Once upon a time, prehistoric humans and our ancient Neanderthal cousins met and procreated. Except, that ‘once upon a time’ meeting is now looking less like a one night stand and more like a protracted bonkfest, according to a new analysis of modern human ancestry.

When anatomically modern humans traipsed out of Africa into Europe some 75,000 years ago, they headed into territory occupied by Neanderthals. For over 30,000 years, until the latter died out, the two species lived side by side through much of Eurasia.

In 2010, publication of a Neanderthal genome revealed that early humans shared more than just geography with the species.

Scattered throughout the genome of anyone with non-African heritage are chunks of Neanderthal DNA – the hallmarks of a prehistoric tryst between our closest hominin relatives.

The presence of these chunks, making up 2%, on average, of the genome of anyone with roots in Europe, Asia, Australia or the Americas, pointed to a single period of intermingling – probably 50,000 to 60,000 years ago – not long after Homo sapiens emerged from Africa.

But that simple story was complicated by the discovery that people in East Asia have up to 20% higher Neanderthal ancestry than present-day Europeans.

“There was some debate about, okay, is this just random, or is it meaningful in any way?” says Josh Schraiber from Temple University in Philadelphia, US.

One of the biggest debates, says Schraiber, pits two competing theories against each other. The first is that the Neanderthal bits in Europeans have gradually been diluted through mixing with human populations that didn’t breed with Neanderthals.

The second theory suggests that multiple periods of interbreeding – or admixing – in Europe and Asia have resulted in the differing rates of Neanderthal ancestry.

Evidence for multiple matings already exists, in the form of a 40,000 year old human fossil from Romania with a recent Neanderthal ancestor, whose Neanderthal DNA nonetheless did not become part of modern-day human genomes.

“If it happened there,” says Schraiber, “why wouldn’t it be happening in other places?”

To find out which scenario – dilution or multiple matings – was more likely, he and his colleague Fernando Villanea first looked at European and Asian populations separately. They analysed the distribution of Neanderthal chunks across genomes in the 1000 Genomes Project, a large public database of human genetic variation.

In both Europe and Asia, the patterns of inheritance pointed to multiple periods of mating, rather than just one.

But they couldn’t be sure that dilution didn’t also play a part.

To answer the this question, they would need to compare Europeans and Asians, a task that quickly surpassed the capabilities of their pen-and-paper approach.

Instead, they generated 20,000 simulated, or “fake”, datasets of what present-day genomes might look like for each of five different scenarios, including multiple mixings and dilutions. These were used to train a neural network to distinguish between the different scenarios.

Once trained, Schraiber and Villinea ran their real data – the frequencies of Neanderthal chunks in both Europeans and Asians – to see which model fitted.

“What it spat out was there’s multiple admixtures,” says Schraiber.

Whether this occurred in short bursts or at low levels for an extended period of time is difficult to say, says Schraiber, but dilution in Europe, if it occurred, was a minor contributor.

“It’s not too surprising, but it’s good to have further support [for multiple events],” says evolutionary biologist Alan Cooper from the University of Adelaide, Australia, who was not involved in the study.

The picture remains a complicated one. Early humans mated not only with Neanderthals, but also with Denisovans. And Neanderthals and Denisovans also hooked up.

And while Neanderthal genes flowed into the human lineage, is seems the reverse didn’t occur.

Another big mystery, says Cooper, is why Neanderthals from Western Europe to Eastern Asia are so genetically similar, unlike the Denisovans, which form genetically distinct populations.

More fossils – and more ancient DNA from those fossils – will help to answer such questions.

“I think more so than getting more Neanderthals and Denisovans, getting more modern humans” from across Europe and into Asia, will help to tease out the complexities in human ancestry, says Schraiber.