Plague in humans 3,300 years earlier than previously thought: study

Plague infections in humans were 3,300 years earlier than the historical record suggests, according to a report published Thursday in the U.S. journal Cell.

By sequencing the DNA of tooth samples from Bronze Age individuals from Europe and Asia, researchers discovered evidence of plague infections roughly 4,800 years ago.

But the ancestral plague would have been predominantly spread by human-to-human contact, until the bacterium that causes the disease, Yersinia pestis (Y. pestis), acquired key changes in virulence genes, allowing it to spread via fleas.

"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," senior author Eske Willerslev of the Center for GeoGenetics, University of Copenhagen, said in a statement.

Y. pestis was the notorious culprit behind the sixth century's Plague of Justinian, the Black Death, which killed 30 to 50 percent of the European population in the mid-1300s, and the Third Pandemic, which emerged in China in the 1850s.

Earlier putative plagues, such as the Plague of Athens nearly 2,500 years ago and the second century's Antonine Plague, have been linked to the decline of Classical Greece and the undermining of the Roman army.

However, it has been unclear whether Y. pestis could have been responsible for these early epidemics because direct molecular evidence for this bacterium has not been obtained from skeletal material older than 1,500 years.

In the new study, the researchers analyzed ancient genomes extracted from the teeth of 101 adults dating from the Bronze Age and found across the Eurasian landmass from Siberia to Poland.

They discovered Y. pestis DNA in seven of these individuals, whose teeth were dated between 2794 BC and 951 BC (early Iron Age).

However, six of the seven plague samples were missing two key genetic components found in most modern strains of plague: a "virulence gene" called ymt, and a mutation in an "activator gene" called pla.

The ymt gene, known to protect the pathogen inside the flea gut and thereby enable the spread of plague to humans via an insect vector, was present in the Y. pestis genome from the Iron Age individual, suggesting that plague became transmissible by fleas between approximately 3,700 and 3,000 years ago.

The mutation in the pla gene allows Y. pestis bacteria to spread across different tissues, turning the localized lung infection of pneumonic plague into one of the blood and lymph nodes.

This led the researchers to believe that early strains of plague could not cause the bubonic form of the disease, which affects the lymphatic immune system, and inflicts the infamous swollen buboes of the Black Death.

Consequently, the plague that stalked populations for much of the Bronze Age must have been pneumonic, which directly affects the respiratory system and causes desperate, hacking coughing fits just before death. Breathing around infected people may lead to inhalation of the bacteria, the crux of its human-to-human transmission.

"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," said co-first study author Simon Rasmussen of the Technical University of Denmark.

In future studies, the researchers will look for evidence of plague in other geographic regions and time periods to get a better grasp of the history of this disease. Endit