Microbes offer insight on DNA folding

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Scientists’ findings on how ancient microbes store their genomes may shed light on how more complex organisms came to pack their DNA.

According to new research from several institutions, microbes called archaea microbes fold their DNA very similarly to eukaryotes, such as animals and plants. The study suggests that this particular DNA structure of archaea, which evolved an estimated 2.5 billion years ago, may be ancestral to eukaryotic DNA folding. The scientists published their findings in Science on Aug. 11.

Eukaryotes have a defined nucleus containing their genetic information and store their DNA by winding it tightly around proteins called histones. This forms dense structures called nucleosomes, making it easier for organisms to pack more and more DNA, which became a necessity as eukaryotic genomes grew larger.

“Genetic material is so huge that it’s very difficult to package the whole thing inside a cell,” said Sudipta Bhattacharyya, UT postdoctoral researcher fellow in molecular biosciences and co-first author of the paper Sudipta Bhattacharyya. “In each living organism, they have to have their own strategy to pack this genetic information.”

This folding is conserved among all eukaryotes, from fungi to humans, implying that it originated in a common ancestor. However, scientists were unsure of what exactly this ancestor was. Previous research by John Reeve, professor of microbiology at Ohio State University and co-author of the study, indicated that archaea also have histones, but their function was not known. According to Bhattacharyya, his team of researchers set out to see how these microbes packaged their DNA.

Researchers in the study examined these structures by first creating crystals holding DNA-histone complexes from a species of archaea that lives in extremely hot temperatures. X-ray crystallography allowed scientists to determine the three-dimensional structure of the DNA-histone complexes, said Francesca Mattiroli, postdoctoral researcher at the University of Colorado Boulder and co-first author of the study. The calculated structures were validated in another species of archaea after creating mutations that disrupted the DNA-histone structure and observing that the cells could not function properly.

They found that DNA in archaea represented a primitive way of structuring genetic material by bending around a column of histones, similar to eukaryotes. The researchers also found that archaea only use one type of histone while eukaryotes use four.

“These ancient structures look very similar to the DNA complexes of humans,” Bhattacharyya said. “Knowing this structure, this sheds light on how this DNA-protein complex actually evolved from those ancient structures.”

Next, researchers will look at how these DNA-histone complexes form in archaea and the mechanism behind archaeal gene expression.

Additional structural studies on eukaryotic gene expression could lead to advances in the field of drug discovery, Bhattacharyya said. According to Mattiroli, a vital point for future research is how eukaryotic DNA structure evolved from its precursor.

“How do these histone-DNA complexes form inside the cell? What controls the size of these complexes?” Mattiroli said. “Most importantly, how did we get from these structures to the nucleosome that is present in all eukaryotes? This will tell us how the modes of organizing DNA in our cells have evolved.”