Prof. Rimantas Jankauskas: “Neanderthal DNA Still Benefits Our Immune System”

Paleogenetics is a field of science that studies the genetic material of ancient organisms. Research in this area is unique due to the highly stringent conditions required for conducting studies and presenting their findings. However, as methodologies advance, we can uncover more and more new insights. One of the greatest achievements in paleogenetics has significantly reshaped the theory of human origin as a biological species.

“In 2022, Swedish geneticist Svante Pääbo was awarded the Nobel Prize in Physiology or Medicine for his research on the Neanderthal genome. Traditionally, it was considered that human evolution followed a linear progression: Homo erectus, Neanderthals, and then modern humans. Subsequent studies showed that modern humans and Neanderthals are distinct and directly unrelated species. However, today, we have definitive evidence that they were, in fact, genetically related and even capable of producing viable and fertile offspring,” explained Prof. Rimantas Jankauskas from the Translational Health Research Institute at the Faculty of Medicine of Vilnius University (VU).

We spoke with Prof. Jankauskas about the challenges of paleogenomics, the most significant discoveries, and the soon-to-be-established Paleogenomics Laboratory at the VU Medical Science Centre.

Special laboratory conditions

According to Prof. Jankauskas, the best-preserved genetic material is found in cold environments. Genetic material from Siberian mammoths dates back up to a million years, while samples discovered in Greenland have survived for as long as two million years.

“In our region, conditions are somewhat different. Genetic material can typically be preserved for tens of thousands to 100,000 years, depending on the soil characteristics. After that, degradation processes become so extensive that further research is no longer feasible. Water and high temperatures damage DNA, making it impossible to extract genetic material from remains found in cremation burials,” said the VU Professor.

One of the key methods used in paleogenetics is the polymerase chain reaction (PCR) ‒ it employs specific markers, known as ‘primers’, which identify specific genetic targets from vast amounts of genetic material and information.

“In this case, we can use the lock-and-key analogy: the primers act as keys, while the targets function as locks. This genetic material is then multiplied to a level that can be analysed in the laboratory. The PCR technologies are applied very widely. In paleogenetics, specialised bioinformatics tools are employed to assess the authenticity and degradation of the material. It is crucial to determine whether the specific genetic material originates from the studied period or if it was introduced later. Specific technological approaches are used to assess the rate of spontaneous mutations, degradation, and other parameters,” revealed Prof. Jankauskas.

The process of the collection, preparation, and storage of samples is critical. This requires special laboratory conditions and protection from modern DNA, with the primary source of contamination being the researchers themselves.

“Here, again, the lock-and-key principle applies: if a marker identifies a molecule, it will multiply it. Scientists can never be sure whether the amplified DNA is truly ancient or introduced from their own presence. We are still setting up the new laboratory at the Medical Science Centre and training the scientists who will work there. It is estimated that preparing a single sample requires an entire pack of disposable gloves; if a researcher wearing a protective suit adjusts their glasses with gloved hands, the gloves must be discarded immediately. Once the “reactor” is up and running, access will be restricted to specially trained personnel ‒ even I plan to observe it only from behind glass,” remarked the scientist, highlighting the challenges involved.

"How much Neanderthal is there in you?"

Paleogenetics has uncovered many previously unknown facts, including new insights into human origins and migration into Europe. Until recently, much of the research on human evolution and migration routes has been carried out in Africa, where ancient genetic material is poorly preserved.

“Paleogenetics has opened up new opportunities to explore other regions and topics, including the link between us and Neanderthals. It turns out that Neanderthals are far more closely related to modern humans than previously thought. Some researchers even claim that they were genetically closer to us than brown and polar bears are to each other. Moreover, the species of modern humans and Neanderthals once even used to share common descendants. Approximately 4–5% of the genome of every European is composed of Neanderthal genes. So, we can all ask ourselves: “How much Neanderthal is there in me?” said the Professor.

