It’s well known that people from different parts of the world vary in their susceptibility to developing infections and diseases.
But two new studies show these differences are genetic and can be traced back all the way to the Neanderthals, who died out some 40,000 years ago.
One study suggests Americans of African descent have a stronger immune response to infection compared to Americans of European descent.
Researchers from the Institut Pasteur and CNRS in Paris, France found that genetic differences between populations confer advantages, depending on the environment where those people are living.
As a result, according to the new evidence in another study, people of African ancestry generally show stronger immune responses than Europeans do.
The French study suggests that European populations have displayed reduced immune responses since our ancestors first made their way out of Africa.
And intriguingly, the immune systems of Europeans were partly shaped by the introduction of new genetic variants through interbreeding between early European ancestors and Neanderthals.
‘Our findings show that population differences in transcriptional responses to immune activation are widespread, and that they are mainly accounted for by genetic variants that differ in their frequencies between human populations,’ said Lluis Quintana-Murci of Institut Pasteur and CNRS in Paris.
He and his colleagues used RNA-sequencing to describe the way that immune cells, called monocytes, derived from 200 people of self-reported African or European ancestry would respond to attack by a bacteria or a virus.
They detected many differences in the activity of particular genes in those immune cells both within and between populations.
They discovered that changes in a single gene encoding an important immune receptor lead to decreased inflammation only in Europeans.
The team found strong evidence of selection on genes that control the immune response and that Europeans ‘borrowed’ some key regulatory variants from Neanderthals.
These variants affect the way their immune systems respond to viral challenges, giving them a lower response to infection than those of African descent.
Luis Barreiro of the University of Montreal and the CHU Sainte-Justine in Canada, commented: ‘I was expecting to see ancestry-associated differences in immune response but not such a clear trend towards an overall stronger response to infection among individuals of African descent.’
He and his colleagues took a similar approach to test for the effects of African versus European ancestry on changes in the activity of immune cells in the other study.
His group focused on another type of immune cell known as primary macrophages and their response to live bacterial pathogens.
In their experiment, the experts infected macrophages derived from 80 African and 95 European individuals with either Listeria or Salmonella to look for differences in response and work out how whether there was a link with their ancestry.
They identified thousands of genes showing population differences in how information in a strand of DNA is copied into a new molecule of messenger RNA, in response to infection.
They also found that African ancestry is associated with a stronger inflammatory response, which limited the growth of bacteria.
But Professor Barreiro was careful not to qualify it as better: ‘The immune system of African Americans responds differently, but we cannot conclude that it is better, since a stronger immune response also has negative effects, including greater susceptibility to autoimmune inflammatory diseases such as Crohn’s disease.
‘Too much inflammation can damage organs and leave sequelae [the after effects of a disease].
‘In short, a strong immune response can be beneficial in some areas but a disadvantage in others.’
The researchers also observed the signature of past selection on certain genes, adding weight to the idea that genetic variants were passed on to modern humans from Neanderthals.
Dr Barreiro added: ‘The genetic and molecular basis of ancestry-related differences in disease susceptibility has been a mystery.
‘These results provide a first description of differences in immune response and associated genetic basis that might explain differences in susceptibility to disease between people of African and European ancestry.
‘More generally, our results demonstrate how historical selective events continue to shape human phenotypic diversity today, including for traits that are key to controlling infection.’
The researchers noted that the two studies made strikingly similar findings despite focusing on different types of immune cells.
However, they believe more work is needed to better understand the role of environmental factors.
By: Sarah Griffiths
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