The Black Dying could have formed the evolution of immunity genes

Scientists at the Institut Pasteur, McMaster University and the University of Chicago have identified protective genes against the devastating bubonic plague pandemic that raged across Europe, Asia and Africa nearly 700 years ago. These genes that once conferred protection against the Black Death are now today associated with an increased susceptibility to autoimmune diseases.

The epidemic known as the “Black Death” that raged in the Middle Ages remains the deadliest event in all of human history, responsible for the death of a large part of the population in some of the most densely populated regions of the world at the time.

When a pandemic of this magnitude – killing 30 to 50% of the population – occurs, there is necessarily selection in favor of protective alleles in humans, which implies that people susceptible to the circulating pathogen will die. The smallest selective advantage will make the difference between survival or death. Of course, survivors of childbearing age will pass on their genes explains evolutionary genetics biologist Hendrik Poinar, co-last author of the study, director of the Center for Ancient DNA at McMaster University.

The pathogen responsible for Black Plague it’s the bacteria Yersinia pestis. ” The plague bacillus, is one of the most virulent infectious agents on Earth’s surface. We are interested in understanding the molecular mechanisms of pathogenicity of this microorganism, as well as the immune responses that are triggered after infection by this bacterium in humans comments Javier Pizarro-Cerdá, co-author of the study, director of the research unit Yersinia at the Institut Pasteur, director of the Collaborating Center ‘Prague’ of the World Health Organization and deputy director of the National Reference Center ‘Pest and other Yersiniasis’.

The researchers wanted to understand whether in the Middle Ages the plague bacillus would have selected protective genes against the bubonic plague in humans. So they analyzed ancient DNA samples taken from the remains of individuals who died before, during or after the Black Death in London, where several particularly well-preserved and well-dated cemeteries are present. Other samples were taken from human remains in five cemeteries in Denmark. By comparing the DNA of victims and survivors of the Black Death pandemic that dates back centuries, scientists have identified key genetic differences that explain the survival or death of sufferers and the evolution of our immune system since then.

The Black Death may have shaped the evolution of immunity genes, determining our current response to autoimmune diseases

Four selectable genes were identified, all involved in the production of proteins that defend our systems against pathogens. The researchers found that versions of these genes, called alleles, conferred protection or susceptibility to the disease. A markedly higher survival rate was observed for individuals carrying two identical copies of a particular gene, called ERAP2, compared to those with different alleles. Scientists estimate that people who carry the protective allele of the ERAP2 gene (the “good” copy of the gene) had a 40 to 50 percent better chance of survival than others.

This genetic variability still exists in our genomes today. ” Few teams in the world are able to study the interactions between immune cells and bacteria. Y. pestis. Our experience allowed us to show the real effect of the ERAP2-related phenotype on the response to a live plague bacterium explains Christian Demeure, researcher at the unit Yersinia at the Pasteur Institute.

Using human cells, scientists studied the interaction between the bacterium Y. pestis and immune cells based on their ERAP2 alleles. They analyzed how macrophages neutralized the bacteria Y. pestis. ” The results were categorical. The “good” copies of the ERAP2 gene allowed a more efficient neutralization of Y. pestis by immune cells. Having the correct version of ERAP2 appears to have been key for immune cells to be able to destroy bacteria. Yersinia pestis”, comments Christian Demeure.

“The selective advantage associated with selected loci is one of the strongest ever reported in humans, which demonstrates the importance of the impact that a single pathogen can have on the evolution of the immune system. says geneticist Luis Barreiro, co-author of the study and professor of genetic medicine at the University of Chicago.

According to scientists, these genes that once provided protection against the Black Death are now associated with increased susceptibility to autoimmune diseases such as Crohn’s disease and rheumatoid arthritis. This is the balancing act that evolution plays with our genome.

The identification of ERAP2 reinforces the idea that what allows survival in one era can alter survival in another.. concludes Javier Pizarro-Cerda.

The results of the study, the fruit of years of work by doctoral student Jennifer Klunk, who worked for the Ancient DNA Center at McMaster University, postdoctoral fellow Tauras Vigylas, at the University of Chicago, in association with the Institut Pasteur’s Yersinia Research Institute, offered unprecedented insight into the immune genes of victims of the Black Death and their interaction with Y. pestis in current human populations.

Their study was published on 19 October 2022in the magazine Nature.

The evolution of immune genes is associated with the Black Death, NatureOctober 19, 2022

Jennifer Klunk1,2*, Tauras P. Vilgalys3*, Christian E. Demeure4, Xiaoheng Cheng5, Mari Shiratori3, Julien Madej4, Rémi Beau4, Derek Elli6, Maria I. Patino3, Rebecca Redfern7, Sharon

  1. DeWitte8, Julia A. Gamble9, Jesper L. Boldsen10, Ann Carmichael11, Nukhet Varlik12, Katherine Eaton1, Jean-Christophe Grenier13, G. Brian Golding1, Alison Devault2, Jean-Marie Rouillard2,14, Vania Yotova15, Renata Sindeaux15, Chun Jimmie Ye16 , 17, Matin Bikaran16, 17, Anne Dumaine3, Jessica F Brinkworth18,19, Dominique Missiakas6, Guy A. Rouleau20, Matthias Steinrücken5,21, Javier Pizarro-Cerdá4, Hendrik N. Poinar1,22,23,#, Luis B. Barreiro3 ,21,24,25,#

*These authors contributed equally to this work and are presented in alphabetical order #These authors jointly supervised this work

  • McMaster Ancient DNA Centre, Departments of Anthropology, Biology and Biochemistry, McMaster University, Hamilton, Ontario, Canada L8S4L9
  • Daicel Arbor Biosciences, Ann Arbor, MI, USA
  • Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA 4 Yersinia Research Unit, Institut Pasteur, Paris, France
  • Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
  • Department of Microbiology, Ricketts Laboratory, University of Chicago, Lemont, IL, USA 7 Center for Human Bioarchaeology, Museum of London, London, UK, EC2Y 5HN
  • Department of Anthropology, University of South Carolina, Columbia, SC, USA
  • Department of Anthropology, University of Manitoba, Winnipeg, Manitoba, R3T2N2
  • Department of Forensic Medicine, Anthropology Unit (ADBOU), University of Southern Denmark, Odense S, 5260, Denmark
  • Department of History, Indiana University, Bloomington, IN, USA 12 Department of History, Rutgers University-Newark, NJ, USA

13 Montreal Heart Institute, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada, 31 H1T 1C7 14 Department of Chemical Engineering, University of Michigan Ann Arbor, Ann Arbor, MI, USA

  • Sainte-Justine University Hospital Center, Montreal, Quebec, Canada, H3T 1C5
  • Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, 17 Institute for Human Genetics, University of California, San Francisco, CA, USA
  • Department of Anthropology, University of Illinois Urbana-Champaign, Urbana, IL, USA
  • Carl R Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA 20 Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada, H3A 2B4
  • Department of Human Genetics, University of Chicago, Chicago, IL, USA
  • Michael DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada L8S4L9
  • Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Canada 24 Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA 25 Committee on Immunology, University of Chicago, Chicago, IL, USA

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