Ancient Sex Scandals: Did We Get It On With Neandertals?

This week, Science published two papers about the genetics of Neandertals from a team of scientists based at the Max Planck Institute of Evolutionary Anthropology. The first (which is the only one anyone seems to really care about) gives a draft version of the entire Neandertal genome - a whopping 4 billion base pairs of DNA. They use this information to look for genomic regions that may have been affected by positive selection in ancestral modern humans that led to their separation from Neandertals, and found some very interesting ones that include genes involved in metabolism and in cognitive and skeletal development.

But, of course, that's not what everyone is saying about this paper. What everyone is talking about is that this study 'proved' ancient people f*cked Neandertals. Not only were there romantic trysts between these different hominid lineages, they led to human-Neandertal hybrids, the evidence of which is written in the genomes of all people from Europe and Asia.

In the words of the media...
There's the blunt and simple: "Modern man had sex with Neanderthals"
Or the creative reversal: "Neanderthals 'had sex' with modern man"
Or, my personal favorite: "Neanderthal Genome Shows Most Humans Are Cavemen"

But what did the paper actually say, and is the authors' conclusion that modern humans and Neanderthals screwed productively the only explanation?

The Neandertal Genome

How did they get the Neandertal genome anyway? Well, they took small powder samples of otherwise fairly useless bones from three female Neandertals, all of which were about 40,000 years old. Through some complicated methods, they turned these bone fragments into libraries of DNA chunks, each less than 200 base pairs long. They then took these fragments and pieced them together, using human and chimp genomes as road maps.

Now, the really tough part isn't getting and aligning sequences from Neandertal bones (though, that's not to say that it's easy). It's making sure you're sequencing the bones and not something else. Over the years, the bones have been handles by people, are coated in bacteria, and in general, are contaminated. When doing genetics work with many, modern-day animals, such contamination isn't as much of an issue - for the most part, primers are specific to one kind of organism or another, and the odds of samples being contaminated by a similar enough organism to matter are low. In my lab, for example, the odds that the samples I make from fish fin clips are contaminated with another fish's DNA are pretty low, so there's little worry that my primers will amplify something other than the gene I want.

But these guys are trying to amplify DNA from a creature that is very, very much like us. Furthermore, they don't know what to expect in terms of sequence, and have to use primers that are a little more universal to all primate species. This means that if even one skin cell from one of the scientists falls into a PCR tube, they'll be amplifying the wrong DNA to get their genome sequence. Such contamination has been a big issue in the past studies on Neandertal genetics. In this study, the authors went to every extreme to prevent contamination. Still, they estimate that human contamination in their samples may be as high as 0.5% for the mitochondrial genome and 1.53% for the nuclear genome. I'll explain why that matters in a bit.

The Good Stuff: What They Found

So what did they find? Well, for one, the divergence between human and Neandertal genomes was just a hair under 12.7%. Though you may have heard that you're 98% chimp, the actual sequence divergence between humans and chimps is actually closer to 30%, and scientists have estimated that this represents somewhere between 5.6 to 8.3 million years of separated evolution. Using that as a reference, Green and colleagues estimated that humans and Neandertals diverged about 825,000 years ago. But that's not the whole story, as any two people will have a certain amount of divergence between their genomes. The team also looked at the divergence between native people from Africa, Asia and Europe, and found that the overall sequence divergence between any two people was 8.2% to 10.3%. The Neandertal was significantly more divergent from modern humans than lineages of modern humans are from each other, but the new information changed the time line a little. In the end, they estimate that modern humans and Neandertals became distinct between 270,000 and 440,000 years ago

What the scientists really wanted to know, though, was what was different. Were there clues to how human intelligence, or any other traits, evolved, based on the information contained in our closest relatives? A large part of the paper sought to find evidence of positive selection on the human lineage after the split from Neandertals.

They did this two ways. First, they looked for genes that were the same in Neandertals and chimpanzees, orangutans, and rhesus macaques, but were very different in us. There weren't as many differences as you might think. Only 78 of our 20,000 or so protein genes have changed their amino acid sequence since the split from Neanderthls. They also found 268 changes in sequences that don't code for proteins, but instead function other ways, like as promoters, silencers, or microRNAs.

They also looked for stretches of genetic material that are symptomatic of natural selection. How does a set of genes "look" like it's undergone selection? Well, when a single allele (variation of a gene) is strongly favored due to selection, its proportion in the population rises. Sometimes, it becomes so common that the rest of the alleles disappear, and this is what is called a "selective sweep." Scientists can find these sweeps by looking at Single Nucleotide Polymorphisms (SNPs), or areas that differ by a single base pair. Most of the areas that look this way between chimps and people are similar between people and Neandertals, because they occurred after hominids split from primates but before the human-Neandertal break. But, some have occurred since. In all, they found 212 regions that showed evidence of this kind of selection.

Somewhere, in those 350-550 odd changes, is likely what makes us so different from anything else that has every lived - where, though is still a mystery.

But wait - what about the sex?

Yeah, yeah, I'm getting to it. Geez! Y'all have a one-track mind.