Another important point is that Neanderthals were the forerunners of modern humans in Europe, though they were not our direct ancestors. Meanwhile, the forerunners of modern humans in East Asia were the Denisovans.

“This was determined not from bone remains but by analysing genetic data fragments – having extracted DNA, scientists identified a previously unknown human subspecies. It appears that at the same time, Earth was home to not just Homo erectus and Neanderthals but also to other human species,” explained Prof. Jankauskas.

These discoveries help us better understand migration patterns and physical human traits, as well as shed light on susceptibility to various diseases. Depending on the environmental conditions in which early humans lived, they adapted, and some of their genes have been passed down to us.

“We, as Europeans, inherited a predisposition to certain diseases from Neanderthals. This knowledge is crucial for developing personalised medicine, where treatments are tailored to an individual’s genetic structure and composition,” stated the scientist.

The settlement of Europe: a series of migration processes

Paleogenetic research has revealed that modern humans settling in Europe did not occur as a single event. The earliest settlers left no lasting genetic traces, as they eventually disappeared and were replaced by later waves of migration.

“During the last glacial period, the then population living in Europe sought refuge in isolated areas. One of the best-known hiding places was in the Iberian Peninsula, while the other was in the northern Balkans. Over thousands of years, these groups developed distinct genetic characteristics and later recolonised Central and Northern Europe,” noted the researcher.

Paleogenetic studies allow scientists to reconstruct the appearance of early humans. It is essential, though, to understand that these people were our predecessors who lived before us; however, they were not our direct ancestors.

“The very first studies on mitochondrial DNA, which is transmitted through the maternal line, show that these people were significantly different from us. One of the earliest known genetic markers is the haplogroup U5, which is now found in less than one-fifth of Lithuania’s population. These people ‒ hunters and gatherers ‒ were small, short, dark-haired, dark-skinned, light-eyed, and lactose intolerant,” listed the Professor.

Cultural developments have greatly influenced our evolution, with agriculture playing a key role in this process. It was introduced to Central Europe from the Fertile Crescent in Southeast Asia. The new settlers overshadowed the hunter-gatherer populations living in these regions.

“Over several thousand years, these people adapted to tolerate fresh milk. It is estimated that in Scandinavia, over 8,000 years, lactase enzyme activity in adults (along with lactose tolerance) increased from 5% to 80%. This happened because lactose tolerance offered significant advantages in such climatic conditions,” noted Prof. Jankauskas.

The first farmers to come to Europe did not impact the Baltic region. The haplogroup U5 still remains in our areas, representing the continuity of hunter-gatherer populations. Only at the end of the Stone Age, around 4,000 years ago, people from the steppes of present-day Ukraine arrived, introducing the Corded Ware culture.

“These people are linked to Indo-Europeans. They brought animal husbandry and, while partially overshadowing it, also integrated the genome of hunter-gatherers. We are unique because up to a quarter of our genome comes from ancient hunter-gatherers. Therefore, it is wrong to think of ourselves as solely Indo-Europeans, as if we are only descendants of the people coming from the Ukrainian steppes. These newcomers were distinct in appearance: they were taller, fair-skinned, light-haired, but had dark eyes,” said the scientist.

This process of migration and interbreeding took a very long time and had several stages. Paleogenomic research carried out over the past few years has provided more data on these processes. Currently, scientists are particularly interested in what happened during the Iron Age and the period of the Great Migration.

“With advancements in research and more affordable techniques, we can now trace familial relationships from the Iron Age. This could allow us to determine the social structure, understand the kinship of buried people, and estimate the size of their communities,” explained Prof. Jankauskas.

Paleogenomics helps explain the history of pathogens

Another area of paleogenomic research is the history of pathogens, with many fascinating and unexpected discoveries already made.

