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It may have been the most disastrous one-night stand in the history of humanity. Sixty thousand years ago in the Middle East, two humans, slightly different in looks and stature, met and had sex.

As a direct consequence of that liaison between two of our ancestors – one of them a Neanderthal – many of us have a genetic tweak that doubles our risk of severe Covid – leading, scientists estimated, to as many as a million pandemic deaths.

“If this dinner date between the human and the Neanderthal had gone wrong … we would have had hundreds of thousands less deaths,” said James Davies, from the University of Oxford.


Associate Professor Davies, who was part of the team who characterised the genetic consequences of that meeting, described it as the ultimate example of the “butterfly effect”, in which a tiny perturbation can have momentous consequences.

The change was discovered by comparing the genomes of about 2000 people who had suffered from severe Covid with the same number who did not, and looking for common differences. One stood out.

“It’s a single-letter difference out of three billion,” Prof Davies said. “This tiny section of DNA doubles your risk of dying from Covid.”

The physical difference, Prof Davies said, came down to the alignment of a few atoms. “It’s position 45,818,159 on chromosome three, and it’s a single change,” he said. “If you’ve got a G (molecule) at that site, it’s low risk. And if you have an A at that site, it’s high risk.”

Although all Europeans have a small proportion of Neanderthal DNA, the suite of changes accompanying this one crucial tweak show that it must have come from a single encounter that resulted in a single child.

Prof Davies believes that if you have the high-risk variant, a previously understudied gene called LZTFL1 is overactivated. This means that cells in the lungs are slower to launch defences in response to infection, making them more susceptible for longer.

Simon Underdown, a biological anthropologist at Oxford Brookes University, is of the view that this interspecies sex should not be considered so odd.

“We now have much more sensitive reconstructions of the Neanderthals and, arguably, they look just like us,” he said.

Dr Underdown believes they would not even have recognised they were different. They were different enough, however, that 60,000 years on, the genetics sown at that one romantic meeting reaped a pandemic whirlwind.

THE TIMES