WOODS HOLE, Mass. — Your DNA holds the blueprint for building your body, but it’s a living document: design adjustments can be made by epigenetic marks.
Epigenetic marks are changes to the bases of DNA that do not alter the underlying genetic code, but “write” over it additional information that can be inherited with your genome. Epigenetic marks typically regulate gene expression – turning genes on or off – especially during early development or when your body is under stress. They can also suppress ‘jumper genes’ – transposable elements that threaten the integrity of your genome.
In humans and other eukaryotes, two main epigenetic marks are known. A team from the Marine Biological Laboratory (MBL) has discovered a third novel epigenetic mark – once known only in bacteria – in bdelloid rotifers, small freshwater animals. This fundamental and surprising discovery is reported this week in Communication Nature.
“We found in 2008 that bdelloid rotifers are very good at capturing foreign genes,” said lead author Irina Arkhipova, senior scientist at MBL’s Josephine Bay Paul Center. “What we discovered here is that rotifers around 60 million years ago accidentally captured a bacterial gene that allowed them to introduce a new epigenetic mark that hadn’t existed before.” This is the first time that a horizontally transferred gene has been shown to remodel the gene regulatory system in a eukaryote.
“It’s very unusual and hasn’t been reported before,” Arkhipova said. “Horizontal transferred genes are thought to be preferentially operational genes, not regulatory genes. It is difficult to imagine how a single horizontally transferred gene would form a new regulatory system, because existing regulatory systems are already very complicated.
“It’s almost unbelievable,” said co-first author Irina Yushenova, a researcher in Arkhipova’s lab. “Just try to imagine, somewhere in time, that a piece of bacterial DNA was fused with a piece of eukaryotic DNA. The two joined together in the rotifer genome and they formed a working enzyme. It’s not that easy to do, even in the lab, and it happened naturally and then this composite enzyme created this amazing regulatory system, and the bdelloid rotifers were able to start using it to control all these let’s transpose jumpers. It’s like magic.
“You don’t want transposons jumping around your genome,” said first author Fernando Rodriguez, also a researcher in Arkhipova’s lab. “They’re going to mess things up, so you want to keep them under control. And the epigenetic system to accomplish that is different in different animals. In this case, horizontal gene transfer from bacteria to bdelloid rotifers created a new epigenetic system in animals which had not been previously described.
“Bdelloid rotifers, in particular, have to control their transposons because they mostly reproduce asexually,” Arkhipova said. “Asexual lines have less means to suppress proliferation of deleterious transposons, so adding an extra layer of protection could prevent mutational fusion. Indeed, transposon content is much lower in bdelloids than in bdelloids. sexual eukaryotes that lack this additional epigenetic layer in their genome defense system.
In the two previously known epigenetic marks in eukaryotes, a methyl group is added to a DNA base, either cytosine or adenine. The team’s newly discovered mark is also a modification of cytosine, but with distinct bacterial-like positioning of the methyl group – essentially recapitulating evolutionary events from over two billion years ago, when epigenetic marks conventional forms of the first eukaryotes emerged.
Bdelloid rotifers are extremely resilient animals, as the Arkhipova and David Mark Welch labs at MBL have discovered over the years. They can completely dry out (dry out) for weeks or months at a time, then come back to life when water becomes available. During their desiccation phases, their DNA breaks down into several pieces. “When they rehydrate or make their DNA ends accessible, this could be an opportunity for foreign DNA fragments from ingested bacteria, fungi, or microalgae to be transferred into the rotifer’s genome,” Arkhipova said. . About 10% of the rotifer’s genome comes from non-metazoan sources, they found.
Yet the Arkhipova lab was surprised to find a gene in the rotifer’s genome that resembled a bacterial methyltransferase (a methyltransferase catalyzes the transfer of a methyl group to DNA). “We hypothesized that this gene conferred this novel transposon-suppressing function, and we’ve spent the last six years proving that this is indeed the case,” Arkhipova said.
It is too early to know what the implications of the discovery of this new epigenetic system in rotifers might be. “A good comparison is the CRISPR-Cas system in bacteria, which started as a basic research discovery. Now CRISPR-Cas9 is being used everywhere as a gene-editing tool in other organisms,” Rodriguez said. “It’s a new system. Will it have applications, implications for future research? It’s hard to say.”
These findings open the door to new tools and research directions to study genome function and resilience in this rotifer system. In the future, this knowledge could be creatively applied to impact society in times of rapid environmental change.
The Marine biology laboratory (MBL) is dedicated to scientific discovery – exploring basic biology, understanding marine biodiversity and the environment, and informing the human condition through research and education. Founded in Woods Hole, Massachusetts in 1888, MBL is a private, nonprofit institution and a subsidiary of the University of Chicago.
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Bacterial N4-methylcytosine as an epigenetic mark in eukaryotic DNA
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