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1,500-year-old plague victims shed light on disease origins


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Scientists have sequenced the genome of the pathogen that caused one of the most devastating plagues in human history, shedding light on where the disease came from and how it spread.

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Skeletal remains of plague victims in Bavaria, Germany. Photograph: McMaster University, Canada

The Plague of Justinian occurred in the sixth century AD and resulted in over 100 million deaths by some estimates. Named after the Byzantine emperor Justinian I, the outbreak was one of the first recorded plague pandemics.

Scientists have previously analysed DNA samples taken from plague victims to determine that the Plague of Justinian was likely caused by Yersinia pestis, the bacterium also responsible for the Black Death.

In a new study appearing in Lancet Infectious Diseases, researchers built on this previous work and sampled DNA from the teeth of 1,500-year-old plague victims in Bavaria.

They then screened the samples for Y pestis DNA and sequenced the genomes of the two strains they found.

Professor Edward Holmes, from the University of Sydney, was one of the authors of the study, and said it was the oldest pathogen ever sequenced.

"This is the first complete genome from one of the most significant disease events in human history," he said.

The results showed the strains from the plague victims were distinct from those involved in the Black Death, the later pandemic which killed an estimated 60% of the European population.

The Justinianic strains appear to be an evolutionary “dead end” when compared with modern strains, and most likely originated from Asia and then spread to Europe along trade routes such as the Silk Road.

Associate professor Jeremy Austin, from the Australian Centre for Ancient DNA said the study was an important insight into the evolution of an infectious disease.

"It certainly tells us that these catastrophic diseases aren't things that evolve once, and then lurk around waiting for an opportunity to reappear – they actually evolve multiple times from different ancestors," he
said.

"Which makes it very much harder to predict when they're going to happen next, and how they evolve and therefore how you might prevent them happening."

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A plague victim's tooth from which DNA was extracted. Photograph: McMaster University, Canada

Allen Cheng, associate professor at Monash University's Infectious Diseases Epidemiology unit, said the Lancet study was "fascinating".

"This is a great example of what can be done with all this new sequencing technology," he said.

"There's a whole field of paleo-phylogeny, going back into history and trying to work out the origin of diseases.

"It also illustrates a really interesting point: really dangerous bugs like plague that kill their hosts, aren't very evolutionarily successful. And that's a pattern we see with a lot of other bugs as well."

Holmes said one of their objectives was to determine why the Justinianic plague was so severe.

"Plague is still around today in parts of the world, and is associated with much lower death rates than it was in the past," he said.

"Was there something about the genome of these ancient pathogens that made them especially virulent, or was it the way that people lived in the past, conditions were not so good, general health wasn't as good, that
made them die in higher numbers?"

Holmes said there were some "hints" of gene mutations affecting virulence in the Justinianic strains, but more work would be required to confirm any specific mechanisms.

He said the paper was indicative of technical advances that have revolutionised the study of ancient DNA.

"Modern technology has made [studying] ancient DNA a much stronger science," he said.

DNA is prone to degradation over time into small fragments, which was an issue for older sequencing techniques that relied on getting comparatively long, coherent strands of DNA. However, "next gen" sequencing is designed to use many small pieces of DNA, and so has made sequencing older DNA much easier.

"We can amplify huge numbers of these small fragments, and basically glue them together," Holmes said.

Austin agreed, saying new techniques had resulted in boom of genome sequences from ancient animals, humans, and other organisms.

"Ten years ago, everyone was saying we're not going to be able to sequence genomes of extinct anything, whether they be humans, animals, plants or other things lurking around in the environment," he said.

"We're certain using these techniques to get access to information that even five years ago we never thought was possible."

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Interesting and kinda scary, I always thought that since all our ancestors were plague survivors, we must have evolved some kind of some natural resistance against the plague

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Interesting and kinda scary, I always thought that since all our ancestors were plague survivors, we must have evolved some kind of some natural resistance against the plague

that is just not the way it works

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  • 2 weeks later...

Interesting and kinda scary, I always thought that since all our ancestors were plague survivors, we must have evolved some kind of some natural resistance against the plague

that is just not the way it works

It is one possible mechanism but apparently the virulence of pathogens can change too

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