Our DNA contains the functional instructions for all of our cells, from the cells in our brains to the cells in our bones and our blood. But it is only by activating and deactivating different segments of our DNA, or our genes, that our cells take on their specialized functions.
This is true for all sorts of organisms, whose cells are differentiated when different genes are switched on and off. In simple organisms, these on-off “switches” are typically situated only a short distance away from the genes that they activate and deactivate. But in complex organisms, these switches are sometimes separated from the genes that they regulate by long lines of DNA letters, sometimes numbering in the tens of thousands.
Recent research has found, however, that this long-distance form of gene regulation is actually a lot older than once thought. Published today in Nature, the research reveals that these distant on-off switches likely appeared early on in the evolution of animals, around 700 million years to 650 million years ago, or about 150 million years earlier than previously estimated.
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Switching Distant Genes On and Off
For long-distance gene regulation, or distal regulation, to work, DNA has to be folded or furled into intricate loops. These loops situate separated segments of DNA closer together in 3D space, enabling on-off switches to control genes that are technically tens of thousands of DNA letters away.
For a long time, it was hypothesized that this ability arose in animals that appeared around 500 million years ago, helping them specialize their cells for specific functions. But the new Nature research has indicated that distal regulation originated even earlier than that, likely in the common ancestor of all the animals that are alive today.
“This creature could repurpose its genetic toolkit in different ways like a Swiss knife, enabling it to refine and explore innovative survival strategies. We did not expect this layer of complexity to be so ancient,” said Iana Kim, the lead study author and a researcher at the Spanish Centre for Genomic Regulation (CRG) and the Centro Nacional de’Anàlisis Genòmica (CNAG), according to a press release.
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Dating the Origins of Distant Gene Switches
To trace this innovation back in time, the authors of the new study looked at the gene regulation mechanisms in 11 separate species. Some of these species came from early animal lineages, like the ctenophores, the poriferans, the placozoans, and the cnidarians. These lineages, which contain the comb jellies, the sea sponges, and other ocean creatures such as jellyfish, corals, and sea anemones, comprise some of the Earth’s simplest animals. Other species came from lineages of single-celled organisms that share a common ancestor with all animals today.
“You can discover a lot of new biology by looking at weird sea creatures. So far, we had been comparing genome sequences, but thanks to new methods we can now [analyze] which gene regulation mechanisms control genome function across species,” said Arnau Sebe-Pedrós, another study author and a group leader at the CRG, according to the release.
Indeed, a new method called Micro-C allowed the study authors to make 3D maps of the DNA of each of the 11 species, which followed the folds of their DNA sequences. While the loops of long-distance gene regulation didn’t appear in the DNA maps of the single-celled organisms, they did appear in the maps of the ctenophores, the placozoans, and the cnidarians, suggesting an origin of distal regulation some 700 million to 650 million years ago.
Surprisingly, the study authors also determined that different proteins help structure the DNA loops of different animals. While the looping of later animal lineages (like fish, amphibians, reptiles, birds, and mammals) is organized by CTCF, a protein that helps order different genes into different DNA segments, the loops of earlier animals (like the ctenophores) are organized by a separate protein from the same protein family.
“It is impressive that the same problem has been solved using different tools. Thanks to this work, we now know that you can use two different proteins to bring distal DNA [pieces] together in space forming a loop,” said Marc A. Marti-Renom, another study author and a group leader at the CRG and CNAG, according to the release.
The study authors stress that their research helps track the evolution of genomic regulation and provides practical insights into the regulatory mechanisms that control cell functions in humans and animals alike.
Read More: This Predatory Jellyfish Lived Before Plants Had Even Evolved
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Sam Walters is a journalist covering archaeology, paleontology, ecology, and evolution for Discover, along with an assortment of other topics. Before joining the Discover team as an assistant editor in 2022, Sam studied journalism at Northwestern University in Evanston, Illinois.
