DNA unravelled: X-rays show archaic folding origin

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  • Published: Aug 15, 2017
  • Author: David Bradley
  • Channels: X-ray Spectrometry
thumbnail image: DNA unravelled: X-rays show archaic folding origin

Ancient folding problem

Archaea wrap their DNA (yellow) around proteins called histones (blue), shown above in a 3-D representation. The wrapped structure bears an uncanny resemblance to the eukaryotic nucleosome, a bundle of eight histone proteins with DNA spooled around it. But unlike eukaryotes, archaea wind their DNA around just one histone protein, and form a long, twisting structure called a superhelix. Credit: Francesca Mattiroli

New X-ray crystallographic work by scientists at the Howard Hughes Medical Institute reveals that organisms with cell nuclei, eukaryotes, which includes all multicellular life uses proteins to pack its DNA into the cell nucleus using similar folding techniques as that seen in microbes whose ancestry stretches back to the dawn of life on earth, the archaea.

A diverse range of organisms from palm trees to panthers, haricot beans to human beings, as well as some single-celled microorganisms, all fold their DNA in the same way to allow them to pack their genome into the nucleus of the cell as efficiently as possible. Karolin Luger of the HHMI and the University of Colorado Boulder and her colleagues report X-ray diffraction work on the three-dimensional structure of proteins bound to DNA in a class of microbes known as archaea. "If you look at the nitty gritty, it's identical," Luger explains. "It just blows my mind."

Crystal solution

This DNA folding in archaea, which the team reports in the journal Science suggests that there is a single evolutionary origin to genome folding that was shared by an ancestor of the archaea and eukaryotes alike. The folding pattern is remarkably well conserved across all eukaryotes, the team says. Eukaryotes have a defined cell nucleus surrounded by a membrane. The eukaryotes, bacteria, and archaea represent the three domains of all life on earth. However, scientists think that the lineage of archaea stretches back further than any other living organism to a primordial ancestor that was the first to evolve a mechanism for folding its DNA.

DNA is wound around a protein complex comprising eight histone proteins to form the nucleosome, these are then strung together on a strand of DNA like beads on a string. The fact that molecular necklace is universal suggests that it emerged very early in the history of life on earth. If all eukaryotes fold their DNA in the same way then, team member John Reeve, a microbiologist at Ohio State University, explains, it must have evolved in a common ancestor. "But, what that ancestor was, is a question no-one asked," Reeve says.

In his previous studies, Reeve had demonstrated that histone proteins are present in the cells of archaea. However, archaea are prokaryotes, microorganisms that have no well defined nucleus. There was thus an apparent paradox. Why were those DNA folding histones present at all as there is no necessity for packing the DNA into a membrane-bound nucleus as is the case with eukaryotes it seems. The team examined the detailed structure of hard-won crystals containing DNA bound to archaeal histones of the thermophilic microbe Methanothermus fervidusto find a solution.

Historic histones

Ultimately, their X-ray structure showed that despite this microbe using a single type of histone and not the four used by eukaryotes, the process of DNA folding was very similar, showing the same kinds of bends as are found in eukaryotic nucleosomes. There was a difference though. Instead of their being individual protein beads hanging on a DNA string, the archaeal DNA formed a long superhelix, a single, large coil of already twisted DNA strands. "In Archaea, you have one single building block," Luger explains. "There is nothing to stop it. It's almost like it's a continuous nucleosome, really."

The team explains that the formation of this superhelix is a particularly significant step in DNA folding. When the researchers generated mutations that interfered with the formation of the structure they found that the cells were not able to grow well under stressful conditions. Moreover, the cells were incapable of utilizing all of their genes in the normal way to express proteins.

Although there is no doubt that archaeal DNA folding represents the earliest folding process, some questions remain. For instance, where is the nucleosome-like structure that bridges the gap between the simple archaeal fold and the elaborate nucleosome found in eukaryotes.

Related Links

Science 2017, online: "Structure of histone-based chromatin in Archaea"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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