Green and colleagues announced the Neandertal nuclear genome in tomorrow’s issue of the journal Science. Hitherto only complete mitochondrial DNA (mtDNA) genomes had been recovered. These are only inherited maternally, and the genetic differences between the Neandertal mtDNA and that of modern humans seemed to suggest that Neandertals and humans didn’t mix, that is that they were replaced by “anatomically modern humans” (whatever that phrase means). mtDNA is special as far as genetic stuff goes – only inherited maternally, so only tells about one strain out of a slew of ancestors; doesn’t recombine; as a result, selection acting on a part results on selection of the entire mitochondrial genome; oh and it’s certainly not selectively neutral.

So should we have been wary when it was suggested by mtDNA that neandertals and humans were separate species (recall the issue was even crazier with the Denisova mtDNA specimen…)?

This is a big deal, because for the past several decades researchers have debated the nature of modern human origins. On morphological and shaky mtDNA evidence, several researchers have argued that modern humans emerged from a small African population, which then spread throughout the world between 100-200 thousand years ago and replaced all other ‘archaic’ human populations. Intuitively this doesn’t make sense, and today’s neandertal announcement renders the Out of Africa with Replacement model for human origins absolutely untenable.

So, were Neandertals and (even then-modern) humans the same species? Yes! If Neandertals were a different species, we would expect all humans to be equally genetically divergent from neandertals. But this is not what Green and colleagues found. Rather, the genomes of a French person, a Chinese person, and a Papua New Guinean were actually more similar to the Neandertal genomes than the two African human representatives were to the Neandertals. Such disparate divergences mean we’re dealing with genetic variation within a species, rather than between species.

In fact, the authors estimate that about 1-4% of modern, non-African genomes are derived from Neandertals. Plagnol and Wall (2006) estimated around 5% of human genes come from ‘archaic’ humans, so it is good to see corroborating evidence from two sources. It is interesting, however, that earlier candidates for introgression from archaics, such as the microcephalin haplogroup D, do not appear to have come from Neandertals (maybe another archaic population, then?).

The authors were also able to use these neandertal and modern human genomes to estimate regions of the human genome that have been under recent and accelerated evolution, including:

• SPAG17 is associated with sperm motility – is this evidence for sperm competition and recent sexual selection?
• Regions in which, among modern humans, mutations are associated with social-cognitive diseases like schizophrenia and autism
• RUNX2, again where misexpression in humans is associated with dysgenesis of frontal bone (forehead), shoulder and rib-cage shape morphology

Interesting…

I think the only things I would have loved to have seen in this study are simple logistical issues, things that are probably simply not practical at the moment because of technological constraints. First, I’d love to see a much larger set of modern human reference genomes. The study included only 2 human nuclear genomes from sub-Saharan Africa, 1 from Europe, 1 from China and 1 from Papua New Guinea. Yes, this samples variation from all over the world, but it’s 5 out of nearly 7 billion genomes out there today. At the moment, however, it’s just not that easy to acquire and handle genomic data for many individuals.

Second, I’d like to see nuclear genome comparisons using Upper Paleolithic modern humans – ‘modern human’ contemporaries of Neandertals. The Denisova mtDNA was surprising because, at some 40 ka, its genome was about twice as different from modern humans as the neandertal mtDNA sequences were. Just what kind of genetic diversity are we looking at in ancient (anatomically both ‘archaic’ and ‘modern’) humans?

Green and colleagues should be lauded because of how meticulously they went about this project. They took major pains to circumvent issues of contamination, they maximized the DNA they could obtain in spite of preservation issues, they came up with some clever tests. And their results are really interesting.

Green RE et al. 2010. A draft sequence of the Neandertal genome. Science 328: 710 – 722.

Plagnol V and Wall JD. 2006. Possible Ancestral Structure in Human Populations. PLoS Genetics 2(7): e105