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Ancient Mitochondrial Genome Points to Previously Unknown Hominin Group

By Andrea Anderson

NEW YORK (GenomeWeb News) – An international research team reported online in Nature today that they have sequenced an ancient mitochondrial genome representing a previously unrecognized type of hominin, the evolutionary group containing modern human and Neanderthal lineages.

The researchers used the Illumina platform to sequence mitochondrial DNA from a 30,000 to 50,000 year old finger bone found in Siberia's Denisova Cave. By comparing the sequence to mitochondrial genomes from Neanderthals and modern humans, the team found evidence suggesting the new mitochondrial genome represents a hominin mitochondrial group that branched off earlier than Neanderthal or modern human mitochondrial lineages.

Those involved say more research is needed to understand whether the Denisova specimen — dubbed "X woman" to reflect the maternal nature of mitochondrial inheritance — actually belonged to this new hominin group.

Nevertheless, the findings point to a more complex and interesting hominin history than appreciated thus far, senior author Svante Pääbo, director of the genetics department at the Max Planck Institute for Evolutionary Anthropology, told reporters during a telephone press briefing yesterday.

Lead author Johannes Krause, also at the Max Planck Institute for Evolutionary Anthropology, told reporters that he first got wind of the new mitochondrial sequence while screening DNA from archaeological specimens.

When he examined DNA from a pinky finger bone unearthed in the Altai Mountains of southern Siberia in 2008, Krause saw something that "really looked like something that I'd never seen before."

Based on this screen, the researchers decided to do more detailed sequence analysis of the Denisova specimen, which has been dated at between about 30,000 and 48,000 years old.

The bone appears to have come from a five- to seven-year-old individual and was found in the same region as remains from modern humans, Neanderthals, woolly mammoths, and woolly rhinos, Pääbo noted.

After authenticating the DNA, the researchers used their primer extension capture method — described by our sister publication In Sequence last summer — to enrich for mitochondrial DNA.

The team then sequenced mitochondrial genome fragments using the Illumina Genome Analyzer II platform, generating enough sequence to cover each base in the mitochondrial genome a mean of 156 times. They also verified the sequence through independent shotgun sequencing experiments.

When they compared the mitochondrial genome with mitochondrial genomes from 54 present day humans, one ancient modern human, six Neanderthals, a bonobo, and a chimpanzee, the researchers found that the Denisova specimen sequence was distinct from that found in either modern humans or Neanderthals.

The mitochondrial genome differed from present day human mitochondrial sequences at an average of 385 positions. In contrast, the team noted, Neanderthal and human mitochondrial sequences vary at about half as many sites — 202 bases, on average.

That suggests that the common mitochondrial ancestor between this new mitochondrial group and modern humans is about twice as old as the mitochondrial ancestor shared by modern human and Neanderthal lineages.

And phylogenetic results so far indicate that the X woman's mitochondrial genome branched off earlier than either the Neanderthal or human lineages, sharing a mitochondrial ancestor with the other two hominin groups roughly a million years ago.

Past studies have found evidence for at least three hominin migrations out of Africa: Homo erectus is thought to have migrated from the continent roughly 1.9 million years ago, while Neanderthal and modern human ancestors are thought to have migrated from Africa much more recently — 300,000 to 500,000 years ago and around 50,000 years ago, respectively.

But Pääbo says the new findings suggest hominin migrations might not have been as discrete or limited as once believed. Instead, he noted, it's possible that there was more continuous gene flow out of Africa than is reflected in past research.

"There might be more such surprises in store for us," Pääbo predicted.

Indeed, the team noted, the new mitochondrial data combined with fossil findings representing apparently new hominin forms (such as the 17,000-year-old "hobbit," H. floresiensis, remains found in Flores, Indonesia) suggest several hominin groups might have overlapped in some parts of the world.

"[T]he presence of Homo floresiensis in Indonesia about 17,000 years ago and of the Denisova mtDNA lineage in southern Siberia about 40,000 years ago suggest that multiple Late Pleistocene hominin lineages co-existed for long periods of time in Eurasia," the researchers wrote.

So far, attempts to isolate and characterize H. floresiensis DNA have been unsuccessful, Pääbo said.

But despite the unique mitochondrial sequence detected in the Denisova finger sample, the team stopped short of saying the individual sampled actually represents a new species.

Pääbo emphasized that the mitochondrial sequence is "still just one part of our genome" and said nuclear genome sequencing is needed to determine whether the individual belongs to a new hominin group or whether the individual carries the mitochondrial genome due to prior cross-breeding events.

The team is currently sequencing the nuclear genome from the X woman specimen, which Pääbo said is expected to yield at least enough sequence data to begin addressing questions about the individual's relationship to modern humans and Neanderthals.

In addition, Krause noted that sequencing more mitochondrial genomes from Neanderthals, modern humans, and other hominins should provide a clearer picture of population patterns and sizes within hominin groups.