The Black Death wiped out a large portion of the world’s population in the 14th century, but a new study suggests that the plague was around much earlier than that. According to a press release from Eurekalert, scientists at the University of Copenhagen have analyzed Bronze Age DNA to find that the bacteria that caused the plague had the ability to infect humans 3,300 years before the infamous breakout.
The study, published in the journal Cell, reveals that the plague affected people as early as 4,800 years ago. Researchers sequenced the DNA extracted from tooth samples from European and Asian Bronze Age skulls to find evidence of the bacteria, Yersina pestis, which caused the Black Death. The bacteria were transmitted by fleas hitchhiking on the backs of rats, and were adept at evading the body’s natural defense systems.
According to the study’s head author, Eske Willerslev from the Center for GeoGenetics at the University of Copenhagen, “We found that the Y. pestis lineage originated and was widespread much earlier than previously thought, and we narrowed the time window as to when it developed. This study changes our view of when and how plague influenced human populations and opens new avenues for studying the evolution of diseases.”
Y. pestis earned notoriety during the Plague of Justinian, or the Black Death in the mid-1300s. The plague caused the death of roughly 50 percent of Europe’s population. It returned in the Third Pandemic, which affected China in the 1850s. The Plague of Athens occurred in ancient Greece 2,500 years ago, and the Antonine Plague was responsible for the eventual decline of Classical Greece and the defeat of the Roman army. Despite a lack of genetic evidence, many scientists think Y. pestis is responsible for the majority of these past epidemics.
Scientists think the plague was infecting people way earlier than anybody previously believed. Just a few months ago, researchers Willerslev, Kristian Kristiansen from the University of Gothenburg, and a number of other scientists published a genetic analysis of Eurasian populations in the Bronze Age, which occurred from 3000 BC to 1500 BC. The study revealed that the Bronze Age was full of large-scale migrations and dramatic shifts in population dynamics, which led to many of the present day populations throughout Europe and Asia.
According to one of the study’s co-authors, Morten Allentoft of the Center for GeoGenetics at the University of Copenhagen, “One of the scenarios we discussed was the idea that large epidemics could have facilitated such dynamics. Perhaps people were migrating to get away from epidemics or re-colonizing new areas where epidemics had decimated the local populations. Could it be, for example, that plague was present in humans already in these prehistoric times?”
Researchers analyzed 89 billion raw DNA sequences extracted from the teeth of 101 skulls of individuals who lived in Bronze Age Europe and Asia. The analysis revealed that Y. pestis DNA was present in seven of the individuals, who lived between the years between 2794 BC and 951 BC. The oldest-known ancestor of the Y. pestis strain is 5,783 years old.
The biggest evolutionary shift that led to the spread of the plague, the study suggests, was the development of a gene called Yersina murine toxin, or ymt. This gene allowed the bacteria to live in the gut of fleas without danger. With a safe and mobile host, the bacteria could hitchhike in the stomachs of fleas that lived on rats, which inevitably transferred to humans. The gene was found in one of the earliest Iron Age individuals, suggesting that fleas had the ability to transmit the disease as early as 3,700 years ago.
Y. pestis was also well suited for evading the defenses of its mammalian hosts. The immune system in humans and rats attacks pathogens with a protein called flagellin, which makes up many bacteria’s whip-like tails that help them locomote. Y. pestis strains have a specific mutation in the flhD gene, which prevents the expression of this protein. Without a biomarker telling the body’s immune system to launch an attack, Y. pestis exists without disruption in its hosts.
This mutation wasn’t presnt in the oldest DNA samples, and in the youngest sample, the flagella defense system was still in the process of developing in Y. pestis. This suggests that the disease wasn’t fully transmissible by fleas until the start of the first millennium BC.
“The underlying evolutionary mechanisms that facilitated the evolution of Y. pestis are still present today, and learning from this will help us understand how future pathogens may arise or develop increased virulence,” says co-author Simon Rasmussen from the Technical University of Denmark. The study makes it clear that it was entirely possible for fleas to transmit the disease to humans earlier than we once thought.
Researchers will continue to analyze ancient DNA samples to determine when exactly the plague made its debut in humans. The methods laid out by the study will also be useful for studying the evolution of other ancient diseases.