Incredible system for modifying DNA in animals discovered

(ORDO NEWS) — Your DNA, or deoxyribonucleic acid, is a molecule made up of two long strands of nucleotides that wrap around each other to form a double helix. It is the hereditary material of humans and almost all other organisms that carries the genetic instructions for development, function, growth and reproduction.

Almost every cell in the human body has the same DNA. Most DNA is found in the nucleus of the cell (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).”

DNA contains the blueprint that your body is built to, but it’s a living document: Adjustments to the design can be made by epigenetic marks. The study of these marks and how they work is important for understanding biology and genetics, and for developing treatments for diseases and disorders.

In humans and other eukaryotes, two main epigenetic marks are known. But a team from the University of Chicago has discovered a third, new epigenetic mark – previously known only in bacteria – in small freshwater animals called bdelloid rotifers.

This fundamental and surprising discovery was reported on February 28, 2022 in the journal Nature Communications.

“We found back in 2008 that bdelloid rotifers are very good at grabbing foreign genes,” says senior study author Irina Arkhipova, senior researcher at the Josephine Bay Paul Center of the Marine Biological Laboratory. “We found that rotifers, about 60 million years ago, accidentally picked up a bacterial gene that allowed them to introduce a new epigenetic mark that didn’t exist before.”

Jumping genes

Epigenetic marks are modifications of DNA bases that do not change the basic genetic code, but overwrite it with additional information that can be inherited along with the genome.

Epigenetic marks typically regulate gene expression by turning them on or off, especially in the early stages of development or when the body is under stress. They can also suppress transposons, or “jumping genes,” which can threaten the integrity of your genome.

The discovery marks the first time that a horizontally transferred gene – that is, a gene acquired from another organism other than through sexual reproduction – has been shown to alter the gene regulation system in eukaryotes.

“This is very unusual and has not been reported before,” Arkhipova said. “It is believed that horizontally transferred genes are predominantly operational genes, not regulatory ones. It is difficult to imagine how a single horizontally transferred gene can form a new regulatory system, because existing regulatory systems are already very complex.”

“It’s almost unbelievable,” says Irina Yushenova, co-author of the first study, a researcher at Arkhipov’s lab.

Yushenova explained how this process was supposed to take place: “Try to imagine that somewhere in the distant past, a piece of bacterial DNA joined with a piece of eukaryotic DNA. Both of them joined in the rotifer genome and formed a functional enzyme.

This is not so easy to do even in the laboratory “and then it happened naturally. And then this compound enzyme created this amazing regulatory system, and the bdelloid rotifers could start using it to control all these hopping transposons. It’s like magic.”

Transposons – a term for genes that move from place to place within the genome – can change the genetic code for better or worse, so keeping them under control is very important.

“You don’t want transposons jumping around your genome,” said first author Fernando Rodriguez, also a researcher at Arkhipova’s lab.

They can mess things up, so you want to keep them under control.” And the epigenetic system for achieving this goal varies from animal to animal. In this case, horizontal gene transfer from bacteria to bdelloid rotifers has created a new epigenetic system in animals that has not been described before.” .

“Bdelloid rotifers, in particular, need to keep their transposons in check because they reproduce mostly asexually,” says Arkhipova.

Asexual lines have less means to suppress the spread of harmful transposons, so adding an extra layer of protection can prevent mutational collapse. Indeed, transposon abundance in bdelloids is much lower than in sexual eukaryotes, which do not have this additional epigenetic layer in the genome defense system.

In two previously known epigenetic marks in eukaryotes, a methyl group is added to the DNA base, either cytosine or adenine.

The team’s recently discovered mark is also a modification of cytosine, but with a distinct bacterial arrangement of the methyl group – essentially repeating evolutionary events more than two billion years ago when common epigenetic marks arose in early eukaryotes.

Bdelloid rotifers are extremely hardy animals, as found out over the years in the laboratory of Arkhipova and David Mark Welch at MBL. They can dry out completely for weeks or months and then come back to life when water appears. During the dry phases, their DNA breaks down into many fragments.

“When they rehydrate or otherwise expose the ends of their DNA, this could be an opportunity for the transfer of foreign DNA fragments from ingested bacteria, fungi or microalgae into the rotifer genome,” says Arkhipova. As it turned out, about 10 percent of the rotifer genome comes from non-metazoic sources.

However, Arkhipova’s lab was surprised to find in the rotifer genome a gene similar to bacterial methyltransferase (methyltransferase is a type of molecule that catalyzes the transfer of a methyl group in DNA). “We hypothesized that this gene gives us a new transposon suppression function, and have spent the last six years to prove that this is indeed the case,” says Arkhipova.

It is still too early to talk about the implications of the discovery of this new epigenetic system in rotifers. But parallel discoveries had a great impact on biology.

“A good comparison is the CRISPR-Cas system in bacteria, which started out as a discovery in basic research. CRISPR-Cas9 is now used ubiquitously as a gene-editing tool in other organisms,” Rodriguez said. “This is a new system. Will it have applications, implications for future research? It’s hard to say yet.”

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