Celebrating differences. migration of the Gypsies in India 1000 years ago ( see map ) set the stage for a revealing study of how diseases can influence the genome
( Top) Corbis. (Bottom) Mr. Netea AND al./Proceedings of the National Academy of Sciences
The Black Death not only destroy millions of Europeans during the 14th century. He left a mark on the human genome, favoring those who carried certain genes of the immune system, according to a new study. These changes may help explain why the Europeans react differently than others to certain diseases and have different sensitivities to autoimmune disorders.
geneticists know that human populations are changing the face of illness. Some versions of our genes help us fight against infection better than others, and people who carry these genes tend to have more children than those who do not. Thus, the beneficial genetic versions persist, while other versions tend to disappear as those who wear them die. This weeding out all but the best genes is called positive selection. But researchers are struggling to identify positively selected genes in humans, as many genes vary from one individual to another.
Enter Mihai Netea, an immunologist at the Radboud University Nijmegen Medical Centre in the Netherlands. He realized that in his home country, Romania, the existence of two distinct ethnic groups the opportunity to see the hand of natural selection in the human genome. There are a thousand years, the people-commonly known as gypsies-Rroma migrated to the north of India Europe. But they married little with European Romanians and therefore very distinct genetic origins. Yet, living in the same place, both groups had the same conditions, including the Black Death, which has not reached the northern India. Thus, the researchers looked for genes favored by natural selection by searching for similarities in the European Roma and Romanians are not found among North Indians
Netea. Jaume Bertranpetit evolutionary biologist of the University Pompeu Fabra in Barcelona, Spain; and their colleagues searched for differences to more than 196,000 places in the genomes of 100 Romanians from Europe and 100 Rroma. For comparison, the researchers also cataloged the differences 500 people living in the northwest of India, where the Rroma came. They then analyzed the genes that changed the most to see which were most favored by selection.
genetically, Rroma are still quite similar to the Northwest Indians, although they have lived side by side with the Romanians for a millennium, the team found. But there were 20 genes in the Rroma and Romanians who had changes that are not visible in the Indian versions of these genes Netea and colleagues report online today in the Proceedings of the national Academy of sciences . These genes "have been positively selected for Romanians and Gypsies, but not for Indians," says Netea. "It is a very strong signal."
These genes included one for the pigmentation of the skin, the one involved in inflammation, and that associated with susceptibility to autoimmune diseases such as rheumatoid arthritis. But those Netea and Bertranpetit were most excited were a group of three immune system genes found on chromosome 4. This gene codes for Toll-like receptors, proteins that cling to harmful bacteria in the body and launches a defensive response . "We knew they must be important for host defense," said Netea.
What events in history may have favored these versions of genes in Roma and Romanians but not among the Indians? Netea and his colleagues tested the ability of Toll-like receptors to react to Yersinia pestis , the bacterium that caused the black death. They found that the strength of the immune response varied according to the exact sequence of Toll-like receptor genes.
Netea and Bertranpetit propose that the Roma and European Romanians came to have the same versions of these genes of the immune system due to pressure evolution Y. pestis . other Europeans, whose ancestors also faced and survived the black Death, made similar changes in the genes of Toll-like receptors. But the people of the China and Africa and two other locations, the black death has not reached, do not have these changes. (There were multiple plagues throughout history worldwide, but none were as deadly as the Black Death, which killed about one in four Europeans, and thus exerted strong selection.) The similarities in other genes were probably caused by other conditions experienced by the Roma and the Europeans, but not the Indians.
"the use of two people living in the same geographical area is very smart," says geneticist human population Oscar Lao Erasmus MC in Rotterdam, the Netherlands, who was not involved in the study. "This experimental evidence is very important," he added. It shows that the plague bacterium interacts effect with the proteins encoded by genes favored by natural selection. "This should be the goal of all these types of analyzes."
"There is a beautiful hypothesis they put forward," agrees Lluis Quintana-Murci, the human population geneticist at the Pasteur Institute in Paris, who was not involved in the study. Genetic changes can have modern effects. "The presence of these particular versions of these genes may provide the basis of evolution to explain why some people are more at risk" for certain types of disease, said Douglas Golenbock, an immunologist at the University of Massachusetts Medical School in Worcester " The side effect. seems that Europeans have a proinflammatory immune system than those who have never experienced the black death. "
However, Lao and Quintana-Murci ask whether the convergence of these genes could be explained another way. It is possible that these favorable versions were introduced in the Rroma by crossing between Rroma and the Romanians, they suggest. additional sequencing convergent genetic regions should answer this question, said Quintana-Murci. It is also important to check how these toll-like receptors respond to other deadly bacteria to see if other diseases could have been the cause of change. This is likely to happen, Quintana-Murci added. "This will inspire other laboratories to see if other bacterial infections could also explain the [selection] ".
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