Genomic Analysis Sets Back Timeline of Plague to Hunter-Gatherer Children in Siberia

Bubonic plague conjures images of wheelbarrows heaped with bodies in the streets of medieval Europe from 1347 to 1352. It’s estimated that 25 to 30 million people died. Fleas and perhaps other insects carried on scurrying brown rats transmitted the infecting bacteria, Yersinia pestis. Mongol traders and fighters had unwittingly brought the scourge from central Asia to the Crimea, traveling through Italy to the rest of Europe aboard ships from the Black Sea.

The infectious disease takes the name Black Death from the black sores, called buboes, that form beneath the skin over swollen lymph nodes. Excruciating joint pain and fever also happen. Bubonic plague kills, often within three days, in up to 75% of cases.

The high mortality rate of the plague rippled through medieval European society for decades, taking two centuries to restore population numbers. Many human settlements were completely abandoned.

The circumstances of the Black Death in Europe led to the idea that human crowding facilitated spread of the infection – it likely did, but the disease did not originate in fourteenth century Europe. A new study, published in Nature, identifies and interprets changes in the pathogen’s genome that point to an earlier presence than the rat-infested, crowded cities of medieval Europe. Genetic evidence, archeological tools, and radiocarbon dating complemented to paint a portrait of an ancient infectious disease that was especially lethal to the young.

Clues in a Cemetery

Ruairidh Macleod, Eske Willerslev, and colleagues at the University of Copenhagen analyzed ancient DNA collected from 42 hunter-gatherer individuals whose remains lay in four cemeteries around Lake Baikal in southeast Siberia. In 18 of the bodies, Y. pestis was the predominant pathogen, reflecting outbreaks from 5520–5265 cal BP and 5315–4235. “Cal BP” is a measurement from geology and archeology that stands for “calibrated years Before Present.” It approximates the calendar age of biological specimens more accurately than does radiocarbon dating, which can fluctuate with climate change.

Comparison of the DNA sequences from exhumed individuals enabled reconstruction of their familial relationships, and the investigators deduced family structures and likely transmission patterns of the infectious disease. But it turns out that bodies discovered together were not genetically related, as might be expected among sick people, but instead may have been left by dying young friends.

The most severe infections were in 8-to-11-year-olds.

“The unusually high number of children and the short timespan was a real puzzle that we’ve been trying to solve since the 1990s. Finding out that plague was the cause is extraordinary, but it makes so much sense,” explained archaeologist Andrzej Weber of the University of Alberta, and principal investigator of the Baikal Archaeology Project.

A Superantigen and Exoneration of Rats

Genome sequencing also revealed a likely mechanism behind the extraordinary lethality of this older plague – genes that encode proteins that function as “superantigens.” These protein toxins rev up the host’s immune response to a devastating level of inflammation. The genome of the more familiar medieval strain of the pathogen doesn’t harbor coding for a superantigen.

“Whether the earliest forms of plague were mild or virulent has been a matter of debate, but our findings demonstrate that these ancient strains were already highly lethal,” said Eske Willerslev. That seems especially so for children, even without flea-borne transmission.

Rats may not have been implicated in these earlier episodes of bubonic plague. Archaeological evidence from marmots near the cemetery site suggests that these large, burrowing mammals may have been part of the transmission train. Marmots carry plague today too, as do prairie dogs, ground squirrels, chipmunks, and wood rats in North America; gerbils, and susliks in Asia; and a variety of rats, mice, and gerbils in Africa and South America. (I’ve had a few of these as pets or rescued them from my cats.)

The new findings “challenge the notion that higher population densities and lifestyle changes during the Neolithic agricultural transition were prerequisites for plague epidemics,” the researchers write.

Together, the findings suggest that the earliest known plague outbreaks may already have been as deadly as later historical forms of the disease, especially for children, even without flea-borne transmission. Perhaps in a broader sense, the findings highlight the incredible adaptability of pathogens to different times and places.