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There’s a war going on throughout our planet that’s older than humanity, older than complex life, and almost as old as life itself. For billions of years, bacteria have squared off against their natural nemesis—viruses known as bacteriophages, or just phages—in an evolutionary arms race to try to outsmart the enemy.
Now a new study in the journal Science details a devilishly devious bacterial strategy to thwart phages through self-replicating DNA. Typically, DNA is copied from a template as one enzyme unzips a double helix while another enzyme, or polymerase, assembles nucleotides to create a new DNA strand. However, a Stanford University team discovered that bacteria can actually circumvent this rule and create a repetitive DNA sequence without a nucleic acid template by just using itself as the guide.
“The protein itself serves as the blueprint for the DNA sequence,” Stanford University biochemist Alex Gao, senior author of the study, told Science. “This is a fundamentally new way that life produces DNA.”
The team specifically examined DRT3, a bacterial defense complex found in Escherichia coli, and showed that it consists of two reverse-transcriptase enzymes, Drt3a and Drt3b, together with a non-coding RNA—an RNA molecule that isn’t translated into protein. Their attention centered on Drt3b, which, as Science reports, carries amino acids in its active site, the pocket where substrate molecules undergo chemical reactions.
This created a self-contained system that produced a repeating adenine-cytosine (AC) motif. Crucially, this is just a repetitive sequence and not a completely new way to write new DNA sequences, but it represents a major shift in our perception of how life can write these sequences.
“This is not a protein ‘reading’ itself to create a complex message; rather, it is a highly specialized structural constraint,” Northeastern University’s Nikolai Slavov, a chemical biologist who is unaffiliated with the study, wrote on LinkedIn. “The protein is essentially a ‘stuttering’ machine, physically keyed to produce a simple, repetitive sequence.”
So why make this repetitive sequence at all? The answer isn’t yet entirely clear, but according to Science, it’s likely that these sequences act as “molecular sponges” that somehow either interfere with the phage directly or create immune elements that allow the bacteria to recognize the viral infection. Gao tells Science that further investigation of the all-in-one molecular machine Drt3b may reveal ways to make other novel DNA sequences, which could help produce more advanced DNA hydrogels for use in drug delivery and as scaffolds for tissue regeneration.
Humans could soon be drawn even further into the ongoing war between bacteria and viruses because phages offer a possible line of defense against antimicrobial resistant (AMR) “superbugs”—bacteria who’ve evolved strategies against modern antibiotics. To overcome that threat, we’ll need learn every trick bacteria use to thwart our medicinal defenses.
Darren lives in Portland, has a cat, and writes/edits about sci-fi and how our world works. You can find his previous stuff at Gizmodo and Paste if you look hard enough.
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