5,000-year-old man had the earliest known strain of plague

The oldest strain of Yersinia
pestis–the bacteria behind the plague that caused the Black Death, which
may have killed as much as half of Europe’s population in the 1300s–has been
found in the remains of a 5,000-year-old hunter-gatherer. A genetic analysis
publishing June 29 in the journal Cell Reports reveals that
this ancient strain was likely less contagious and not as deadly as its
medieval version.

“What’s most
astonishing is that we can push back the appearance of Y. pestis 2,000
years farther than previously published studies suggested,” says senior
author Ben Krause-Kyora, head of the aDNA Laboratory at the University of Kiel
in Germany. “It seems that we are really close to the origin of the
bacteria.”

The plague-carrying
hunter-gatherer was a 20- to 30-year old man called “RV 2039.” He was
one of two people whose skeletons were excavated in the late 1800s in a region
called Rinnukalns in present-day Latvia. Soon after, the remains of both
vanished until 2011, when they reappeared as part of German anthropologist Rudolph
Virchow’s collection. After this re-discovery, two more burials were uncovered
from the site for a total of four specimens, likely from the same group of
hunter-fisher-gatherers.

Krause-Kyora and
his team used samples from the teeth and bone of all four hunter-gatherers to
sequence their genomes and then tested them for bacterial and viral pathogens.
They were surprised to find evidence of Y. pestis in RV
2039–and after reconstructing the bacteria’s genome and comparing it to other
ancient strains, the researchers determined that the Y. pestis RV
2039 carried was indeed the oldest strain ever discovered. It was likely part
of a lineage that emerged about 7,000 years ago, only a few hundred years
after Y. pestis split from its predecessor, Yersinia
pseudotuberculosis.

“What’s so
surprising is that we see already in this early strain more or less the
complete genetic set of Y. pestis, and only a few genes are
lacking. But even a small shift in genetic settings can have a dramatic
influence on virulence,” says Krause-Kyora.

In particular, this
ancient strain lacked one crucial thing: the gene that first let fleas act as
vectors to spread the plague. This gene was responsible for efficient
transmission of the bacterium to human hosts, which resulted in the growth of
the infamously grotesque pus-filled buboes in the sick associated with the
medieval bubonic plague. Flea-based transmission also required the death of the
human host, which means that the appearance of the gene could have driven the
evolution of a deadlier disease.

From RV 2039, it
likely took more than a thousand years for Y. pestis to
acquire all the mutations needed for flea-based transmission. And it’s not
clear to what extent RV 2039 experienced the effects of the plague at all.

Y. pestis was found in
his bloodstream, meaning he most likely died from the bacterial
infection–although, the researchers think the course of the disease might have
been fairly slow. They observed that he had a high number of bacteria in his
bloodstream at his time of death, and in previous rodent studies, a high
bacterial load of Y. pestis has been associated with less
aggressive infections. Additionally, the people he was buried near were not
infected and RV 2039 was carefully buried in his grave, which the authors say
also makes a highly contagious respiratory version of the plague less likely.

Instead, this
5,000-year-old strain likely was transmitted directly via a bite from an
infected rodent and probably didn’t spread beyond the infected person.
“Isolated cases of transmission from animals to people could explain the
different social environments where these ancient diseased humans are
discovered. We see it in societies that are herders in the steppe,
hunter-gatherers who are fishing, and in farmer communities–totally different
social settings but always spontaneous occurrence of Y. pestis cases,”
says Krause-Kyora.

These
conclusions–that the early form of Y. pestis likely was a
slow-moving disease and wasn’t very transmissible–challenge many theories about
the development of human civilization in Europe and Asia. For example, some
historians have suggested that infectious diseases like Y. pestis evolved
mostly in megacities of over 10,000 people near the Black Sea. However, 5,000
years ago–the age of RV 2039’s strain–was long before the formation of large
cities. Instead, agriculture was just beginning to appear in Central Europe,
and populations were much sparser.

This timeline, plus
the less contagious and deadly nature of this early Y. pestis strain,
also contradicts the hypothesis that Y. pestis led to the
large population declines in Western Europe at the end of the Neolithic Age.

The authors say
that examining the history of Y. pestis could also potentially
shed light on human genomic history. “Different pathogens and the human
genome have always evolved together. We know Y. pestis most
likely killed half of the European population in a short time frame, so it
should have a big impact on the human genome,” says Krause-Kyora.
“But even before that, we see major turnover in our immune genes at the
end of the Neolithic Age, and it could be that we were seeing a significant
change in the pathogen landscape at that time as well.”

This work was
supported by the Deutsche Forschungsgemeinschaft (DFG, German Research
Foundation) and Germany`s Excellence Strategy. The anthropological and
archaeological research on Ri??ukalns is funded by the DFG and the University
of Latvia.

Cell Reports, Susat et al.: “A 5,000-year-old hunter-gatherer already plagued by Yersinia pestis.” https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00645-8

IMAGE: THIS IMAGE SHOWS THE SKULL BONES
OF THE MAN BURIED IN RI??UKALNS, LATVIA, AROUND 5,000 YEARS AGO. view more 

CREDIT: DOMINIK
GÖLDNER, BGAEU, BERLIN