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Bubonic Plague gene study shows why many people many died

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Scientists, researchers, and academia remain at the forefront of human progress. People benefits because of their work and studies. For instance, their work and inferences from carbon dating and DNA analysis have enabled humans to learn from history and adapt to time present.


A group scientists raised the research benchmark further this week. They studied centuries-old DNA (Deoxyribo Nucleic Acid) of victims and survivors of the Bubonic Plague or Black Death pandemic. The deadly plague spread through Europe, Asia, and Africa. Spread by fleas, the plague killed around 200 million people in the 14th century.


Their study shows why many people succumbed to the plague and many survived. The clue is genetic differences. They show how human immunity continues to evolve since that terrifying era.


Researchers from McMaster University, the University of Chicago, the Pasteur Institute, and others studied and identified genes that protected many people from the plague. The journal Nature published their study earlier this week.


McMaster University, Hamilton, Ontario, Ancient DNA Centre Director Hendrik Poinar wrote the paper published by Nature. Evolutionary Geneticist Poinar is principal investigator with the Michael G DeGroote Institute for Infectious Disease Research and McMaster's Global Nexus for Pandemics & Biological Threats.


One inference of the group’s study should alarm the world that continues to suffer Covid-19 pandemic and variants of the virus. The same gene that once offered immunity against the Bubonic Plague show increased susceptibility to autoimmune diseases such as Crohn's and rheumatoid arthritis, says the researchers’ report.


The researchers’ study focused on a 100-year window before, during and after the plague that reached London in the mid-1300s. Bubonic Plague, caused by the bacterium Yersinia pestis, remains the single greatest human mortality event in recorded history. The plague killed more than 50 per cent of the people Europe, Asia, and Africa.


The experts extracted more than 500 old DNA samples from the remains of people who died before the plague, died because of it, or survived in London, including individuals buried in the East Smithfield plague pits used for mass burials in 1348-9. They took more DNA samples from the remains buried in five other locations across Denmark.


The scientists looked for signs of genetic adaptation related to the plague. They identified four genes. These genes help produce proteins that defend humans from invading pathogens. They found that versions of those genes, called alleles, either protected or made one susceptible to the plague.


People with two identical copies of a particular gene, known as ERAP2, survived the plague at much higher rates than those with the opposing set of copies, because the 'good' copies allowed for more efficient neutralisation of Y pestis bacteria by immune cells.


“When a pandemic of this nature that kills 30 to 50 per cent of the population occurs, there is bound to be selection for protective alleles in humans,” says Poinar. “This means people susceptible to the circulating pathogen will succumb. Even a slight advantage means the difference between surviving or passing away. Survivors of breeding age will pass on their genes.”


Herd immunity builds after the first flush of viral attack, we know. Europeans were susceptible to Bubonic Plague because they had no previous exposure to Yersinia pestis. Mortality rates decreased after repeated waves of the pandemic over centuries.


Researchers estimate that people with the ERAP2 protective allele (the good copy of the gene, or trait), were 40 to 50 per cent more likely to survive than those who did not.


One of the paper authors, University of Chicago Genetic Medicine Professor Luis Barreiro says, “The selective advantage associated with the selected loci are among the strongest ever reported in humans showing how a single pathogen can have such a strong impact to the evolution of human immunity.”


Human immunity has evolved to respond in different ways to pathogens. Once a protective gene against the plague, today has increased susceptibility to autoimmune diseases. Evolution plays this balancing act with our genome, the paper says.


“Understanding the dynamics that have shaped human immunity helps understand how past pandemics, like the plague, contribute to our susceptibility to disease in modern times,” concludes Poinar.


Sudeep Sonawane, an India-based journalist, has worked in five countries in the Middle East and Asia. Email: sudeep.sonawane@gmail.com


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