What disease caused the Plague of Justinian?

The Plague of Justinian (541–542) was a pandemic that afflicted the Eastern Roman (Byzantine) Empire, especially its capital Constantinople, the Sassanid Empire, and port cities around the entire Mediterranean Sea. One of the greatest plagues in history, this devastating pandemic resulted in the deaths of an estimated 25 million to 50 million people.

The Plague of Justinian is generally regarded as the first recorded instance of bubonic plague. This conclusion is based on the historical description of the clinical manifestations during the epidemic and the detection of Yersinia pestis DNA from human remains at ancient grave sites dated to that period. A genetic study of the bacterium causing bubonic plague based on samples taken from the remains of 14th-century plague victims in London and a survey of other samples suggests that the Plague of Justinian and others from antiquity arose from either now-extinct strains of Yersinia pestis genetically distinct from the 14th-century strain or came from pathogens entirely unrelated to bubonic plague. However, further work by the same researchers noted that the spread of several unusual modern variants of plague worldwide can be dated to an evolutionary radiation event approximately coinciding with the Plague of Justinian, supporting the notion that it was caused by a strain of bubonic plague.