A team of researchers from Israel and Spain has produced reconstructions of Denisovans, an extinct sister group of Neanderthals, based on patterns of methylation — chemical changes — in their ancient DNA.
A portrait of a juvenile female Denisovan based on a skeletal profile reconstructed from ancient DNA methylation maps. Image credit: Maayan Harel.
“We provide the first reconstruction of the skeletal anatomy ofDenisovans. In many ways, they resembled Neanderthals, but in some traits, they resembled us, and in others they were unique,” said senior author Dr. Liran Carmel, a researcher with the Hebrew University of Jerusalem.
Dr. Carmel and his colleagues came to their conclusions after three years of intense work studying DNA methylation maps.
DNA methylation refers to chemical modifications that affect a gene’s activity but not its underlying DNA sequence.
The scientists 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.
“By doing so, we can get 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,” said lead author Dr. David Gokhman, also from the Hebrew University of Jerusalem.
To test this ground-breaking method, the team applied it to two species whose anatomy is known: the Neanderthal and the chimpanzee.
They found that roughly 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.
The authors identified 56 anatomical features in which Denisovans differed from modern humans and/or Neanderthals, 34 of them in the skull.
For example, the Denisovan skull was probably wider than that of modern humans or Neanderthals. They likely shared Neanderthal traits such as an elongated face and a wide pelvis. They also had an increased dental arch and lateral cranial expansion.
“One of the most exciting moments happened a few weeks after we sent our paper to peer-review,” Dr. Carmel said.
“Scientists had discovered aDenisovan 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.”
Anatomical comparison of modern human, Neanderthal and Denisovan skeletons. Image credit: Maayan Harel.
The findings show that DNA methylation can be used to reconstruct anatomical features, including some that do not survive in the fossil record. The approach may ultimately have a wide range of potential applications.
“Studying Denisovan anatomy can teach us about human adaptation, evolutionary constraints, development, gene-environment interactions, and disease dynamics,” Dr. Carmel said.
“At a more general level, this work is a step towards being able to infer an individual’s anatomy based on their DNA.”
The team’spaperwas published in the journalCell.
David Gokhmanet al. 2019. Reconstructing Denisovan Anatomy Using DNA Methylation Maps.Cell179 (1): 180-192; doi: 10.1016/j.cell.2019.08.035