A single gene shaped the course of the Black Death pandemic

The reduction in copies of a single gene altering the virulence of plague might have resulted in the Black Death.

The Black Death was a pandemic of the disease commonly referred to as plague, which results from an infection of the bacteria Yersinia pestis. Previous research had identified that during pandemics of plague, the bacteria had fewer copies of one gene, pla, compared to normal. Researchers at McMaster University, Canada, and the Institut Pasteur, France, have discovered how this gene's depletion led to pandemic level events, publishing their findings in Science.

'This is one of the first research studies to directly examine changes in an ancient pathogen, one we still see today, in an attempt to understand what drives the virulence, persistence and/or eventual extinction of pandemics,' said Professor Hendrik Poinar, senior author of the study and director of the McMaster Ancient DNA Centre.

There are two main forms of plague: bubonic (the most common form) and pneumonic. Another form, septicemic plague, is often a complication of bubonic or pneumonic plague.

The researchers used ancient DNA recovered from bones of people buried in medieval cemeteries in London and Denmark that had died from plague. They compared this data to DNA collected from current day plague patients and found that there were fewer copies of the pla gene in the ancient DNA samples.

The researchers replicated these levels of pla in Y. pestis in the lab. Then, using mouse models of bubonic, pneumonic and septicemic plague, infected the mice with the bacteria. They found that depletion of pla made the infection less deadly in bubonic models of plague (but not pneumonic or septicemic models), through reduced virulence, which is the bacteria's ability to harm its host.

'The reduction of pla may reflect the changing size and density of rodent and human populations,' said Professor Poinar. 'It's important to remember that plague was an epidemic of rats, which were the drivers of epidemics and pandemics. Humans were accidental victims.'

Y. pestis is spread from the bites of infected fleas, direct contact with infected tissues, and inhalation of infected respiratory droplets. The researchers hypothesised that in the 14th century before the Black Death pandemic, plague bacteria with normal amounts of pla would have killed large amounts of rats, allowing for selection of the depleted pla variant in surviving urban rats. The longer time to death due to the pla depletion would have allowed rats to carry the fleas, and the disease, to more locations which spread plague into more people's homes and caused the Black Death pandemic.

'Although our research sheds light on an interesting pattern in the evolutionary history of plague, the majority of strains which continue to circulate today in Africa, South America and India are the more virulent ones, the ones that were previously responsible for massive mortality,' said Ravneet Sidhu, a PhD student at McMaster University and first author of the study.

The pla depleted strains of Y. pestis are not seen today, believed to be due to an 'epidemic burnout' where the strain would have become extinct after the Black Plague pandemic. However, the wild type would have still been circulating in wild rat populations outside of cities, allowing the disease to persist into modern times.