We catch new flu viruses from ducks and pigs. And Ebola, the disease that's got the world worried at the moment, may have originated in bats. Now, a study of microbial DNA isolated from 1000-year-old Peruvian mummies blames seals for spreading tuberculosis (TB) to humans in South America long before European settlers arrived.
"This work provides an entirely new vista on the arrival of [TB] in the New World, and also the potential role of sea mammals in the global dissemination of the TB [bacteria]," says Stephen Gordon, a microbiologist at University College Dublin who was not involved in the work. The analysis also indicates that TB as a human disease is much younger than researchers have thought.
Even though TB kills more than a million people per year, there’s still much debate about when Mycobacterium tuberculosis, the bacterium that causes it, first infected humans and how it spread. One early idea was that it's a relatively young disease that spread from cows to humans in the Stone Age, less than 10,000 years ago. More recently, studies have shown huge diversity in the DNA of TB strains from around the world, and particularly in Africa; that suggests TB arose in humans 100,000 years ago and was spread around the world and into other animals as our ancestors migrated out of Africa, says Johannes Krause, a geneticist from the University of Tübingen in Germany.
How TB reached the Americas has also been contentious. The M. tuberculosis strains in the Western Hemisphere all look like those from modern Europe, suggesting early explorers brought the disease with them. But several mummies that predate Columbus’s arrival in the New World have the bone changes indicative of TB, suggesting the bacteria arrived before Europeans did.
Indeed, medical microbiologist Helen Donoghue of University College London and her colleagues found Mycobacterium DNA in a 17,000-year-old bison fossil from Wyoming more than a decade ago. But others who worked on a different part of the same bone did not turn up any bacterial DNA and called Donoghue’s results into question. Subsequently, organic chemist David Minnikin from the University of Birmingham in the United Kingdom discovered telltale fatlike molecules called lipids in the same bone and in other large mammal fossils that belong to Mycobacterium. Minnikin thinks that ancient Americans were infected with TB from eating mastodon, bison, and other large mammals, which may have carried the disease to the Americas over on the land bridge between Siberia and Alaska.
In the new study, Krause used DNA sequencing to get to the bottom of these mysteries. He and his colleagues isolated and tested DNA from 68 ancient South American human bones over varying ages showing signs of decay and deformity characteristic of TB. They found DNA from TB bacteria in bones from three different people, confirming the diagnosis; they even pieced together much of the bacterial genome for each.
“The paper clearly and convincingly shows that TB was in the Americas prior to [European] contact,” says Ruth Hershberg, an evolutionary microbial genomics researcher at the Israel Institute of Technology in Haifa, who was not involved with the work.
Krause and his colleagues compared the three ancient American genomes with a Mycobacterium genome isolated from a 200-year-old Hungarian mummy and the genomes of modern TB bacteria, both from humans and from more than 250 other species. From these data, they estimated the mutation rate in the bacteria, which allowed them to determine that the last common ancestor of all human strains lived 5000 to 6000 years ago, they report online today in Nature. "We can now show the mutation rate is about 10x faster" than previously proposed, Krause says.
To learn how TB got to the Americas, Krause’s team counted up the differences in the TB bacterial genomes’ individual “letters,” or base pairs. Fewer differences means the genomes are more closely related.
The genomes from the Peruvian mummies proved closest in sequence to a TB stain that infects marine mammals. That's why Krause proposes that more than 1000 years ago, Peruvians hunting seals or sea lions caught TB from eating meat. The seals likely got the disease from some other unidentified animal in Africa and brought it across the ocean to South America, the researchers suggest. The seal-like TB bacterium was presumably replaced by a more virulent strain imported later by the Europeans, and it disappeared.
The marine route is a plausible and convincing explanation," says Stewart Cole, a microbiologist at the Swiss Federal Institute of Technology in Lausanne. In a zoo, a tapir once caught TB from a seal, so it's definitely possible, adds Thierry Wirth, who uses genomics to trace the history of infectious diseases at the National Museum of Natural History in Paris.
But both say it's not clear whether this was the only introduction in the Western Hemisphere. The microbes may still have crossed the Bering Strait in infected bison or people as well, Cole says. "It’s too big a jump to say all tuberculosis in South America is that young," Donoghue adds. She and other researchers think that Krause needs to look for seal-like TB bacteria in more ancient American samples from more locations. The critics also question the timing of the origin of TB in humans, which upsets the latest thinking that the disease may have been with us for a 100,000 years, arguing that Krause and his colleagues need a better way to calibrate the mutation rate. Nevertheless, "this work opens up a number of new leads to be followed up on," Gordon says.