One of civilization's most prolific killers, it followed humans for thousands of years without their knowledge. The plague-causing bacterium Yersinia pestis is thought to be responsible for up to 200 million deaths throughout human history.

Scientists have long assumed that the deadly disease began infecting humans shortly before the earliest known epidemic.

But paleogenetic research reveals that the plague has been with us for more than millennia: Ancient DNA (aDNA) of the bacteria was recovered from human skeletons 4,900 years old. This means that people were dying from contracting the plague at least 3,000 years before there was any archaeological or historical evidence of an epidemic.

But why didn't these earlier infections lead to devastating outbreaks like the Black Death? It seems the answer is part biological - genetic mutations of the bacteria itself - and part cultural - changes in human lifestyles that encouraged the spread of the disease. Scanning electron micrograph of Yersinia pestis bacteria (NIAID / Flickr , CC BY)

To identify cases of ancient plague, researchers extracted aDNA from the dental pulp chamber of a skeleton and searched for the genetic code of the bacteria Y. pestis. If the fossil teeth contain Y. pestis DNA, it is safe to assume that this person died of plague.

Several studies have found plague victims who lived nearly 5,000 years ago - more than 3,000 years before the first known plague epidemic.

Pathogen aDNA analysis also revealed how the Y. pestis bacterium evolved over time. The oldest genomes recovered belong to a now-extinct strain that lacked certain mutations that made the plague so contagious to humans. For example, later strains of Y. pestis developed a gene that allows the bacterium to efficiently infect fleas - the maincarriers of the disease in recent times - Older samples of Y. pestis lack the gene.

So far, the oldest plague genome recovered with these mutations dates back to around 1800 BC from the Samara Valley, Russia. The mutations have also been identified in an Iron Age skeleton from Armenia that has been dated to around 950 BC.

It appears that the most contagious form of plague has been infecting humans for nearly 4,000 years. But there are no indications in the archaeological record of epidemics in the ancient societies of Russia and Armenia - despite the fact that some individuals died from the highly contagious strain of plague.

It is possible that outbreaks occurred, but the evidence simply has not yet been found. For example, if future excavations were to uncover a series of mass graves that differed from the usual burial customs of these cultures, this might suggest a social disturbance consistent with an epidemic. An early 18th century mass grave of plague victims in Martigues, France (S. Tzortzis , CC BY)

Or perhaps the bacterial strains, although genetically similar to known plagues, lacked some other critical mutation, as yet unidentified. However there could also be another explanation, related to the behavior of infected people. Did the ancient people of the Samara Valley and Armenia live in a way that protected them from the plague - perhaps without even knowing it?

Researchers investigated whether populations in the Samara Valley of 1800 BCE and Iron Age Armenia behaved differently from people in the Justinian Empire in crucial ways. They first established conditions that make a population more or less vulnerable to an outbreak, identifying criteria known to be associated with plague, or how contagious the bacteria is.

Population density is important; the number of people in contact with an infected individual affects the rate at which the disease spreads.

Permanent agricultural settlements accumulate food storage and waste, which supports the co-habitation of rodent species. These rodents are ideal hosts for fleas that harbor plague bacteria.

Because East Asia is the likely geographic source of the plague, regular trade with the region is another factor. The researchers also examined reliance on horses, because some scholars suggest - though it has yet to be tested biologically - that the animals carry natural immunity to the plague. Regular contact with horses could reduce the population's susceptibility to the disease.

They then compare three populations based on these six criteria using archaeological and historical data.For the Justinian Plague, they focused on Constantinople, the capital of the Justinian Empire and an epicenter of the outbreak.The culture of Constantinople created a perfect storm of conditions for an epidemic.

It was a congested urban center with a population of over 500,000 people, or 140 individuals per acre. All of Constantinople's staple foods, including grain, were shipped from surrounding areas and stored in large warehouses, creating an ideal breeding ground for rodents. The flour trade also introduced the mouse species - Rattus rattus - from India that laterwould be identified as the main carrier of fleas harboring the plague.

In contrast, lifestyles in Samara and Armenia may have kept the epidemic at bay.

These populations were significantly more mobile and less congested than the urban population of Constantinople. The population of Samara shows little evidence for agriculture and tended to occupy small settlements of extended families. These communities managed shared herds, and the horse tools found on their characteristic burial mounds suggest that theanimals were highly valued. Remember, horses may have had some natural immunity to disease.

Due to changing local powers, Armenia seems to have been home to farmers as well as nomadic shepherds. Generally, however, archaeologists assume that the populations practiced livestock keeping, which would have made the people substantially more mobile and dispersed than the inhabitants of Constantinople.

Less congestion would have made it more difficult to contaminate neighboring villages. In the absence of agriculture, Samara could not have supported human-dependent rodents, as Constantinople did. Both populations potentially benefited from a high ratio of horses to people.

While Samara and Armenia saw occasional victims of the plague, the structure of their societies probably protected them from the devastation that befell Constantinople. Byzantine Emperor Justinian presided over a sprawling metropolis in Constantinople. (Hein Nouwens / Shutterstock.com)

While encouraging economic and technological gains, urban development and trade created ideal conditions for an epidemic in Constantinople. The vulnerability to plague was an unintended consequence of the lifestyle of this society.

However, it seems that previous cultures unwittingly protected themselves from the same threat.

The harsh reality is that it is extremely difficult, if not impossible, to control a pathogen, its possible mutations or its next outbreak. But understanding how human behaviors affect the spread and virulence of a disease can inform preparations for the future.

As a society, we can take organized steps to reduce the spread of infection, whether by limiting overcongestion, controlling food waste, or restricting access to contaminated areas. Human behaviors are as critical to our disease susceptibility as the characteristics of the pathogen itself.

SOURCE / The Conversation