA is inherited from your parents, it’s possible to use your DNA to trace your ancestry back in time – theoretically back to the beginning of life 3.7 billion years ago. Illustration: Wikimedia Commons.

Ancient DNA solves these issues since it provides DNA directly from ancient and extinct organisms. The Neanderthal genome published by Svante Pääbo and his colleagues in 2010, for example, was based on DNA extracted from 40,000 year old Neanderthal bones. This provided them with a direct window into the past. When compared with modern human genomes, the researchers were able to show that around 2 % of the DNA in modern humans derive directly from Neanderthals. Consequently, it’s clear that our own species and Neanderthals met and had children at the same time that we left Africa. Although some researchers already thought this was the case, it was not possible to prove without the direct evidence provided by ancient DNA.

Since DNA begins to degrade rapidly upon an organism’s death, there’s a limit to how far back in time researchers can go. At present, the oldest DNA sequence comes from mammoths that lived 1.3 million years ago in Siberia, and the oldest human DNA derives from 400,000 year old hominins that lived in Spain. Although it’s possible that even older DNA will be published in the future, DNA is completely degraded after a few million years. No matter how sophisticated our technology becomes, cloning dinosaurs from their DNA will remain within the realm of Hollywood blockbusters.

Although every living organism contains DNA it doesn’t mean that it’s possible to study any ancient creature. Dinosaurs, for example, are too ancient to be studied since DNA is completely degraded within only a few million years. Not even every human species that’s lived can be studied. Illustration: Public Domain.

During both life and death, humans, plants, and animals are hosts to a range of different microorganisms. Ancient DNA researchers therefore have to be careful that they analyse the DNA they’re interested in and not the DNA of colonising microorganisms. These microorganisms can be interesting in their own right, however. For example, they can be used to show which bacteria were present in an organism when it died and, consequently, whether it had certain diseases. This is how researchers showed that the infamous Black Death of the Middle Ages was due to plague and not the myriad other diseases that have been proposed.

Finally, we leave traces of DNA on everything that we come in contact with. This is part of how modern forensics are able to safely identify criminals based on a few physical clues. It’s also a major issue in ancient DNA research, as careless handling of bones, objects, or tissue can result in the researcher’s own DNA being sequenced rather than the DNA they’re actually interested in. This was the case when 65 million year old dinosaur DNA was published in the scientific journal Science which later turned out to be the researchers’ own human DNA.

Ancient DNA is extremely useful in allowing researchers to study the relationship between organisms in the past, including organisms that are extinct today. However, several technical pitfalls need to be kept in mind when consulting these studies since the studied DNA may turn out to be something entirely different than originally thought.

Ancient DNA as a tool for human history

Ancient DNA studies regularly make headlines as they reveal massive human migrations in the past. The potrayal of these massive migrations – although not their existence – has occasionally drawn the ire of archaeologists and historians who feel that the past risks being portrayed in an overly simplistic and problematic way.

The discussions about whether ancient DNA can be used for studying human (pre-)history has generated endless pages of technical jargon in scholarly journals. Some archaeologists, antropologists, and historians feel that genetic data is given greater weight than data derived from their methods, which risks producing skewed conclusions of the past. This is not least due to a lot of regional variety that is often left out by ancient DNA studies. Others argue that researchers too often fail to include stakeholders, such as indigenous communities, in the critical stages of the research. This is especially problematic since ancient DNA requires the destruction of the samples from which DNA is to be retrieved.

Inreasing care is being taken to secure the involvement of key stakeholders, including indigenous and local communities who’re directly impacted by the results of ancient DNA. And ethical guidelines are suggested in key journals, helping secure that all researchers follow minimal best-of-practices. Potentially, ethical requirements in high-impact journals such as Nature and Science can ensure that no community is harmed or aggrevated by ancient DNA research.

Kennewick Man is a 9,000 year old Native American skeleton whose ancestry was long controversial. According to some anthropologists, the skull exhibited features resembling Caucasians rather than Native Americans, and, consequently, some researchers argued that the skeleton wasn’t Native American at all. But a 2015 study of the skeleton’s DNA led by Eske Willerslev showed that it was in fact Native American. The results were corroborated independently by researchers at the University of Chicago. As a result, the skeleton was given back to descendant communities and buried in 2016. Image: Brittney Thatchell, Smithsonian Institute.

As for collaboration between ancient DNA and other researchers, progress is also being made. Archaeologists, historians, and anthropologists are increasingly getting to grips with the nature of the data produced by ancient DNA whereas genticists are increasingly realising that their data is just one of many different kinds of data that can illuminate the past. Only by collaborating can historians, archaeologists, anthropologists, and geneticists truly understand the deep complexity of the human past.

Although some are sure to ignore the novel insights provided by palaeogenomics, Svante Pääbo’s Nobel Prize clearly signifies that the field will only become more important in the future. It’s up to historians, archaeologists, and anthropologists to ensure direct, thoughtful collaboration with geneticists so that the past is continuously studied and presented in its full complexity and with the continued participation of local and indigenous communities. If this is done, ancient DNA can prove to be the most significant innovation in our understanding of the human past in decades.

Cover image: Svante Pääbo holding a Neanderthal skull, Max Planck Institute for Evolutionary Anthropology.

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