04/05/2026
The Molecular Breakthrough :How a protein writes DNA code
For decades, biology taught us a simple rule: genetic information flows in one direction, just like cars on a one-way street. First proposed by Francis Crick in 1958, the "Central Dogma" of molecular biology posits that information flows only from DNA to RNA, and from RNA to protein. As Crick wrote, "...the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible." Until now, this has been the fundamental law of the field.
Interestingly, a groundbreaking discovery by a team from Stanford University recently found a strain of bacteria that can synthesize DNA from protein, running flatly contrary to this dogma. In the canonical process of synthesizing DNA or RNA, a template strand is required. A polymerase enzyme then creates complementary strands using dNTPs. While reverse transcriptase enzymes can synthesize DNA from single-stranded RNA templates, the Stanford team, led by Hyunbin Lee, found that a bacterial enzyme can synthesize a long, repetitive DNA sequence without any nucleic acid template, using its own structure as a guide.
The discovered system, DRT3, is a defense-associated reverse transcriptase consisting of three parts: DRT3a and DRT3b (which are reverse transcriptases) and a non-coding RNA. Using cryo-electron microscopy, the team observed that the complex contains six copies of each component arranged symmetrically. While DRT3a follows the traditional route by using a small piece of non-coding RNA as a template, DRT3b provided the big surprise. It possesses key amino acids in its active site that mimic a template, guiding which bases are added one after another in an entirely unexpected way.
“The protein itself serves as the blueprint for the DNA sequence,” senior author Alex Gao told Science. “That was quite a surprise,” he said, adding, “This is a fundamentally new way that life produces DNA.”
Consequently, the usual semi-conservative rule of DNA synthesis is not followed in the DRT3b pathway. The researchers confirmed this by isolating the DRT3a and DRT3b enzymes and placing them in a test tube with dNTPs. They observed that DNA was produced even when all traditional DNA/RNA templates were removed, proving the protein was the source of the information.
Using Next-Generation Sequencing (NGS) to read the resulting DNA strands, they found the sequences were highly specific (comprising AC and TG repeats). This confirmed that the synthesis was not random but followed a strict "code" provided by the protein's amino acid arrangement. Finally, to confirm the protein acted as the template, they altered specific amino acids within the DRT3b enzyme. When the protein "blueprint" was changed, the resulting DNA sequence changed accordingly, providing definitive proof.
What remains unclear is exactly how this unique system helps bacteria defend themselves against phages. Gao and his team suggest it could act as a “molecular sponge,” holding onto phage components to either trigger an immune response or render the phage functionless.
It is amazing to consider that for nearly 70 years, every experiment reinforced Crick’s vision of a one-way flow of information. Now, we are faced with evidence that life has another trick up its sleeve. This discovery serves as a powerful reminder that the “rules” of biology are not always as set in stone as they seem.
References:
https://www.sciencealert.com/dna-can-be-built-in-a-way-weve-never-seen-before-study-finds
https://www.science.org/content/article/scientists-stunned-fundamentally-new-way-life-producesdna?fbclid=IwY2xjawRandVleHRuA2FlbQIxMQBzcnRjBmFwcF9pZAEwAAEeYsUFAG3RDhLFQvcXvJZspKnAMFg365rpll5Kv9lZNruXzxu0WddV6quYyiU_aem_jGoY4P5LDFaNzF2fsVFbCg
Deng et al., Science 10.1126/science.aed1656 (2026).
Written by: Ashfia Akter Sumaiya
Poster Credit: Adrita Afrin
Edited by: Anirban Maitra Abir
