Neanderthal Mitochondrial and Nuclear DNA
Ancient DNA has been extracted from Egyptian mummies and from extinct animals such as quaggas, mammoths, saber-tooth cats, giant ground sloths, moas, and marsupial wolves. The first analysis of any Neanderthal DNA was mitochondrial DNA (mtDNA), published in 1997. The sample was taken from the first Neanderthal fossil discovered, found in Feldhofer Cave in the Neander Valley in Germany. A small sample of bone was ground up to extract mtDNA, which was then replicated and analyzed.
Researchers compared the Neanderthal mtDNA to modern human and chimpanzee sequences and found that the Neanderthal mtDNA sequences were substantially different from both (Krings et al. 1997, 1999). Most human sequences differ from each other by an average of 8.0 substitutions, while the human and chimpanzee sequences differ by about 55.0 substitutions. The Neanderthal and modern human sequences differed by approximately 27.2 substitutions. Using this mtDNA information, the last common ancestor of Neanderthals and modern humans dates to approximately 550,000 to 690,000 years ago, which is about four times older than the modern human mtDNA pool. Since this study was completed, many more samples of Neanderthal mtDNA have been replicated and studied.
While there is no current evidence that Neanderthals contributed to the modern mtDNA gene pool, it is possible that the evidence of such admixture is obscured for a variety of reasons (Wang et al 2013). Primary among these reasons is sample size: There are to date only a dozen or so mtDNA sequences that have been sampled. Because the current sample of Neanderthal mtDNA is so small, it is possible that researchers simply have not yet found the mtDNA in Neanderthals that corresponds to that of modern humans.
Sequencing the Complete Neanderthal Mitochondrial Genome
After successfully sequencing large amounts of DNA, a team led by Svante Pääbo from the Max Planck Institute reported the first complete mitochondrial DNA (mtDNA) sequence for a Neanderthal (Green et al. 2008). The sample was taken from a 38,000 year old Neanderthal from Vindija Cave, Croatia. The complete mtDNA sequence allowed researchers to compare this Neanderthal mtDNA to modern human mtDNA to see if any modern humans carried the mtDNA from a related group to the Neanderthal group.
Later, Svante Pääbo’s lab sequenced the entire mitochondrial genome of five more Neanderthals (Briggs et al. 2009). Sequences came from two individuals from the Neander Valley in Germany and one each from Mezmaiskaya Cave in Russia, El Sidrón Cave in Spain, and Vindija Cave in Croatia. Though the Neanderthal samples came from a wide geographic area, the Neanderthal mtDNA sequences were not particularly genetically diverse. The most divergent Neanderthal sequence came from the Mezmaiskaya Cave Neanderthal from Russia, which the oldest and eastern-most specimen. Further analysis and sampling or more individuals has led researchers to believe that this diversity was more closely related to age than it was to population-wide variance (Briggs et al. 2009).
On average, Neanderthal mtDNA genomes differ from each other by 20.4 bases and are only 1/3 as diverse as modern humans (Briggs et al. 2009). The low diversity might signal a small population size, possibly due to the incursions of modern humans into their range. The image at right shows the extent of the geographic area inhabited by Neanderthals, based on fossil evidence.
Sequencing the Neanderthal Nuclear Genome
There have been many efforts to sequence Neanderthal nuclear genes, with an eventual goal to sequence as much of the Neanderthal genome as possible. In 2014, the complete genome of a Neanderthal from the Altai Mountains in Siberia was published (Prufer et al 2014). This female individual’s genome showed that her parents were likely half siblings and that her genetic line showed evidence of high rates of incestuous pairings. It is unclear whether this is due to her living in a small and isolated population or if other factors may have influenced the lineage’s inbreeding. Their analysis also showed that this individual was closely related to both modern humans and the Denisovans. By their analysis, there was only a very small margin by which Neanderthal and Denisovan DNA differed exclusively from modern humans.
Neanderthals are genetically distinct from modern humans, but are more closely related to us than chimpanzees are
The Neanderthal and modern human lineages diverged about 550,000 years ago
So far, we have no evidence of Neanderthal mtDNA lineages in modern humans
Neanderthals were not as genetically diverse as modern humans were at the same period, indicating that Neanderthals had a smaller population size
Neanderthal nuclear DNA shows further evidence of small population sizes, including genetic evidence of incest
As technology improves, researchers are able to detect and analyze older and more fragmentary samples of DNA