Understanding Evolution

New twists on ancient DNA

October, 2019

Credit: Flickr Member Geoff Hutchison

DNA looks like a delicate molecule: a narrow twisted ladder, perhaps two inches long, but just two nanometers wide. What would it take to destroy such a thin chain of atoms? More than one might think! Researchers have calculated that under common conditions, it would take more than 500 years for half of the chemical bonds in a molecule of DNA in bone to disintegrate — and under ideal conditions, it could survive much longer. This surprising sturdiness underlies the field of ancient DNA, which has so far managed to reconstruct genetic sequences from samples up to 700,000 years old (in the case of an ancient horse frozen in permafrost). Of course, such information provides a fascinatingly detailed glimpse of evolutionary history, revealing for example that humans and Neanderthals interbred, as well as which human gene versions came to us from our Neanderthal ancestors. This past month, two new studies highlighted how we can squeeze even more genetic information out of ancient remains.

Where's the evolution?

One group of researchers used the fact that DNA encodes proteins, which are sturdier than DNA, to learn about the genetics and evolution of ancient rhinos. While not every change in DNA translates into a protein change, the reverse is true: every difference in the amino acid sequence of two proteins indicates that there was a difference in the DNA sequences that encoded them. So if we can recover proteins from ancient remains and sequence them, we can glean information about the organism's genetic sequence — and, we hope, about its evolution. Previous studies of ancient proteins mostly focused on a very abundant protein (collagen) that is not very useful for studying recent evolution because it evolves so slowly.

Drawing of the woolly rhinoceros, Coelodonta antiquitatis. Credit: Wikipedia

In the new research, biologists recovered six different proteins from the enamel of a 1.77 million year old rhinoceros tooth, the DNA of which had long since degraded. The scientists then figured out the amino acid sequence of the proteins using a technique called mass spectrometry and compared the ancient amino acid sequences to those of the same proteins from other rhinos (all living species and two that went extinct much more recently, and thus, for which DNA is preserved). The sequences supported the ideas that the 1.77 million year old rhino was more closely related to the other two recently extinct species than to any living rhino and that the ancestral rhino had just a single horn. But more importantly, the research demonstrated that proteins can be an important source of genetic information for ancient samples too old or preserved in the wrong conditions from which to recover DNA. Teeth are common in the fossil record, and studying their proteins could solve evolutionary puzzles when DNA clues to those mysteries have already broken down.

Other recent research focused on how to get even more information out of ancient DNA when it is preserved. Many paleontologists study the shapes of fossils to learn about long extinct species, but for the ancient human lineage, the Denisovans, there just isn't a lot of shape to study. We have only so far discovered a few teeth, a jawbone, and a single finger bone from this extinct hominin. Luckily, the ~75,000 year old finger bone has yielded a wealth of genetic information, and we have the complete genome of the Denisovan girl to whom this bone belonged. It is ironic to know so much about the genetics of a long extinct species, while knowing so little about what they looked like!

To change that, scientists developed a new method for forming hypotheses about anatomy based on DNA evidence. The method relies on methylation, a cellular process in which methyl groups (a single carbon atom bound to three hydrogen atoms) are added to a DNA molecule. This usually has the effect of turning genes "off" or "down" (i.e., so that a protein-coding gene produces less of its protein than it otherwise would). As it happens, methylated and unmethylated DNA regions decay in different ways, so scientists could reconstruct which parts of the Denisovan genome were methylated. They could also compare these patterns to the methylation patterns in modern humans and chimpanzees, as well as in ancient Neanderthals.

An artist's reconstruction of a Denisovan girl. MAAYAN HAREL Credit: Science

However, these comparisons still didn't reveal how turning on or off different genes might affect anatomy. To get that information, scientists turned to a database that collects information about human mutations in various genes, the diseases they cause, and the anatomical effects of these diseases. Most of these mutations cause the affected gene to become completely dysfunctional and result in various anatomical quirks — for example, a wide jaw or a narrow pelvis. The biologists reasoned then that, for example, turning "down" a gene in a Denisovan (via methylation) might have a similar (if dampened) anatomical effect to turning off the gene (via mutation) in a modern human.