After plowing through most of the paper, one arrives at a section titled "Neandertals are closer to non-Africans than to Africans." In it, the scientists lay out their argument for inter-species sex. What they did to determine this, in their own words was:

"To test whether Neandertals are more closely related to some present-day humans than to others, we identified SNPs by comparing one randomly chosen sequence from each of two present-day humans and asking if the Neandertals match the alleles of the two individuals equally often. If gene flow between Neandertals and modern humans ceased before differentiation between present-day human populations began, this is expected to be the case no matter which present-day humans are compared."

So they looked at how frequently the Neandertal genome matched each of the people from different locations to see if one lineage of modern humans was more similar to the Neandertals than another.

They found that when they compared a European and an Asian to the Neandertals, there was no significant difference. But when they compared an African and any non-African lineage, the Africans were less similar to the Neandertals than other people. They estimate that 1-4% of non-Africans genome is Neandertal genes.

Now, the obvious first question is whether or not contamination explains this. After all, they said the Neandertal nuclear sequences could have as high as 1.53% human contamination - which seeing as the scientists themselves are of Eurasian decent, would certainly skew the Neandertal's genome that direction. But they do give good explanations as to how it's not likely that this effect is due to contamination (which involve some complex math and stats that I just can't see an easy way to break down).

The media stopped reading the paper right about there. Indeed, the authors strongly believe that their data suggest that people and Neandertals interbred. But there are other explanations, even given by the authors, that would cause the patterns they saw.

For example, it's possible that Neandertal's didn't split from all people, but a subset that was on its way to becoming Eurasians. This is known as the "substructure within Africa" hypothesis, where different groups of modern humans actually began splitting before leaving the continent in search of the rest of the world. Carl Zimmer explains this idea rather nicely:

"Cast your mind back 500,000 years, before the populations of humans and Neanderthals had diverged. Imagine that those ancestral Africans were not trading genes freely. Instead imagine that some kind of barrier emerged to keep some gene variants in one part of Africa and other variants in another part.

Now imagine that the ancestors of Neanderthals leave Africa, and then much later the ancestors of Europeans and Asians leave Africa. It's possible that both sets of immigrants came from the same part of Africa. They might have both taken some gene variants with them did not exist in other parts of Africa. Today, some living Africans still lack those variants. This scenario could lead to Europeans and Asians with Neanderthal-like pieces of DNA without a single hybrid baby ever being born."

The substructure in Africa hypothesis is somewhat supported by other genetic and paleontological analyses. Indeed, the authors note that they "cannot currently rule out a scenario in which the ancestral population of present-day non-Africans was more closely related to Neandertals than the ancestral population of present-day Africans due to ancient substructure within Africa"

There's another possible explanation, too, that the authors didn't bring up: selection.

Let's jump back those 500,000 years and take a look at our pre-split hominid population. Let's say, just for argument's sake, that a given region had 10 variations in that group of individuals - we'll label them A, B, C, D, E, F, G, H, I and J. Now, a group of them breaks northward. Due to founder effects, this small group only has A, B, C, D and E to start with. As the rugged north takes its toll, certain variations prove more useful - A and B, for example. Soon enough, genetic drift and selection leaves this population with only A, B and D.

Meanwhile, the original population in Africa has been evolving. They have A. B. C. D. E. F. G. H, I, J and how K, L, M, N and O. A small group from that population breaks off, too, and follows the path taken by the first subgroup hundreds of thousands of years earlier. Again, due to founder effects, this new little group has only a small amount of the variation that is in Africa - they take with them A, B, C, E, F, G, H, I, M, N, and O. As they face the frigid winds and weakened sun, they are whittled down to only those that give them the best advantage in the north - A, B, C, E, F, and O.

Meanwhile, the African population is evolving, too. They find that some of their variations give them a better chance in the African sun, like H through O. Over time, A, B and C just disappear.

So now you have one population with A, B and E, one with A, B, C, E, F and O, and one with E, F, G, H, I, J, K, L, M, N and O. Although the two groups that stayed in Africa longer are more closely related, the group that left first will be more similar to the second split off group because selection favored the same variations in both that were present before the first split occurred. So you see, it's possible that selection could explain some of the similarity between Eurasians and Neandertals, without a single person getting hanky-panky with another hominid.

That's not to say that the hybridization hypothesis is without merit. Indeed, the authors did a damned good job presenting their case, and their reasoning is sound. The point I'm making is that sex isn't the only option. And if hybridization did occur to the extent they predict, we're likely to find more hints at its existence. Analyzing the DNA of some of the suspected hybrid fossils, for example, might settle it once and for all. Or we may never know if the gene variants that are similar between Eurasians and Neandertals are due to sex, selection, or substructure. Time may have simply destroyed too much of the evidence for us to be sure.

What is certain is that sex sells, which is why the only thing the media is talking about when it comes to this paper is that ancient people may have shagged their evolutionary siblings. It's just so damned frustrating because the sexual exploits of early humans is only the tiniest piece of this huge discovery. Oh, the things we may learn from this genome about our own evolution, and our closest relatives! Whether we had sex with Neandertals or not, the work this team has done will change forever our understanding of hominid evolutionary history. The impact this genome will have on the science of human evolution is huge. The breakthrough science, the future implications of this work - that's what the media should be talking about - not ancient sex scandals.



Green, R., Krause, et al. (2010). A Draft Sequence of the Neandertal Genome Science, 328 (5979), 710-722 DOI: 10.1126/science.1188021