Plague Began Infecting Human Populations Earlier Than We Thought, Ancient DNA Reveals

Ancient DNA specimens revealed that plague in human populations has been around twice as long as previously thought and the disease did not begin as flea-borne, according to a team of researchers from the University of Copenhagen, in Denmark and University of Cambridge, in the UK.

The new research revealed that the ancestral plague would have been spread significantly through human-to-human contact, until genetic mutations allowed the pathogen Yersinia pestis (Y. pestis), the bacteria that causes plague, to survive in the gut of fleas, according to a news release.

The researchers claimed that these mutations occurred around the first millennium B.C., which increased the spread of the bubonic form of plague through fleas, and subsequently rat carriers. The bubonic plague was responsible for pandemics that gobbled global populations, including the Black Death, which wiped out half of Europe's population in the 14th century. 

"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 and how it developed," said Professor Eske Willerslev, senior author of the study, from Cambridge University's Department of Zoology.

"The underlying mechanisms that facilitated the evolution of Y. pestis are present even today. Learning from the past may help us understand how future pathogens may arise and evolve," he added.

The researchers believe that before the flea-borne evolution, plague was endemic in human populations in Eurasia 3,000 years before the first historical plague pandemic (the Plague of Justinian in 541 A.D.).

The new evidence showed that the Y. pestis bacterial infection emerged in humans at the beginning of the Bronze Age. The researchers assessed ancient genomes from the teeth of 101 adults from Bronze Age Siberia. The Y. pestis bacteria was found in the DNA of seven adults - with the oldest one having died about 5,783 years ago - as the earliest evidence of plague. Initially, molecular evidence was not obtained from skeletal specimens older than 1,500 years.

The researchers found that the plague changed over time. Of the seven plague specimens, six of them were missing two key genetic components found in modern strains of plague, a "virulence gene," called ymt, and a mutation in an "activator gene," called pla. The ymt gene protects the bacteria from being destroyed by toxins in flea guts, which allows it to multiply and causes choking to the flea's digestive tract.

As a result, the starving flea bites at anything that it finds, which ultimately spreads the plague. The mutation in the pla gene allows Y. pestis bacteria to spread to different tissues, which changes localized lung infection of pneumonic plague into one of the blood and lymph nodes, according to the researchers. 

The plague ridden population from the Bronze Age may have been pneumonic, which directly affects the respiratory system and causes intense, hacking coughing fits just before death. Also, breathing around infected people leads to inhalation of the bacteria, which is the main channel of its human-to-human transmission.

"The Bronze Age was a period of major metal weapon production, and it is thought increased warfare, which is compatible with emerging evidence of large population movements at the time. If pneumonic plague was carried as part of these migrations, it would have had devastating effects on small groups they encountered," said Dr Marta Mirazón-Lahr, co-author of the study, from Cambridge's Leverhulme Centre for Human Evolutionary Studies (LCHES).

"Well-documented cases have shown the pneumonic plague's chain of infection can go from a single hunter or herder to ravaging an entire community in two to three days," said Mirazón-Lahr. 

The seven ancient genomes specimens reveal that the Y. pestis had both of the key genetic mutations, which gives an approximate timeline for the plague.

"Every pathogen has a balance to maintain. If it kills a host before it can spread, it too reaches a 'dead end'. Highly lethal diseases require certain demographic intensity to sustain them," said Professor Robert Foley, co-author of the study from Cambridge's LCHES.

"The endemic nature of pneumonic plague was perhaps more adapted for an earlier Bronze Age population. The Bronze Age is the edge of history, and ancient DNA is making what happened at this critical time more visible," Foley said.

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