In 2020, scientists studying the genomes  of our closest extinct relatives,   the Neanderthals, found something…weird.

See, we’d already sequenced all of their other  chromosomes, but we’d never been able to get   a good look at the Y-chromosome – one of  the two chromosomes that determines sex… Because the best-preserved remains  just happened to be female.

So the researchers developed a new method  to fish Y chromosome fragments out of the   less-well preserved remains  of three male Neanderthals.

And when they finally managed that,  what they found was totally unexpected.

The Neanderthal Y chromosomes  were much more similar to ours,   Homo sapiens, than they’d anticipated.

In fact, it looked like these Y  chromosomes were from ancient Homo   sapiens, but they were somehow hanging  out in the genomes of male Neanderthals.

So how and why did this Y chromosome end  up replacing the Neanderthal version?

Maybe it’s a bit self-centered that we  can be pretty focused on the DNA that we   got from Neanderthals – but we shouldn’t  forget that gene flow goes both ways.

And the missing Neanderthal Y chromosome points  to a time that we changed their gene pool forever.

Scientists today generally  agree that a group of Homo   sapiens from Africa migrated into  Eurasia around 80,000 years ago.

There, they met and interbred with  the other hominins that already   lived there -- our ancient cousins  the Neanderthals and Denisovans.

And all living people of non-African  descent come from those migrants,   so bits of Neanderthal and Denisovan DNA  can still be found in our gene pool today.

We talked about this in our episode ‘When We  Met Other Human Species’ – but now we want   to flip the script: what happened  when these ancient cousins met us?

From the Neanderthal side, only a small percentage   of their total DNA can be traced  back to interbreeding with us.

Overall, they were much  more similar to Denisovans,   because they were each others’  closest evolutionary relatives.

So the fact that the Neanderthal Y-chromosome was   more like ours than like the  Denisovans’ was a surprise… One that suggests that the  whole thing was completely   replaced in what seems to  be all male Neanderthals!

But when did this Y chromosome  replacement happen–and why?

The interbreeding events that took place around   80,000 years ago and after can’t explain where  Neanderthals got a human-like Y chromosome.

We’d have to look much further back in time.

Scientists have known that there were  multiple human dispersals out of Africa,   some of which didn’t leave modern descendants.

And we still don’t fully understand these ancient   interactions between different hominins  and the implications of those meetings.

But the Y chromosome replacement  points to one of them.

The researchers calculated that the  human-like Y chromosome entered the   Neanderthal gene pool well before  the migration out of Africa around   80,0000 years ago – probably as much as tens  or hundreds of thousands of years before it.

Which means that many of the Neanderthals that   those migrants encountered must have  already had human-like Y chromosomes!

Now, this was a really strange pattern,   unlike what we see in any of the  other Neanderthal chromosomes.

But it wasn't entirely unique.

See, the researchers realized   that a weird pattern had recently been  found in their mitochondrial DNA, too.

Mitochondrial DNA is a small, separate  second genome that is passed down only   from the mother.

And, in Neanderthals, it also  shows a puzzling link with ancient Homo sapiens.

The oldest Neanderthal mitochondrial  genomes we have come from fossils   found in Spain dating to around 430,000 years ago.

And their mitochondrial DNA looks very  Denisovan-like, rather than human-like.

This is what we’d expect, based on  their evolutionary relationship.

But in later Neanderthals, this all changes.

The original Denisovan-like mitochondrial DNA  is missing from all the younger Neanderthals   that we’ve sequenced.

It’s been replaced  with DNA that’s much more human-like.

And in 2017, it was proposed that the best way  to explain this change is a previously unknown   period of very early gene flow between  ancient Homo sapiens and Neanderthals.

Specifically, sometime between 470,000 and  220,000 years ago, a wave of ancient Homo   sapiens from Africa - or a group closely  related to them - migrated into Eurasia.

While this wave eventually died out  without leaving any direct descendants   in modern-day populations, they did leave  a genetic legacy behind in Neanderthals.

At least one female individual from that  group reproduced with a male Neanderthal,   and their hybrid offspring  inherited her mitochondrial DNA.

Those hybrids must have been absorbed  into Neanderthal populations and went   on to reproduce with other Neanderthals.

This allowed female hybrids to  spread their mother’s human-like   mitochondrial DNA through  the Neanderthal gene pool.

Eventually, over tens to hundreds of  thousands of years, this mitochondrial   DNA seems to have completely replaced the original  Denisovan-like mitochondrial DNA in Neanderthals.

So when the researchers later  found human-like Y chromosomes   had also taken over the Neanderthal  gene pool, they realized it must be   another piece of evidence for very  early periods of interbreeding.

The only real difference is that, in this case,   at least one human male had sons with  a female Neanderthal, introducing his   Y chromosome into the Neanderthal gene  pool via those male hybrid offspring.

Now, for us to actually confirm that early  gene flow is behind the Y chromosome situation,   we’d need to find the same evidence  that we have for the mitochondrial DNA.

Namely, we’d need to sequence some  really old male Neanderthals that   predate any gene flow with ancient Homo sapiens.

If and when we manage it, we’d expect  that their Y chromosomes would be like   the original version – the one that looks  more like the Denisovan version than ours.

Right now we only have the replacement Y  chromosome, not the one that was replaced.

Ok, but why did the human mitochondrial DNA and Y   chromosome end up totally pushing out  the ancestral Neanderthal versions?

After all, it’s not like we see this happen  in just a few Neanderthal lineages in a couple   of locations.

As far as we can tell, all  Neanderthals eventually ended up with them.

Well, for such dramatic parallel  replacements to have occurred,   they must have provided some kind of fitness  advantages over the Neanderthal versions.

Now, we don’t know exactly what those advantages  were, but we do have a good idea about why ancient   Homo sapiens DNA might’ve had an edge -  and it all comes down to population size.

See, in small populations, natural selection  is way worse at weeding out harmful mutations,   so they build up at a faster rate than in  bigger populations, all else being equal.

And it’s been argued for a while based  on both fossil and genetic evidence   that Neanderthal population sizes were  pretty small, probably for a long time.

Which means that their Y chromosomes  and mitochondrial genomes probably   had a higher build-up of harmful mutations.

So, as soon as ancient human versions  were introduced, they were immediately   favored by natural selection and rapidly  spread through the Neanderthal gene pool.

As for why we don’t see similar replacements  in the Denisovan gene pool, well, it probably   just came down to distance.

They lived  much further away than the Neanderthals,   and were concentrated in Asia and  Oceania as far as we can tell.

So there would have been less gene flow  between ancient Homo sapiens   and Denisovans during  those early waves of migration – certainly   much less than with Neanderthals, who  lived in the Middle East and Europe.

Together, the Neanderthal Y chromosome  and mitochondrial DNA are two new lines   of evidence that point to a much more  complex and ancient relationship between   us and our closest cousins than  we otherwise would have known.

They hint that ‘the’ out of Africa  migration was only one of several   waves of ancient human dispersals into Eurasia.

And when that successful migration happened around   80,000 years ago, it was only the latest  in a series of encounters between humans   and Neanderthals stretching back tens  to hundreds of thousands of years.

Those Neanderthals had already been  changed forever by the introduction