The first people to step foot in the Americas were harboring a sliver of DNA from two extinct Eurasian human groups: the Neanderthals and the Denisovans, a new study finds. This genetic relic could have helped the earliest Americans fight diseases they encountered in their new environment, the researchers proposed.
Everyone alive today is “a result of like three different species coming together,” study co-author Fernando Villanea, a population geneticist at the University of Colorado Boulder, told Live Science.
“What we think has happened is that humans had this archaic variation,” study co-author Emilia Huerta-Sanchez, a population geneticist at Brown University, told Live Science. As people expanded into the Americas, they did not have to wait to develop new mutations to fight off new pathogens and could instead draw from the arsenal of genetic variants they gained from other human groups, she said.
In the new study, published Thursday (Aug. 21) in the journal Science, the researchers detailed their analysis of MUC19, a protein-coding gene with various functions, including coding for the consistency of mucus. They found that 1 in 3 Mexicans alive today has an MUC19 gene similar to that of Denisovans, a mysterious group of ancient humans who lived throughout Asia from about 200,000 to 30,000 years ago.
Research into MUC19 in Indigenous Americans has focused on two different aspects. One set of researchers previously showed that people with Indigenous American ancestry carry a high number of ancient human variants of MUC19, whereas the other set found that the MUC19 gene as a whole became more common over time in North American Indigenous populations because it was evolutionary advantageous.
But in the new study, the researchers discovered that the length of the Denisovan MUC19 DNA segment in Indigenous Americans has increased over time and that the variant hitched a ride from Neanderthals in an Oreo-like gene sandwich, Villanea said in a statement. This is the first time scientists have found a Denisovan gene that came to humans via Neanderthals.
“It’s wild,” Villanea said. “Is this the only instance of this happening, or are there more? We are still trying to figure [it] out.”
Related: ‘More Neanderthal than human’: How your health may depend on DNA from our long-lost ancestors
A DNA sandwich
To test whether the Denisovan-specific variants of MUC19 were beneficial for Indigenous Americans, the team compared the genetic data available on modern Mexican, Peruvian, Colombian and Puerto Rican individuals from the 1000 Genomes Project with the genetic sequences of 23 Indigenous people, most of whom lived in the Americas prior to the 13th century, as well as three Neanderthals and one Denisovan.
The team found that modern-day Mexicans had the highest frequency of the Denisovan-specific MUC19 variants, with about 33% of the population carrying this version of the gene. About 20% of Peruvians carried the variant, whereas only around 1% of Colombians and Puerto Ricans did. The researchers think this is because, on average, Mexicans have more Indigenous American DNA in their genomes than the other populations do.
When the team investigated which archaic human group had passed on these gene variants, they were surprised to see that the Denisovan section of the gene was sandwiched between Neanderthal-specific DNA. The most likely explanation for this is that Neanderthals first acquired these variants from mating with Denisovans, and when Neanderthals later mated with modern humans, they passed on this surprise genetic parcel, the researchers said.
“The researchers took this complex pattern, and they were able to parse it out in the context of past human demographic events,” Ripan Malhi, a molecular anthropologist at the University of Illinois at Urbana-Champaign who was not involved in the new study, told Live Science in an email. The work is impressive, he said, and now we need to learn more about the function of the Denisovan MUC19 gene.
This is the next step for Villanea and his team, who are planning to look at new research collections of biological samples that have both genomic and trait data from Latino or Indigenous American people to see how the Denisovan-specific variants affect protein function.
Depending on exactly what the Denisovan MUC19 variant does, it may help the immune system fight some specific pathogens or regulate particular immune responses, Huerta-Sanchez said. “We suspect that it’s going to be doing something drastically different” from what the modern human variant does, Villanea said.
