There was a rule of DNA. Bacteria didn’t get the memo

Your DNA was never created from scratch.

Think of it like a prescription – it’s been passed down from parent to child for countless generations, dating back to the first life on Earth 4 billion years ago. Changes and modifications accumulated along the way, but always copied from something that already existed.

This is one rule that has held throughout time: To make DNA, you need to copy existing genetic material.

Scientists have recently found a protein that breaks this rule.

A mechanism that no one has seen before

“It was quite a surprise!” Alex Gao, a biochemist at Stanford University and senior author of the study, told DW.

His team was investigating how bacteria protect themselves from viruses when they identified something unexpected: a protein called Drt3b that makes DNA without copying itself. It uses its shape as a mold to put the right building blocks in the right place.

“We didn’t believe it until we saw the cryo-EM structure […] “That’s the moment it really caught on for us,” he said, referring to cryo-electron microscopy, a technique that images molecules at near-atomic resolution.

the conclusions were Published in Science Journal In April.

Scanning electron micrograph of Escherichia coli bacteria
Gao and his team used the bacterium E. coli. It is found in the intestines of humans and other warm-blooded animals and can also appear in soil and water after contamination. It is a cornerstone of research because of its rapid growth and simple, well-mapped genetics. This makes it the most widely used and best studied bacterial model organism.Image: NIH/Image Point FR/Image Alliance

So how does it actually work?

DRT3 – the entire system studied by Gao’s team – works in two phases.

DNA is double-stranded: think of it like a zipper, with its two sides fitting together.

One side is made in a familiar way, in which a protein called Drt3a uses a small piece of genetic material as a template to create a strand.

The other side is where things get weird. A second protein, Drt3b, needs to make the other side of that zipper—but it does so without a template. Instead, specific parts of the protein themselves act as guides, locking in place the correct DNA building blocks or “nucleotides” one by one until the strand is completed. And this is something we didn’t think was possible – at least not like this.

Other proteins have done something similar before – but only in small pieces, like writing a sentence. Drt3b writes a complete paragraph. It is the first known protein that produces a long, sequence-specific strand of DNA using something other than its structure as a guide.

How does it matter?

“This research is unprecedented,” says Philip Kranzush, a biochemist at Harvard Medical School who was not involved in the study.

That’s because scientists have been studying DNA since the 1950s and bacteria have been quietly doing something they never imagined. Which begs the question: what else are we missing?

There is a practical aspect to this also. If scientists can engineer Drt3b to produce other DNA sequences, it could one day serve as a tool for building custom DNA molecules — without needing a template to copy.

But we are not there yet. “We don’t know yet whether it can be reprogrammed or engineered in a useful way,” Rafael Pinilla-Redondo, an assistant professor in the microbiology section at the University of Copenhagen, told DW.

Francis Crick's letter to his son, March 19, 1953. It marks the revolutionary discovery of the structure and function of DNA. The letter shows a diagram of the double-helix structure of DNA.
Francis Crick, along with James Watson in 1953, helped uncover the structure of DNA, building on the important experimental work of Rosalind Franklin and Maurice Wilkins. He later proposed the “Central Dogma”, which states that genetic information flows from DNA to RNA to protein and that it does not flow back from protein to DNA.Image: UPI Photo/Imago

So does this break the laws of biology?

The discovery has sparked debate about the “central dogma of biology” – the idea that genetic information flows from DNA to RNA to protein, but never back from protein to DNA. If a protein can write a DNA sequence, does this break the rule?

“No, I wouldn’t say the central dogma has been broken,” Pinilla-Redondo says. The study shows that a protein helps create a short, repetitive DNA sequence in a very specific context—not proteins that typically rewrite the genetic code. “The exciting thing is not that the laws of biology have collapsed. It’s that evolution has found a very unexpected way of making DNA molecules,” he said.

But what does DNA actually do?

Scientists don’t know completely yet.

The leading hypothesis is that DNA acts as a kind of molecular sponge – soaking up essential components of the invading virus and inactivating it. But Gao is careful about how strongly he holds that view. “This is our leading hypothesis at present, but we are certainly open to alternative models,” he said.

Pinilla-Redondo agrees that the mechanism is still far from understood. He said, “Is DNA a hoax, a signal, a scaffold or a toxic molecule? That is the main mystery.”

Germany Frankfurt 2016 | Jennifer Doudna and Emmanuelle Charpentier with the Paul Ehrlich Award
CRISPR stores fragments of viral DNA and uses them to recognize and destroy invaders. It works like a guided pair of scissors: a short RNA sequence guides an enzyme to a matching section of DNA, where it is precisely cut. Jennifer Doudna and Emmanuelle Charpentier were awarded the 2020 Nobel Prize in Chemistry for turning this mechanism into a gene-editing tool. What makes CRISPR extraordinary is its speed, accuracy and simplicity, allowing scientists to rewrite the DNA in almost any organism – and transforming modern biology.Image: Alexander Heinl/dpa/Picture Alliance

Is this the next CRISPR?

CRISPR – the scissors that allow scientists to cut and edit DNA with unprecedented precision – was first discovered as a bizarre bacterial defense system. Since then it has transformed medicine, including first approved gene therapyFor sickle cell disease in 2023.

Sounds familiar, doesn’t it? But will it be a similar story with DRT3?

Probably not – at least not yet. “CRISPR is a once-in-a-generation breakthrough that has revolutionized biotechnology,” says Gao. “Although it is too early to predict the applications of DRT3, we are most excited about DRT3 expanding our understanding of the mechanisms of DNA synthesis.”

A glimpse of microbial dark matter

“The field of bacterial immunity is exploding,” says Pinilla-Redondo. Experimental research on these bacterial defense systems has just begun – and the diversity of mechanisms uncovered is astonishing, with many research groups around the world independently coming to similar conclusions.

For Alex Gao’s team, this discovery is less an end than a beginning. Bacteria have spent billions of years fighting viruses, quietly developing molecular tricks that we are just beginning to discover. How many more people are there?

Gao concluded: “This points to a vast reservoir of uncharacterized biology within microbial ‘dark matter’, where fundamental mechanisms likely remain undiscovered.”

Edited by: Frank Lee

Source link

Leave a Comment