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Ancient DNA shaped our immune system

Posted on behalf of Lee Sweetlove.

Modern humans (Homo sapiens) arose in Africa and migrated to Europe and Asia where they displaced resident archaic humans such as Neanderthals and Denisovans. Sequencing of archaic human genomes shows that interbreeding occurred between these different human species. Now new research shows that interbreeding introduced beneficial immune genes contributing to the hybrid vigour that allowed Homo sapiens to colonise the world.

The work, led by immuno-geneticist Peter Parham at Stanford University School of Medicine, was first reported by Nature after it was presented at a Royal Society symposium in London in June (see ‘Ancient DNA reveals secrets of human history’). Full details of the research are now reported in Science today.

Parham and his team looked at sequence variations in a group of genes encoding a key component of the immune system – the human leukocyte antigens (HLAs) – in Neanderthals, Denisovans and modern humans from around the world.


They found that certain HLA variants from Neanderthals and Denisovans occur in modern humans in Europe and Asia but are absent in the current African population. Because HLA genes evolve rapidly, it is unlikely that these variants pre-date the split between modern and archaic humans but instead are the result of interbreeding between the groups after migration out of Africa.

Parham thinks that most migrating groups of Homo sapiens would have moved out of dire straits by necessity rather than choice.

“By the time they encountered the archaic humans they would have been in bad shape, probably reduced in numbers and suffering from disease.” In contrast, the archaic humans, resident in Eurasia for more than 200,000 years would have been well adapted to local conditions. Interbreeding allowed Homo sapiens to acquire the variants of HLA genes that provide immunity to the pathogens of Europe and Asia.

Some of the HLA variants they gained are involved in innate immunity – the system that allows us to fight off pathogens before disease develops. Parham says that for a hunter-gatherer, “it is much better to get rid of a virus in a few hours than having to get sick while waiting for the adaptive immune system to kick in”.

And these ancient HLA genes are still protecting us today. For example, the archaic HLA-A*11 variant now common in modern Asia provides immunity against some strains of Epstein Barr virus.

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