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The Black Death Reshaped the Human Genome

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Lisa Winter

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295 The Black Death Reshaped the Human Genome
CDC

The Black Death, one of the most lethal pandemics humans have ever encountered, did not affect everyone equally. Those with certain variations of genes for the immune system were spared from contracting the plague while others with different variations died from the disease very quickly. Due to the sheer amount of people lost to the disease, those certain genetic variations were strongly advantageous and has had an impact on subsequent generations. This research comes from lead author Hafid Laayouni from the Universitat Pompeu Fabra in Spain and was published in the Proceedings of the National Academy of Sciences

The Black Death originated in Asia and was brought to Europe along silk trade routes in the 1340s. It had widespread devastating effects, killing 1.5 million people in the first two years. By the end of the century, the world’s population had dropped from 450 million to 350 million. The Black Death was caused by the plague, a fatal disease brought about by the bacteria Yersinia pestis. It was transmitted by fleas that were carried on rats and other animals that were commonly in close contact with humans. While the plague can now easily be controlled with antibiotics, there was no knowledge of any of these concepts in the 14th century.

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Geneticists realized that the plague did not have universal effects because some people had certain genetic mutations which gave an incredible immunological advantage. In the face of the Black Death, those without the mutations died out while those with the mutation lived and continued to reproduce (this is basically “winning” at evolution). This is a textbook example of positive selection, though the exact genes responsible had never before been determined. 

In order to identify the genes responsible for this benefit, immunologists, biologists, and epidemiologists gathered information from a variety of populations that have fairly reproductively isolated. Several hundred years before the onset of the Black Death, a group of gypsies migrated away from Northern India and into Romania. Though they did not breed very often with the Europeans and were genetically isolated, they were exposed to all of the same environmental factors of the Black Death. Thus, it stood to reason that the gypsies and European Romanians would have a higher concentration of the beneficial gene variant than those from the gypsies’ former home of Northern India, where the plague did not reach.

Researchers collected DNA samples from 500 people from each group (gypsies, Romanians and Northern Indians) and compared 196,000 loci to see which genes were most affected by the plague’s selective pressure. The gypsies should have been more genetically similar to the Northern Indians than the Romanians, making any plague-influenced variations obvious. Ultimately, there were a total of twenty genes that were much different in the gypsies and Romanians than the Northern Indians. 

The researchers hit pay dirt when they discovered many of the variations were on a cluster of genes that code for toll-like receptors, which help the body latch on and eliminate bacterial contaminants. After hundreds of years of intermittent plague outbreaks, the increased immune response variants were very strongly selected for in the gypsies and European Romanians. The variations were found in some Northern Indians, but has been a fairly neutral mutation thus far, since that population has never been subjected to such intense selective pressure. While it has not been completely ruled out that interbreeding between the gypsies and Romanians may have played a role in this shared variation, the researchers don’t believe this is the case.

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The same genes that benefitted their ancestors during bouts of the plague may influence their interaction with modern diseases, as those with European ancestry have higher instances of inflammatory disorders (caused by an overactive immune system) than those whose lineage was not affected by the plague. Next steps of the research will investigate how these genes respond to other disease-causing bacteria to see if the selective pressure of the Black Death really was the cause for the genetic convergence.


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