Oldest Sequenced Genome From 45,000-Year-Old DNA

In a technological tour de force, a group of scientists have managed to read most of the DNA from the thigh bone of a 45,000-year-old man. This is by far the most ancient human genome sequenced to date.

We can see Neanderthal DNA much more clearly in this ancient man’s DNA than we can in modern human DNA because he lived at a time much closer to when humans and Neanderthals did a lot of meaningful mating. It is getting very hard to refute the idea that people outside of Africa owe a bit of who they are to Neanderthals.

These researchers could also use this ancient DNA to more precisely estimate that most of the Neanderthal DNA we see in modern people’s DNA entered into the human gene pool around 50,000-60,000 years ago. This is a much narrower window then the previous estimate of 37,000-86,000 years ago.

Finally, the researchers used this DNA to get a better estimate of how much human DNA has changed from generation to generation over the years. In agreement with some recent data, they found that this mutation rate was slower than previously thought. If this lower number is closer to the real mutation rate over the last few million years, then chimpanzees and humans probably shared a common ancestor 10-11 million years ago instead of the 6-7 million years ago scientists previously thought.

Longer Stretches, More Closely Related

Over the last few years, better technology has allowed scientists to sequence many ancient DNAs including that of our close relatives, the Neanderthals. By comparing this Neanderthal DNA to that of many modern humans, scientists have been able to see bits of Neanderthal DNA lurking in many people’s DNA but not in any of the DNA of Africans.  From this scientists concluded that humans and Neanderthals probably had many children together sometime after humans left Africa to colonize the rest of the world.

A big problem in figuring out when this happened is that there are only the tiniest wisps of Neanderthal DNA in modern human DNA. It has simply been too long since Neanderthals and humans had any significant amounts of interbreeding to get a good estimate from modern DNA.

This is why the 45,000 year old DNA lets scientists make a more precise estimate of when these pairings happened. The ancient man was alive at a time that was much closer to when humans and Neanderthals successfully mated.

Now this doesn’t mean he had more Neanderthal DNA in his DNA than modern humans do because he didn’t. Around 2.3% of his DNA was Neanderthal compared to the 1.7-2.1% in modern people’s DNA. This is well within the margin of error.

No, instead of more Neanderthal DNA, he had longer stretches of it. And this is just what we would have expected given how DNA is passed on.

Mixing and Matching DNA

DNA is stored in cells in long pieces called chromosomes. Most people (and Neanderthals) have two copies of each of their chromosomes, one from mom and one from dad.

When someone has a baby, only one of each pair is passed down to the child. But the child almost never gets an exact copy of either one that the parent had.

Before chromosomes are packaged into a sperm or egg, each chromosome in a pair swaps DNA with its partner in a process called recombination. The resulting mixed chromosome is then passed down to a child. Here is what this might look like for one chromosome:

As you can see the new chromosome has a bit from the blue chromosome and a bit from the red one. Keep in mind that the new chromosome didn’t have to turn out exactly like this. It could have been that there was no mixing or that different parts got mixed. The key point here is that parents and children will share large chunks of their DNA.

Of course we get a chromosome from each parent so here is what someone’s pair of chromosomes might look like from his or her parents:

This person got a mix of red and blue from one parent and a mix of green and yellow from the second. Here is an example of a chromosome he or she might pass down:

Now you can see that the shared bits of DNA are a bit smaller. There is less red and a whole lot less blue than there was in the original.

As we get further and further away in time from the original blue and red chromosomes, the bits get smaller and smaller. We can use the size of the shared DNA to make reasonable guesses about how far back two people are related.

If scientists had DNA from the original person with the red and blue chromosomes, they could tell that this person was more closely related to his or her child and more distantly related to the grandchild. This is a grossly oversimplified version of how genetic testing companies like 23andMe or AncestryDNA find your long lost relatives.

After all these years, the pieces of Neanderthal DNA in modern humans are tiny. So small, in fact, that it is hard to get a precise estimate as to when humans and Neanderthals first had sex in any meaningful way.

The 45,000 year old DNA is a different matter though. The Neanderthal ancestors were much closer to his time so that scientists could tell that Neanderthals and his ancestors had bred around 7,000-13,000 years before this man was alive. That is where they got the 50,000-60,000 year range.

The authors were careful to point out that this does not mean that there were no more Neanderthal-human pairings after this. There may still have been the occasional dalliance but these would not have been the major contributors to the Neanderthal DNA we see in people’s DNA today.

Finding out when humans and Neanderthals bred is not the only finding reported in this study. The researchers also provided additional evidence that humans and chimpanzees probably shared a common ancestor 10-11 million years ago instead of the 6-7 million years scientists previously thought.

Recalculating Human-Chimp Split

Each time we pass on our DNA to the next generation, our cells make a few mistakes (click here for why that is). These new mutations are thought to happen at a fairly steady rate. Scientists are able to compare the DNA of different species and to estimate when they shared a common ancestor based on this mutation rate.

Based on what they thought the mutation rate was, scientists hypothesized that humans and chimpanzees shared a common ancestor around 6 or 7 million years ago. Turns out that the actual number may be closer to 10 or 11 million years ago.

We get to this new estimate because with the advent of cheap and easy DNA sequencing, scientists can directly calculate the mutation rate in people. They have done this by comparing children’s DNA to their parent’s DNA and looking for differences. And in this study, the researchers calculated the mutation rate by comparing modern DNAs to that of the 45,000 year old man. The two results roughly agree.

The authors point out that we need to keep in mind that this estimate relies on the mutation rate being constant over the last 10 or 11 million years. We do not yet have direct proof that this is the case. At the very least we can conclude that the mutation rate probably stayed fairly constant over the last 45,000 years or so.