Uncovering Clues to a Natural Gene-Editing Technique

Most evolutionary change happens slowly, over many generations. Through a process called natural selection, random genetic mutations that give individuals a survival advantage are passed on to their descendants, and the species gradually evolves. But sometimes, evolution has an accelerated timeline and a gene changes very quickly, likely in response to sudden environmental change. One cause of accelerated evolution is a type of mechanism called a diversity-generating retroelement (DGR).

DGRs are found in the genomes of microorganisms across the globe—from the arctic permafrost to Yellowstone’s hot springs and the human gut. DGRs can reverse-transcribe RNA back to DNA in a form of natural gene-editing. This process speeds up the evolution of proteins to help microorganisms adapt to changing environments.

Marine Biological Laboratory (MBL) Assistant Scientist Blair Paul is a co-author on a new paper published in Nature that sheds light on this process. The study deepens our understanding of the evolutionary origin of DGRs, and may be applicable to future gene-editing techniques.

Paul collaborated with Partho Ghosh’s lab at the University of California, San Diego, which figured out the first steps of this accelerated evolution by visualizing the relevant proteins and RNA in DGRs using cryogenic electron microscopy. They found that RNA especially controlled accelerated evolution, forming structures that started, maintained and stopped the process at the right place. These RNA structures, which were identified in the DGRs of many microorganisms, limited accelerated evolution to proteins needed for adaptation while protecting other essential proteins from harm.

“Prior to this, we really didn’t know much about the structural function of the RNA in a DGR,” Paul said. “We knew next to nothing about it.”

Paul compared their model DGR with roughly 300 other bacterial and archaeal DGRs. He found that about 75 percent of these DGRs shared structural RNA features with the model.

“It’s possible these RNA features first appeared in DGRs in common ancestors, rather than independently evolving in different bacteria,” Paul said. “But it’s hard to say: we just get this one snapshot in time."

Paul’s research group is studying DGRs at the MBL, particularly in multicellular cyanobacteria. Studies like this one could potentially help scientists engineer DGRs for applications like directed evolution or gene-editing technologies.

“Without these structural insights about how the RNA actually coordinates this, you may face limitations in trying to engineer this system,” Paul said.

Citation: Handa, S., Biswas, T., Chakraborty, J., Ghosh, G., Paul, B., & Ghosh, P. (2025). RNA control of reverse transcription in a diversity-generating retroelement. Nature, DOI: 10.1038/s41586-024-08405-w