[Série] “The missing genome”: pathogens from beyond the grave

Ancient DNA reveals well-kept secrets about the migrations, evolution and interbreeding of human populations, but also about the history of pathogens and animals. Second article in a series on the bubbling science that is paleogenomics.

The scene takes place at the beginning of the XIIIe century on the territory of the Byzantine Empire, more precisely in Troy, in present-day Turkey. A pregnant woman, about 30 years old, gives birth to a baby boy. This new mother, however, is ill; she suffers from a high fever. She does not survive the delivery, just like her baby, also affected by the infection, who dies before even being born.

Stories like this, humanity has known since the dawn of time. What disease took away these two lives? Thanks to science, this little Trojan tragedy is now the subject of an unprecedented understanding. The example illustrates the power of paleogenomics to rewrite the history of pathogens. A story inextricably linked to ours.

“Ancient DNA opens a window to a completely unexplored past, for which we have no historical records. Otherwise, you can’t look at a bone and know that the person it belonged to died of a bone infection. E.colifor example — it’s just impossible,” says Hendrik Poinar, director of the Center for Ancient DNA at McMaster University in Hamilton, Ontario, in awe.

In 2017, Professor Poinar and his colleagues published an article describing in detail the sad fate of the Trojan mother, who until then had been a mere skeleton. They got there because the bones of the deceased had two small calcified nodules—abscesses, probably—rich in organic matter.

Analyzes revealed the presence of the DNA of the woman, of her fetus, but also of two bacteria: one typical of infections linked to pregnancy (Gardnerella vaginalis), the other more associated with urinary tract infections (Staphylococcus saprophyticus). The genome of the second bacterium differs considerably from the strain of S. saprophyticus that circulates in humans today, but approximates that affecting livestock. Scientists have thus deduced that this bacterium had one day “jumped” from cows to humans.

“All of these discoveries come from a very small sample of one cubic centimeter,” says Poinar. Without these methods, we would never have had this kind of information about women’s health at that time. I think it’s really cool. Only a handful of laboratories in the world know how to conduct such experiments.

Bestiary of Pathogens

Cholera, malaria, E.coli : numerous pathogenic agents in recent years have revealed their secrets to geneticists who know how to decipher their DNA.

The latest example to date: a team based at the Max-Planck Institute for Evolutionary Anthropology, in Leipzig, proposed in an article published in mid-June in Nature a geographical and temporal origin to the bacterium Yersinia pestisresponsible for the Black Death, which took half of the European population to the afterlife in the XIVe century.

The research team analyzed the DNA of teeth found in a cemetery in Kyrgyzstan. The tombs – dated 1338 and 1339, seven and eight years before the arrival of the Black Death in Europe – indicate in Syriac that the victims were carried away by the “pestilence”. The genetic material of Yersinia pestis preserved in their teeth turns out to be the basis of the different strains that subsequently emerged. Logical conclusion: this is where the genesis of the terrible pandemic of the Middle Ages is found.

Diseases like the Black Death have had a profound impact on human evolution. Hendrik Poinar is also taking part in a major research project, the results of which are about to be published, which shows which human genes have been favored or disadvantaged by Yersinia pestis. The team compared the genomes of dead individuals before, during and after the terrible episode of the XIVe century.

A similar study, but concerning tuberculosis, was published in 2021 by the team of Franco-Spanish geneticist Lluis Quintana-Murci. These scientists showed that a genetic mutation predisposing humans to tuberculosis had considerably decreased in frequency (from 10% to 2-4%) in the space of two millennia in Europe. A very strong natural selection pressure is involved, they say.

Smallpox and vaccinia

Marie-Hélène B.-Hardy, a Quebec doctoral student working in Professor Poinar’s laboratory, is studying smallpox epidemics in North America in the 1800s.e and XIXe centuries. “We are looking at the interrelation between the evolution of this virus and the evolution of public health policies”, explains the one who joined this internationally renowned team four years ago.

To do this, it relies on two major collections of human remains from Montreal and Philadelphia. The skeletons were recovered mainly during “rescue excavations”, organized for example on the sidelines of an excavation made necessary by a construction site.

In some cases—like when the coffins are painted red—archaeologists are pretty sure it was the smallpox that killed. But most of the time, they have to cross their fingers to find the infamous virus that causes it. And if they can’t find it, that doesn’t mean there wasn’t. “With ancient DNA, absence of evidence is not evidence of absence,” says M.me B.-Hardy.

For the moment, the doctoral student has not found any genetic trace of smallpox in her samples, but remains hopeful. The characterization of a few strains would allow him to understand how the disease landed in North American cities: by sea or by inland trade routes? It also analyzes the historical strains of vaccinia (responsible for “cowpox”), which were used in the XVIIIe and XIXe centuries to immunize populations.

From the plague to small colds

Paleogenomics helps to better understand diseases of historical significance, such as smallpox — which decimated Native American populations when Europeans arrived — and the Black Death, but Poinar also hopes the scientific community will benefit from this powerful science to probe the history of harmless diseases.

“What interests me a lot, he says, is the burden imposed by diseases for which we have no historical records. We already know how terrible the plague was. However, we know next to nothing about common pathogens that have affected humans on a very large scale; yet these are probably responsible for the majority of deaths in history. »

“I’m not claiming ancient DNA is the only way to uncover the past,” he continues, “but I think it’s a particularly powerful tool for uncovering which bugs sickened humanity and what their genome was.” We can even test the virulence and toxicity of the genome of these pathogens in the laboratory. Understanding their evolutionary trajectory helps us know what the future holds. »

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