When researchers extracted and sequenced mitochondrial DNA from the Denisova 11 fragment, they found a Neanderthal-type sequence. The fragment’s mitochondrial genome matched the pattern characteristic of Neanderthals rather than Denisovans or modern humans.
This result, by itself, told researchers something specific: this individual’s mother, or more precisely, the unbroken maternal line stretching back from this individual, was Neanderthal. Mitochondrial DNA identifies the maternal lineage. A Neanderthal mitochondrial signature means a Neanderthal mother—or, more technically, that the individual’s matrilineal ancestry was Neanderthal. In practice, this most likely means the individual’s own mother was Neanderthal, although the mitochondrial signature would be the same if, say, the individual’s maternal grandmother had been Neanderthal and her daughter (the individual’s mother) had been a hybrid. The genetic analysis that followed would clarify which scenario was more likely.
Before the full nuclear genome was sequenced, the mitochondrial result was unusual but not unprecedented. Neanderthal mitochondrial sequences had been found in Denisova Cave before—the cave had previously yielded remains from both Neanderthals and Denisovans. Finding Neanderthal mitochondrial DNA in a fragment from this cave was interesting but not transformative.
The transformation came from the nuclear genome.
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## The Nuclear Genome: A 50-50 Split
Sequencing a full nuclear genome from an ancient bone is a substantially larger undertaking than sequencing mitochondrial DNA. The nuclear genome is roughly 3 billion base pairs, compared to 16,500 in the mitochondrial genome. At the depth of coverage required to make reliable calls from highly damaged ancient DNA, sequencing the nuclear genome requires generating billions of individual sequence reads. Even then, some regions of the genome will be poorly covered or unreadable.