Israeli Researchers Reconstruct Prehistoric Humans called ‘Denisovans’

Then the man said, “This one at last is bone of my bones and flesh of my flesh. This one shall be called Woman, for from man was she taken.” Genesis 2:23 (The Israel Bible™)

Using high-grade DNA taken from the pinky bone of “Denise,” a prehistoric Denisovan girl who lived 70,000 years ago and died in a Siberian cave at the age of 13, Hebrew University of Jerusalem-Israel (HUJI) scientists have for the first time accurately reconstructed the anatomy of these early humans, whose civilization was sandwiched in time between Neanderthals and modern hominins.

The discovery and later the HUJI analysis of her pinky bone has opened a new chapter in the understanding of human evolution.

The team led by HUJI researchers Prof. Liran Carmel of the Alexander Silberman Institute of Life Science  and Dr. David Gokhman (currently a postdoctoral fellow at Stanford University) has produced reconstructions of these long-lost relatives based on patterns of methylation (chemical changes) in their ancient DNA. Their monumental article appears in the latest issue of the scientific journal Cell, with an accurate image of Denise based on a sweet-faced plaster head on the cover that was created by artist Ma’ayan Harel over a period of weeks.

Prof. Liran Carmel and plaster head of Denise (credit)

If you could travel back in time to 100,000 years ago, you’d find yourself living among several different groups of humans, including Modern Humans (those anatomically similar to us), Neanderthals and Denisovans.  We know quite a lot about Neanderthals, thanks to numerous bones and other remains found across Europe and Asia.  But exactly what our Denisovan relatives might have looked like had been anyone’s guess for a simple reason – the entire collection of Denisovan remains includes three teeth, a girl’s tiny pinky bone and a lower jaw.

In 2010, scientists announced the discovery of an undated finger bone fragment of a juvenile female found in the Denisova Cave in the Altai Mountains in Siberia – a cave named for a hermit, Dyonisty (Denis) who lived there in the 18th century, that had also been inhabited eons before by Neanderthals and modern humans. Some Denisovans lived there between 287,000 and 55,000 years ago.

Various bones from various wild animals had previously been found there. The mitochondrial DNA of Denise’s finger bone showed it to be genetically distinct from Neanderthals and modern humans.

“We provide the first reconstruction of the skeletal anatomy of Denisovans,” said lead author Carmel at a Thursday press conference on HUJI’s Givat Ram campus in Jerusalem. “In many ways, Denisovans resembled Neanderthals but in some traits they resembled us and in others they were unique.”

Profs. Eran Meshorer from the Hebrew University, Yoel Rak from Tel Aviv University, and Tomas Marques-Bonet from Barcelona’s Institute of Evolutionary Biology (UPF-CSIC) contributed to this research.

HU Research and Development vice president Prof. Re’em Sari told the journalists: “This is a celebration for science. Our researchers’ findings show the great ability of our sophisticated HU labs.”

Prof. Erella Hovers, a HU paleo-anthropologist who was not part of the team, added that the Siberian cave is 700 meters high and 270 square meters in size, with a main, east and south chambers. Most of the excavation has been done by Russians; Israelis did not take part in the disk but conducted their pathfinding research based on data provided via computer from the archeologists.

DNA methylation is a process by which methyl groups (alkyls derived from methane) are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the DNA sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription.

In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprintingX-chromosome inactivation, repression of transposable elementsaging, and carcinogenesis.

Denisovan remains, first discovered in 2008, have fascinated human evolution researchers ever since. They lived in Siberia and Eastern Asia and went suffered extinction about 50,000 years ago, but the reasons for this are not known. Still, up to 6% of Melanesians and Aboriginal Australians alive today contain Denisovan DNA. In addition, Denisovan DNA likely contributed to modern Tibetans’ ability to live in high altitudes and to ability of Inuits in the Arctic and Greenland to withstand freezing temperatures.

Although there so far are no practical applications today, Carmel said that eventually, forensic experts in the police could use DNA methylation to better identify criminals from DNA left at the scene.

Overall, Carmel and his team identified 56 different anatomical features – 34 of them in the skull – in which Denisovans differ from modern humans and/or Neanderthals.  For example, the Denisovan’s skull was probably significantly wider than that of modern humans’ or Neanderthals’. They likely also had a longer dental arch and no chin. Other anatomical features they compared were forehead height, facial protrusion, enamel thickness, dental arch length, molar size, cranial base size, palate height and width and anterior mandibular height.

The Denisovans were as tall as modern humans and taller than Neanderthals.

The lineage that developed into Denisovans and Neanderthals is estimated to have separated from the lineage that developed into “anatomically modern” Homo sapiens between 600,000 to 744,000 years ago. Denisovans and Neanderthals then significantly diverged from each other genetically a mere 300 generations after that. Several types of humans, including Denisovans, Neanderthals and related hybrids may have each dwelt in the Denisova Cave over thousands of years, but it is unclear whether they ever cohabited in the cave.

An international team of archeologists have been digging and exploring the various layers in the cave, which is refrigerator-cold even in the summer, for decades.

The HUJI researchers came to their conclusions after three years of intense work studying DNA methylation maps. The researchers first compared DNA methylation patterns among the three human groups to find regions in the genome that were differentially methylated.  Next, they looked for evidence about what those differences might mean for anatomical features – based on what’s known about human disorders in which those same genes lose their function.

“In doing so, we got a prediction as to what skeletal parts are affected by differential regulation of each gene and in what direction that skeletal part would change – for example, a longer or shorter femur bone,” Gokhman explained.

To test this ground-breaking method, the researchers applied it to two species whose anatomy is known: the Neanderthal and the chimpanzee.  They found that about 85% of their trait reconstructions were accurate in predicting which traits diverged and in which direction they diverged.  Then, they applied this method to the Denisovan and were able to produce the first reconstructed anatomical profile of the mysterious Denisovan.

As for the accuracy of their Denisovan profile, Carmel shared, “One of the most exciting moments happened a few weeks after we sent our paper to peer-review.  Scientists had discovered a Denisovan jawbone!  We quickly compared this bone to our predictions and found that it matched perfectly. Without even planning on it, we received independent confirmation of our ability to reconstruct whole anatomical profiles using DNA that we extracted from a single fingertip.”

In their Cell paper, Carmel and his colleagues predict many Denisovan traits that resemble Neanderthals’, such as a sloping forehead, long face and large pelvis, and others that are unique among humans, for example, a large dental arch and very wide skull.  Do these traits shed light on the Denisovan lifestyle? Could they explain how Denisovans survived the extreme cold of Siberia?

“There is still a long way to go to answer these questions but our study sheds light on how Denisovans adapted to their environment and highlights traits that are unique to modern humans and which separate us from these other, now extinct, human groups,” Carmel concluded.

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