“One of the oldest genetic traces of the plague pathogen in Lithuania dates back to the period of the Corded Ware culture. Similar traces from the Stone Age have been found throughout Europe. Of course, this plague pathogen was not exactly the same as the one that caused the outbreaks in the 6th or 14th centuries. It was milder and did not cause such severe changes in organisms, nor did it clog the guts of infected fleas, and was harder to control. Thus, diseases also moved with people and acted as a factor of natural selection,” commented the researcher.

Prof. Jankauskas also shared how a researcher he knows at the Max Planck Institute in Germany studied the factors behind the massive mortality among the Aztecs in the 16th century, when 90% of the population perished. Previously, the common belief was that it was Europeans who brought smallpox, infecting the local population.

“This version was found in written sources. However, genetic research now reveals that salmonellosis, a bacterial disease affecting the intestinal tract, was the real culprit. Those who survived developed an immune system that is still beneficial today. One of the examples could be the ability of Aztec descendants – modern-day Mexicans – to safely consume street food in their country without any concern,” said the VU Professor.

We also have a similar case in Lithuania. In the Dominican Church, dozens of mummified remains have been preserved. When studying the genome of the pathogens found in these remains, scientists successfully sequenced the complete genome of the smallpox virus.

“This disease is now extinct. Comparing this material with data from other paleogenetic studies across Europe, we can see that smallpox became a serious threat to humans in the early 17th century when a specific mutation occurred. Its outbreak took countless lives during the 17th and 18th centuries until the smallpox vaccine was introduced. When people started to get vaccinated, this virus mutated numerous times, giving rise to many new strains,” revealed the scientist.

Our predisposition to certain diseases is a consequence of our biological history. This opens up possibilities for personalised medicine, where genetic history plays a crucial role.

“Genetic knowledge allows us to tailor medications for a specific population and even for a specific person. Since medicines will not only be suitable for a single person but also effective for the residents of a particular region, they will become less expensive. Of course, I hope that in the future, even fully personalised genome-based treatments will be accessible to many of us,” added Prof. Jankauskas.

Restoring extinct species is not the goal of paleogenetics

Paleogeneticists are often asked whether they could bring extinct species back to life. According to Prof. Jankauskas, while it is theoretically possible, the real question is: “But should we?”

“One biotechnology company in the US is currently attempting to resurrect the woolly mammoth. Their approach involves inserting extracted mammoth DNA into an elephant egg cell, hoping that a female elephant will give birth to a genetically engineered mammoth. Thus, this could perhaps allow other extinct bird and mammal species to be restored. However, although theoretical possibilities exist, the question is whether we have the necessary technologies and, ultimately, how much it will cost,” noted the researcher.

It is essential to understand that the goal of paleogenetics is not to restore extinct species but only to decode genomes. The road from decoding a genome to bringing a species back to life is very long. According to the Professor, this process could be likened to the publication of a book – having access to it does not mean everyone will know how to interpret it, as it requires knowledge and imagination.

“The study of disease pathogens is an even more sensitive issue. In some cases, genetic findings can be used for propaganda purposes. A few years ago, our colleagues from a Canadian university sequenced the smallpox genome from our provided samples. This disease is considered to have been eradicated, and frozen viruses can only be found in a few secure laboratories worldwide. Shortly after the findings were published, I received a phone call from a reporter who spoke Lithuanian with a strong Russian accent; he introduced himself as working for an independent Latvian TV station. They wanted me to talk about the smallpox research in a phone interview. Something felt off, so I immediately consulted a journalist I knew. It didn’t take long to realise that this reporter was not trustworthy, and our conversation would likely be edited and used for propaganda,” recalled the scientist.

When asked about the future of paleogenomics, Prof. Jankauskas highlighted the possibility of predicting and preventing various diseases before they arise and creating the necessary medications.

“In evolution, we are in a constant race with different pathogens. As the Red Queen from “Through the Looking Glass and What Alice Found There” said to Alice: “Now, here, you see, it takes all the running you can do, to keep in the same place.” Therefore, scientists working in the field of paleogenomics can definitely contribute to this,” concluded the VU Professor.