The team at the Max Planck Institute for Evolutionary Anthropology, led by Viviane Slon as first author and Svante Pääbo as senior author, performed this sequencing on the Denisova 11 fragment. The genome was sequenced at approximately 2.6-fold average coverage—meaning that, on average, each position in the genome was read approximately 2.6 times. This is lower coverage than is typically used for high-confidence genomic conclusions, but the Denisova Cave material had been sequenced using multiple independent libraries, and the researchers used statistical methods to handle the uncertainty created by lower coverage.
When they analyzed the nuclear genome, they found a pattern that was immediately and dramatically different from anything that had been found before.
The nuclear genome is inherited from both parents—one copy of each chromosome comes from the mother, one from the father. When researchers compare an ancient nuclear genome to reference sequences from Neanderthals and Denisovans, they can assess what fraction of the genome looks Neanderthal-like and what fraction looks Denisovan-like. For a typical individual from either group, the answer is straightforward: a Neanderthal’s genome looks almost entirely Neanderthal, with perhaps a small percentage reflecting earlier admixture with other groups; a Denisovan’s genome looks almost entirely Denisovan.
The Denisova 11 nuclear genome looked approximately half Neanderthal and half Denisovan.
This was the finding that made Pääbo, by his own account, initially disbelieve the result. “I initially thought that they must have screwed up in the lab,” he said after the study’s publication. The proportion was so even, the mixture so nearly balanced, that it was hard to credit as a real biological signal rather than a technical error. But replication and analysis confirmed the result. The genome was not contaminated or mixed by accident. The DNA itself carried this signature because the individual who grew this bone carried one set of chromosomes from a Neanderthal-ancestry parent and another set from a Denisovan-ancestry parent.