LEIPZIG, GERMANY—Scientists have extracted and analyzed DNA from the 50,000-year-old toe bone of a Neanderthal woman found in Siberia's Denisova Cave in 2010 and put together a high-quality draft of the genome of modern human's closest extinct relative. The sequence allows for comparison between modern humans and other hominins, like Denisovans, another extinct hominin. For example, about two percent of the DNA of modern humans living in outside of Africa is from Neanderthals. The research also showed that Neanderthals and Denisovans interbred but not to the extent that there was a lot of genetic crossover—the Denisovan genome gets less than one percent of its genes from Neanderthals. Further, an unidentified human ancestor may have contributed up to six percent of the genes in the Denisovan genome. “This ancient population of hominins lived prior to the separation of Neanderthals, Denisovans and modern humans,” says Kay Prüfer, a researcher at the Max Planck Institute for Evolutionary Anthropology, Leipzig. “It is possible that this unknown hominin was what is known from the fossil record as Homo erectus.”
Here are the major insights of the present study:
The new genome appears to represent an individual that has fewer new derived mutations than the Denisovan high-coverage genome. The research suggests this as a means of "molecular dating" of the specimens, proposing that the Denisovans lived in Denisova cave after this Neandertal population.
The Denisovan high-coverage genome includes portions that reflect ancestry from Neandertals.
The new genome groups with previously known Neandertals in a genome-wide cluster analysis, but represents a more divergent population of Neandertals than those yet described. Under a model where genetic differences reflect a branching population history, the "Altai Neandertal" population seems to have diverged from other Neandertals sometime between 77,000 and 114,000 years ago.
The high-coverage Neandertal genome shares many derived mutations with sub-Saharan Africans, while the high-coverage Denisova genome shares fewer. If these archaic populations were equally related to Africans, they would have the same number of shared derived mutations with Africans. Prüfer and colleagues infer that the Denisovan genome had ancestors who belonged to a yet more ancient hominin population. They suggest this population represents around 4 percent of the ancestry of Denisovans, and that it diverged from the common ancestors of Neandertals and sub-Saharan Africans sometime around a million years ago. The confidence intervals on both estimates are large.
The new genome has many extended runs of homozygosity, consistent with inbreeding. The study concludes that the parents of this individual were likely 1/4 degree relatives -- such as uncle/niece or half-sibling mating.
A comparison of the archaic human genomes with the 1000 Genomes Project samples shows only 96 amino-acid-coding changes shared by nearly all of the 1094 recent humans but absent from Denisovan and Neandertal genomes. A larger number (over 3000) of mutations that "possibly affect gene regulation" are also near fixed in recent humans. These are potentially interesting because they may be related to recent behavioral or anatomical evolution of modern humans.
The paper reports on new sequencing of the Mezmaiskaya Neandertal to 0.5x coverage. This genome is substantially closer to recent humans than are the other Neandertal genomes. Presumably the population of Neandertals that accounts for present-day Neandertal genes in living people was closer to the Mezmaiskaya Neandertal than others.
The high-coverage Neandertal and Denisova sequences allow a new estimate of the amount of Neandertal and Denisovan ancestry in human populations. Neandertal ancestry of living non-Africans is now estimated between 1.5 and 2.1 percent. This is lower than previous estimates, a discrepancy that the paper does not explain.
The paper finds significant evidence for Denisovan ancestry of mainland Asian and Native American populations. The Denisovan fraction in these populations is small, only around two tenths of a percent on average, but the ancestry is spread throughout these populations into the New World.
The Denisovan ancestry of living populations of New Guinea represents a substantially different genetic background than the Denisova high-coverage genome. The divergence between the Siberian Denisovan high-coverage genome and the Denisovan intermixture with humans is greater than the divergence between any living groups of humans with each other.
We can now see that the original description of the Denisovan genome in 2010 and follow-up analyses in 2011 were based on a number of inaccurate assumptions. The current high-coverage data have added a lot of precision to some analyses, but several of the changes in this new research have actually come from the adoption of new assumptions and more refined models.
Some of the conclusions in this paper will not last long as more ancient genomes are sequenced. We have recently seen with the publication of the Sima de los Huesos mtDNA that many assumptions about the Denisova population are questionable ("The Denisova-Sima de los Huesos connection").
Why should we assume that the Denisovan ancestry includes only a single "mystery population"? The Sima de los Huesos result shows that several populations may have been in a position to mix with the ancestors of Denisovans.
Why should we assume that the Denisovans were a single population? The genetic differences among "Denisovan" groups by our current definition were greater than those between any two human groups today.
This current paper is noncommittal about the rate of mutations that should be applied to the ancient genomes, which leads to an uncertainty of more than a factor of two in the date estimates presented. This is unfortunate because the uncertainty prevents the DNA from shedding light on the relationships of pre-Neandertal, Neandertal and modern human fossil remains. But the uncertainty is real, as the relevant mutation rates remain a matter of debate ("A longer timescale for human evolution", "What is the human mutation rate?").
At any rate, the new genome has tremendous value for the further study of how we evolved. As I continue to study the supplements of the paper, I will be updating on several areas of interest.