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New Neanderthal Mitochondrial Genome Suggests Earlier Encounter With Modern Human Lineage

Credit: Photo Museum Ulm
Excavations at the Hohlenstein-Stadel cave in southwestern Germany in 1937 uncovered a 124,000-year-old Neanderthal femur

NEW YORK (GenomeWeb) – Analysis of a newly sequenced Neanderthal mitochondrial genome indicates that Neanderthals and ancestors of modern humans migrating from Africa might have met earlier than previously assumed.

According to prior work that examined nuclear Neanderthal DNA, the Neanderthal and modern human lineages split between 765,000 years and 550,000 years ago. However, mitochondrial DNA evidence had pointed to a more recent divergence some 400,000 years ago.

As Neanderthal mitochondrial DNA is also more similar to that of modern humans than it is to that of their closer Denisovan relatives, some scientists were suspecting that a hominin group closely related to modern humans migrated out of Africa before modern humans did and interbred with Neanderthals to introduce their mitochondrial DNA.

"This scenario reconciles the discrepancy in the nuclear DNA and mitochondrial DNA phylogenies of archaic hominins and the inconsistency of the modern human-Neanderthal population split time estimated from nuclear DNA and mitochondrial DNA," Johannes Krause from the Max Planck Institute for the Science of Human History said in a statement.

To further resolve the relationship between modern humans and Neanderthals, Krause and his colleagues sequenced the mitochondrial genome of a Neanderthal bone found in a cave in southwestern Germany. As they reported this week in Nature Communications, this Neanderthal mitochondrial genome belongs to a lineage that split from other Neanderthal lineages 270,000 years ago. This finding suggests that there was, at one point, greater Neanderthal mitochondrial DNA diversity.

In particular, the researchers extracted DNA from a femur bone that was discovered in a cave. After sequencing and aligning the reads from this sample against a number of references, Krause and his colleagues used the data to construct a phylogenetic tree that also included samples from 54 modern humans, three Denisovans, and 17 other Neanderthals.

The new sample from the Hohlenstein–Stadel cave fell basal to all the other Neanderthal lineages and represented the deepest diverging lineage among known Neanderthal mtDNAs, they reported.

The researchers also uncovered a fairly high contamination level from modern human DNA of between 9.5 percent and 11.5 percent.

Still, Krause and his colleagues used this mitochondrial sequence along with others to estimate mtDNA diversity among Neanderthals. They found that this new sample had an average pairwise nucleotide distance to other Neanderthal mtDNA of 104 positions, which they noted was even higher than that observed among Denisovan pairs and is at the upper range of what's seen among modern humans.

This indicated to them that not only is this sample's mtDNA branch highly divergent from other Neanderthals', but also that Neanderthal mtDNA diversity is greater than had been thought.

Using a molecular Bayesian dating analysis — radiocarbon dating was inconclusive — the researchers placed the new sample's age at 124,000 years. They likewise estimated that its lineage split from other Neanderthals about 270,000 years ago. By contrast, the Altai Neanderthal branch split some 160,000 years ago.

This also establishes a lower bound for when the hominin group that is closely related to modern humans left Africa and interbred with Neanderthals, the researchers added.

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