Neanderthals were first recognized as a distinct group of hominids from fossil remains discovered 150 years ago at Feldhofer in Neander Valley, outside Düsseldorf, Germany. Subsequent Neanderthal finds in Europe and western Asia showed that fossils with Neanderthal traits appear in the fossil record of Europe and western Asia about 400,000 years ago and vanish about 30,000 years ago. Over this period they evolved morphological traits that made them progressively more distinct from the ancestors of modern humans that were evolving in Africa1,2. For example, the crania of late Neanderthals have protruding mid-faces, brain cases that bulge outward at the sides, and features of the base of the skull, jaw and inner ears that set them apart from modern humans3.

The nature of the interaction between Neanderthals and modern humans, who expanded out of Africa around 40,000–50,000 years ago and eventually replaced Neanderthals as well as other archaic hominids across the Old World is still a matter of some debate. Although there is no evidence of contemporaneous cohabitation at any single site, there is evidence of geographical and temporal overlap in their ranges before the disappearance of Neanderthals. Additionally, late in their history, some Neanderthal groups adopted cultural traits such as body decorations, potentially through cultural interactions with incoming modern humans4.

In 1997, a segment of the hypervariable control region of the maternally inherited mitochondrial DNA (mtDNA) of the Neanderthal type specimen found at Feldhofer was sequenced. Phylogenetic analysis showed that it falls outside the variation of contemporary humans and shares a common ancestor with mtDNAs of present-day humans approximately half a million years ago5,6. Subsequently, mtDNA sequences have been retrieved from eleven additional Neanderthal specimens: Feldhofer 2 in Germany7, Mezmaiskaya in Russia8, Vindija 75, 77 and 80 in Croatia9,10, Engis 2 in Belgium, La Chapelle-aux-Saints and Rochers de Villeneuve in France10, Scladina in Belgium11, Monte Lessini in Italy12, and El Sidron 441 in Spain13. Although some of these sequences are extremely short, they are all more closely related to one another than to modern human mtDNAs9,11.

This fact, in conjunction with the absence of any related mtDNA sequences in currently living humans or in a small number of early modern human fossils5,10 strongly suggests that Neanderthals contributed no mtDNA to present-day humans. On the basis of various population models, it has been estimated that a maximal overall genetic contribution of Neanderthals to the contemporary human gene pool is between 25% and 0.1% (refs 10, 14). Because the latter conclusions are based on mtDNA, a single maternally inherited locus, they are limited in their ability to detect a Neanderthal contribution to the current human gene pool both by the vagaries of genetic drift and by the possibility of a sex bias in reproduction. However, both morphological evidence4,15 and the variation in the modern human gene pool16 support the conclusion that if any genetic contribution of Neanderthals to modern human occurred, it was of limited magnitude.

Neanderthals are the hominid group most closely related to currently living humans, so a Neanderthal nuclear genome sequence would be an invaluable resource for annotating the human genome. Roughly 35 million nucleotide differences exist between the genomes of humans and chimpanzees, our closest living relatives17. Soon, genome sequences from other primates such as the orang-utan and the macaque will allow such differences to be assigned to the human and chimpanzee lineages. However, temporal resolution of the genetic changes along the human lineage, where remarkable morphological, behavioural and cognitive changes occurred, are limited without a more closely related genome sequence for comparison. In particular, comparison to the Neanderthal would enable the identification of genetic changes that occurred during the last few hundred thousand years, when fully anatomically and behaviourally modern humans appeared.