Neanderthal DNA contributes to immune response differences among populations
Two gene-expression studies could explain why people of African descent respond more strongly to infection, and are more prone to autoimmune diseases.
It's long been clear that people from different geographic locations of the world differ in their susceptibility to developing infections as well as chronic inflammatory and autoimmune diseases. Now, two studies reported in Cell on October 20 show that those differences in disease susceptibility can be traced in large part to differences at the genetic level directing the way the immune systems of people with European and African ancestry are put together.
The researchers also found that differences between populations have been selected for over time because they conferred advantages to people facing distinct health challenges in the places where they lived. As a result, people of African ancestry generally show stronger immune responses than Europeans do as the European populations have been selected to display reduced immune responses since our ancestors first made their way out of Africa. Intriguingly, the immune systems of Europeans were partly shaped by the introduction of new genetic variants through interbreeding between some of our early European ancestors and Neanderthals. The findings might also offer insight into why people of African descent are more prone to autoimmune diseases caused by an overactive immune system.
In one study, geneticist Luis Barreiro of the University of Montreal in Canada and his colleagues collected blood samples from 80 African Americans and 95 people of European descent. From each sample, they isolated a type of immune cell called macrophages, which engulf and destroy bacteria, and infected each culture with two types of bacteria and measured how the cells responded. Macrophages from African Americans, they found, killed the bacteria three times faster than those of European Americans. A measurement of gene expression level change in response to the infection reveals that around 30% of the approximately 12,000 genes expressed differently between the two groups, even before infection. And many of the genes whose activity changed the most during the immune reaction had sequences that were very similar between Europeans and Neanderthals, but not Africans.
In the second study, population geneticist Lluis Quintana-Murci and his colleagues at the Pasteur Institute in Paris collected samples from 200 people living in Belgium with 50% of them being African descent and the other half European descent. The researchers tested a different type of immune cells called monocytes and infected them with bacteria and viruses. Once again, the two groups showed differences in the activity of numerous genes, and Neanderthal-like gene variants in the European group played a major role in altering their immune response. The differences were especially stark in the way that the two groups responded to viral infection.
The two studies made strikingly similar findings despite the fact that they focused on different types of immune cells. According to the researchers, more work is now needed to better understand the role of environmental and other factors, including epigenetic changes, in the differences they've observed.
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