The study by an international team including researchers from the universities of Copenhagen and Cambridge, using ancient DNA showed that plague has been endemic in human populations for more than twice as long as previously thought.
Ancestral plague would have been predominantly spread by human-to-human contact - until genetic mutations allowed Yersinia pestis (Y pestis), the bacteria that causes plague, to survive in the gut of fleas, researchers said.
These mutations, which may have occurred near the turn of the 1st millennium BC, gave rise to the bubonic form of plague that spreads at terrifying speed through flea - and consequently rat - carriers, researchers said.
Before its flea-borne evolution, however, researchers say that plague was in fact endemic in the human populations of Eurasia at least 3,000 years before the first plague pandemic in historical records (the Plague of Justinian in 541 AD).
The new evidence that Y pestis bacterial infection in humans actually emerged around the beginning of the Bronze Age suggests that plague may have been responsible for major population declines believed to have occurred in the late 4th and early 3rd millennium BC, researchers said.
Researchers analysed ancient genomes extracted from the teeth of 101 adults dating from the Bronze Age and found across the Eurasian landmass.
They found Y pestis bacteria in the DNA of seven of the adults, the oldest of whom died 5,783 years ago - the earliest evidence of plague.
Previously, direct molecular evidence for Y pestis had not been obtained from skeletal material older than 1,500 years.
The ymt gene protects the bacteria from being destroyed by the toxins in flea guts, so that it multiplies, choking the flea's digestive tract. This causes the starving flea to frantically bite anything it can, and, in doing so, spread the plague.
The mutation in the pla gene allows Y. Pestis bacteria to spread across different tissues, turning the localised lung infection of pneumonic plague into one of the blood and lymph nodes.
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