The Black Death may have an unusual origin, according to a new study of one of the most famous and deadly epidemics of all time. Just a pair of changes in the genetic code of bacteria could have turned a fairly harmless stomach bug into a deadly pathogen.

Yersinia pestis evolved, gaining the ability to cause pneumonic plague in human beings. This form of the disease infects lungs and can be spread to other people when victims sneeze. The second mutation greatly increased the severity of the disease. It was only after that genetic change that the deadly disease we know today as the Black Death was able to easily cause death in people.

The black death (also known as the bubonic plague) took the lives of between 75 and 200 million people between the years 1346 and 1353. During the middle of the 14th century, only about 450 million people lived worldwide, so this epidemic greatly reduced the human population at the time.

The pathogen only evolved between 5,000 and 10,000 years ago, from another species of bacteria, Yersinia pseudotuberculosis, which produces mild symptoms in people infected with the microorganism. This progenitor species, which is still around today, was examined by researchers, who compared it with the bacteria responsible for the black death. They found the deadly bacteria contained a gene for a protein called PLA protease that is not present in the older species of microorganism.

These two alterations in the genetic code provided the bacteria with the ability to cause a quick-killing version of the bubonic plague, but it could not spread far. However, a change in an amino acid gave the microorganism the ability to create a pandemic. This mutation provided the bacteria with a way of more easily reaching the bloodstream, spreading the infection around the body of victims.

"It turns out that the ancestral variant of PLA reduces the ability of the bacteria to get into the deeper tissues by about 100 times compared to the modern variant. This single amino acid change was necessary for Yersinia pestis to cause modern bubonic plague," Wyndham Lathem of the Northwestern University Feinberg School of Medicine said.

The great loss of life during the bubonic plague resulted in many survivors receiving inheritances that played a major role in ending the practice of serfdom. This, in turn, freed up time for the rediscovery of science, which helped to bring about the Renaissance.

By studying how these mutations affected human health, researchers hope to learn more about modern disease.

Analysis of the genetic changes in bacteria which led to the black death was published in the journal Nature Communications.

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