Inside a pair of 31,000-year-old baby teeth, scientists discovered DNA remnants from several viruses and used that genetic material to reconstruct the pathogens' evolutionary history. Their analysis suggests that human adenovirus C (HAdV-C), a species of virus that typically causes mild, cold-like illnesses in children, may have originated more than 700,000 years ago, long before Homo sapiens walked the Earth, the team reported in a recent study, posted June 28 to the preprint database bioRxiv, which has not yet been peer-reviewed. Still, not everyone is convinced by the findings. "The authors find a relatively ancient date before the emergence of our own species," said Sébastien Calvignac-Spencer, an evolutionary biologist at the Robert Koch Institute in Germany. "I think it is plausible but ... I would consider their analyses as preliminary," Calvignac-Spencer, who was not involved in the study, told Live Science in an email. The study authors extracted two "nearly complete" adenovirus genomes from the baby teeth, providing a unique but very small sample of viruses upon which to base their analyses, Calvignac-Spencer said. Analyzing younger adenoviruses, dating a few thousand years old, could help the team validate their estimate of when HAdV-Cs first emerged, he noted. That said, ancient adenovirus samples don't crop up every day. The baby teeth used in the study came from a remarkable archaeological site in northeastern Siberia called Yana "Rhinoceros Horn Site" (RHS), where an arrow foreshaft made of woolly rhinoceros horn was once found, according to a 2004 report in the journal Science. The archeological site, located about 300 miles (480 kilometers) north of the Arctic Circle, provides some of the earliest direct evidence of humans living in the high Arctic, NBC News reported. Archaeologists have found stone tools, ivory weapons and the bones of butchered mammoths, bison and bears at the site. The only human remains discovered at Yana RHS are three fragmented baby teeth, which came from two different children who shed them when they were between 10 and 12 years old, according to a 2019 report in the journal Nature. Viruses can enter teeth via the bloodstream and remain preserved in the tough tissue for many thousands of years, said first author Sofie Nielsen, who was a doctoral student at the University of Copenhagen at the time of the study. And unlike bones in the body, teeth don't ever regenerate — they retain the same cells over time, so they provide a cumulative record of all the pathogens a person has encountered, she told Live Science. In this case, the ancient baby teeth supplied a record of early childhood infections, and the frigid Arctic environment likely helped to preserve both the teeth and the viral DNA inside, Nielsen said. To extract the viral DNA, the research team had to completely decimate the tooth tissue. Even the tough teeth and cold climate could not completely shield the viral DNA from degradation, so the genomes became fragmented over time. To piece the broken genomes back together, the team analyzed each bit of DNA and compared the short genetic sequences with reference genomes from modern-day viruses. They identified the two ancient genomes as HAdV-Cs, one of the seven known species of adenovirus, A through G. The team found that the ancient genomes shared many similarities with modern-day adenoviruses that were circulating between the 1950s and 2010s. For instance, all the modern HAdV-C viruses share the same genetic "backbone" but show diversity in a few key genes, including ones that help the viruses avoid detection by the host immune system. These slight differences place the viruses into six distinct subtypes; for example, HAdV-C1 and HAdV-C2 are different subtypes under the HAdV-C umbrella. The team found that the ancient adenoviruses shared most of their genetic backbone with the modern viruses, and that the two ancient genomes fit neatly into the established "C1" and "C2" subtypes. "The extraordinary thing is that … they are more similar to the modern type two and type one than they are to each other," Nielsen said. In other words, despite both being 31,600 years old, the two ancient genomes matched modern viruses within their subtype better than they matched one another. This finding hints that the various adenovirus subtypes began diverging from one another many thousands of years ago, long before they made their way into baby teeth of two youngsters in ancient Siberia, according to Nielson and her colleagues. By again comparing the modern genomes to the ancient ones, the team generated a rough estimate of when HAdV-Cs split from all other adenoviruses. "These dates are very uncertain, because we have so few samples," Nielsen said. "But it seems like they were split at least 700,000 years ago." This estimate places the origin of HAdV-Cs before the emergence of modern humans, which occurred roughly 300,000 years ago, Live Science previously reported. In their report, the study authors suggest that the migratory patterns and cross-species interactions of our hominin ancestors may have helped shape the evolution of these adenoviruses, but if that happened and how remains highly uncertain. "We have shown ourselves that other HAdVs — HAdV-Bs and Es — were probably transmitted to the human lineage by gorillas and chimps," Calvignac-Spencer told Live Science, referencing previous research by his own lab. "We found that some of these transmission events probably predated our species but others did not." The discovery of more ancient adenovirus samples would help researchers pinpoint when HAdV-Cs first began infecting our human ancestors, and which species the pathogens passed through on their way to the human lineage, he said. "We have such a long span of time where we know nothing," Nielsen said. Ideally, future analyses would not only include adenoviruses of many ages but also adenoviruses from many different geographical locations, she noted. "For sure, more data is always better." Source
