Plague Infected Humans Much Earlier Than Previously Thought

Plague infections were common in humans 3,300 years earlier than the historical record suggests, reports a study published October 22 in Cell.

1By sequencing the DNA of tooth samples from Bronze Age individuals from Europe and Asia, the researchers discovered evidence of plague infections roughly 4,800 years ago. But it was at least another thousand years until the bacterium that causes the disease, Yersinia pestis, acquired key changes in virulence genes, allowing it to spread via fleas and evade the host immune system.

Assistant professor Morten Allentoft and professor Eske Willerslev from Center for GeoGenetics are two of the study authors.

“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,” says senior study author Eske Willerslev of the Center for GeoGenetics, University of Copenhagen. “This study changes our view of when and how plaque influenced human populations and opens new avenues for studying the evolution of diseases.”

Based on their recent work, Willerslev and his team suspected that the plague could have shaped human populations much earlier than previously thought. A few months ago, they published a high-profile population genomics study of Eurasian individuals from the Bronze Age (c. 3000 BC to 1500 BC), which they showed was a highly dynamic period involving large-scale migrations and population replacements that were responsible for shaping major parts of present-day demographic structure in both Europe and Asia. But the reason for these migrations was not clear.

CoverSuggestion2“One of the scenarios we discussed was the idea that large epidemics could have facilitated such dynamics,” says study co-first author Morten Allentoft of the Center for GeoGenetics, University of Copenhagen. “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?”

To answer this question, the researchers screened 89 billion raw DNA sequence reads obtained from the teeth of 101 Bronze Age individuals from Europe and Asia. These teeth were obtained from various museums and archaeological excavations. They discovered Y. pestis DNA in seven of these individuals, whose teeth were dated between 2794 BC and 951 BC (early Iron Age). Evolutionary analysis revealed that the most recent common ancestor of all known Y. pestis strains is 5,783 years old—thousands of years older than previous estimates.

“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-first study author Simon Rasmussen of the Technical University of Denmark. “Additionally, our study changes the historical understanding of this extremely important human pathogen and makes it possible that other so-called plagues, such as the Plague of Athens and the Antonine Plague, could have been caused by Y. pestis.”

This project was funded by the European Research Council, the Marie Curie Actions of the European Union, the Villum Foundation, the University of Copenhagen, the Danish National Research Foundation, and The Lundbeck Foundation.

Cell, Rasmussen and Allentoft et al.: “Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago”