Marcelo Briones, a biologist from the Federal University of São Paulo (UNIFESP), set out to prove that it is possible to detect viral infections in the skeletons of Neanderthals (Homo sapiens neanderthalensis), a hominid species that went extinct some 30,000 years ago. And he achieved what he described as a proof of concept, according to an article published in the journal Viruses at the end of May. He was surprised by the positive response to his article, which was covered by renowned international media outlets, such as the popular scientific magazine New Scientist and the journalism section of Science.
The discovery made waves because the Neanderthals that apparently carried adenoviruses, herpesviruses, and papillomaviruses — all of which still circulate in humans today — lived around 50,000 years ago in what is now Siberia. The finding represents the oldest documented human viral infection, far surpassing the previous record from 31,000-year-old human (H. sapiens) bones.
The study was carried out using genome sequences available in existing databases. “We selected two individuals from the Chagyrskaya Cave because the samples were collected more recently and great care was taken to avoid contamination, plus the data was quite complete, especially for one of them, called number 7,” explains Briones. What he was looking for was short segments of sequenced DNA. “This data is considered garbage; researchers usually discard highly fragmented genetic sequences.” But they are most likely remnants of virus DNA, which have naturally smaller genomes and are more easily broken because they are not protected within cell nuclei.
Briones explains that the samples, removed from the fossils with a small drill, contain DNA that originally came from the bone itself and that in life would also have been in the adjacent tissues and in the blood in vessels inside the bone. This blood would theoretically harbor the viruses. The specific types detected characteristically remain in the body for long periods, beyond the acute infection stage.
The UNIFESP group’s study was novel in its use of a variety of bioinformatics and statistical tools to prove that the detected sequences actually correspond to the genome of ancient viruses, rather than recent contaminations or sections incorporated into Neanderthal DNA. “Nobody had done this noise control before,” says Tábita Hünemeier, a geneticist from the University of São Paulo who was not involved in the study. “It’s a very robust way of showing that it really is virus DNA.”
Wikimedia CommonsSkulls of a modern human (left) and a Neanderthal (right): the extinct species was stouter, possibly with a larger brainWikimedia Commons
She works at the Laboratory of Archaeology and Environmental and Evolutionary Anthropology (LAAAE), based at the University of São Paulo’s Museum of Archaeology and Ethnology (MAE-USP). The LAAAE is Brazil’s first archaeogenetics lab, headed by archaeologist André Strauss and bioanthropologists Rui Murrieta and Rodrigo Oliveira. Hünemeier notes that a technique used at the lab, in which genetic samples are enriched with the desired sequences to study them better, would be a valuable addition to Briones’s work.
The article was so well received largely due to its potential contribution to our understanding of the extinction of Neanderthals. “They were stouter than H. sapiens and they had bigger brains,” says Briones, inferring that they were highly capable. “It is unlikely that they were eliminated in battle.”
He believes it makes more sense that they succumbed to viruses. The hypothesis was first proposed in 2010 by German virologist Horst Wolff and American biologist Alex Greenwood, both based in Germany, in an article published in the scientific journal Medical Hypotheses. The pair postulated that after spending around 200,000 years on the continent that is now Europe and Asia, the Neanderthal immune system adapted to the diseases present in that environment and was not prepared for the viruses introduced around 80,000 years ago by human migrations from Africa. “Homo sapiens were in close contact with other primates that did not exist in Europe, meaning they had much more contact with zoonoses,” explains Briones. The German researchers did not research the topic any further and were therefore unavailable to comment on the current study.
“These viruses are not lethal to us,” points out Hünemeier. “But we don’t know if the same was true for Neanderthals.” She believes scientists need to look for a sign of natural selection by analyzing several individuals to ascertain the evolutionary context. Briones argues that even a nonfatal infection could be detrimental to the life and reproductive capacity of the hominids, leaving them at a disadvantage compared to their sapiens counterparts.
The complexity is heightened by the fact that several human species coexisted at the time—interbreeding between Homo sapiens and Neanderthals has been genetically confirmed. These reproductive encounters became more frequent between around 47,000 and 40,000 years ago, according to an article by Indian evolutionary biologist Priya Moorjani of the University of California, Berkeley, and colleagues, shared as a preprint on bioRxiv on May 13. The researcher declined to give Pesquisa FAPESP a comment on the results because the paper has not yet been formally published.
“Neanderthals lived in an area that stretched from what is now England to what is now Mongolia, but always in small family groups,” explains Hünemeier. They practiced funerary rituals and produced art in the form of paintings and ornaments, such as necklaces, behavior that archaeologists interpret as representative of sophisticated societies. They were not aggressive and did not produce any throwing weapons, which may have put them at a disadvantage compared to Homo sapiens, who made bows and arrows. “Disease may have had a strong impact, but we have no way of knowing.” Briones’s results could pave the way for more in-depth investigations in the future. He intends to expand the study by analyzing genetic sequences from other Neanderthals and Homo sapiens, both contemporary and more recent, to look for the presence of viruses.
Project
Investigation of elements induced by the vaccine response in individuals undergoing clinical trials of the ChAdOx1 nCOV-19 vaccine (nº 20/08943-5); Grant Mechanism Thematic Project; Principal Investigator Luiz Mário Ramos Janini (UNIFESP); Investment R$5,543,378.48.
Scientific articles
FERREIRA, R. C. et al. Reconstructing prehistoric viral genomes from Neanderthal sequencing data. Viruses. vol. 16, no. 6, 856. may 27, 2024.
IASI, L. et al. Neandertal ancestry through time: Insights from genomes of ancient and present-day humans. bioRxiv. may 13, 2024.
WOLFF, H. & GREENWOOD, A. D. Did viral disease of humans wipe out the neandertals? Medical Hypotheses. vol. 75, no. 1, pp. 99–105. july 2010.