The scientists figured out where the human, Neanderthal, and Denisovan genomes had strikingly different patterns of methylation and looked to the disease database to hypothesize about how those different methylation patterns might affect anatomy. Their analysis suggested that, like Neanderthals, Denisovans had a low forehead and wide pelvis, but had a wider face than either humans or Neanderthals, among other traits. To test whether their hypotheses about the Denisovans' appearance were likely to be correct, the researchers tried to use the method to "predict" the physical traits of Neanderthals (which we already know from an abundance of fossils) and of chimpanzees (known from direct observation). A further test was provided when a new Denisovan fossil (the jawbone mentioned previously) was discovered. The methylation method performed well; it did a good a job "predicting" the traits of Neanderthals and chimps, and the scientists' hypotheses about the Denisovan jaw were a match for the new fossil.

While there is still a lot to learn about Denisovan anatomy, it is exciting to have a new way to learn about this lineage so closely related to our own — and it will be interesting to see what we learn about other extinct lineages for which DNA happens to be preserved. And if not? Well, perhaps their proteins, like those of ancient rhinos, will have something to tell us instead. But most intriguing of all is simply the knowledge that these techniques are ones that scientists could not have dreamed of 50 years ago. Fifty years from now, what other evolutionary secrets will we be able to pry from fossils? We are eager to find out.

Primary literature

  • Cappellini, E., Welker, F., Pandolfi, L., Ramos-Madrigal, J., Samodova, D., Rüther, P. L., ... Willerslev, E. (2019). Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny. Nature. DOI: https://doi.org/10.1038/s41586-019-1555-y read it
  • Gokhman, D., Mishol, N., de Manuel, M., de Juan, D., Shuqrun, J., Meshorer, E., ... Carmel, L. (2019). Reconstructing Denisovan anatomy using DNA methylation maps. Cell. 179: 180-192. read it

Discussion and extension questions

  1. Imagine that a friend claims that scientists have decoded the DNA of Tyrannosaurus rex and plan to recreate this animal using genetic engineering. From a technical standpoint, does this seem likely to be true? How would you respond?
  2. In your own words, describe how and why genetic information can be gleaned from proteins (which are not DNA).
  3. Why do scientists have a good understanding of Neanderthals’ anatomical features, but not Denisovans'?
  4. Imagine that you are a biologist studying the Denisovan genome. In a particular region, the Denisovan genome is heavily methylated and the modern human genome is not. You do some research in the scientific literature and find out that some scientists have traced a particular disease syndrome to mutations in this region. One of the traits associated with this disease is unusually widely spaced eyes. Based on this information what hypothesis would you propose about Denisovan facial features? Explain your reasoning.
  5. Advanced: Read this news article and updates about the initial analyses of the Denisovan finger bone from May 2010. Based on the article above, what additional discoveries have we made about the Denisovans since 2010? Describe at least three, including any corrections you would make to the 2010 article.


  • Allentoft, M. E., Collins, M., Harker, D., Haile, J., Oskam, C. L., Hale, M. L., ... Bunce, M. (2012). The half-life of DNA in bone: measuring decay kinetics in 158 dated fossils. Proceedings of the Royal Society B. DOI: https://doi.org/10.1098/rspb.2012.1745
  • Cappellini, E., Welker, F., Pandolfi, L., Ramos-Madrigal, J., Samodova, D., Rüther, P. L., ... Willerslev, E. (2019). Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny. Nature. DOI: https://doi.org/10.1038/s41586-019-1555-y
  • Gokhman, D., Mishol, N., de Manuel, M., de Juan, D., Shuqrun, J., Meshorer, E., ... Carmel, L. (2019). Reconstructing Denisovan anatomy using DNA methylation maps. Cell. 179: 180-192.


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