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Have the Roles Been Reversed?
The central dogma of molecular biology implies that the expression of living things’ traits is through a one-way flow of information. This information flows from DNA to RNA to then produce a protein in charge of said trait expression. This article explores potential findings that could debunk this idea of a “one-way flow” by studying the reverse transcriptase protein, which uses an RNA Template to produce DNA. Another finding is the DRT3 protein, which contains a subunit called “Drt3b” that relies only on its own activity, with no RNA or DNA template, to produce a special DNA sequence.
HEALTHCAREGENETICSENVIRONMENTTRENDBIOLOGY
Mariam Hamdar
9/4/20265 min read
Introduction
For decades, understanding life on earth was a mystery among all notable scientists. This mystery became a central debate for years until Swiss physician Friedrich Miescher proposed that the secret behind all creatures’ physical appearance was embedded in every single cell in their body. Further research by Alfred Hershey and Martha Chase in 1952 confirmed that our cells carry genetic material (DNA). DNA is the body’s form of expression, as it codes for all physiological functions. This profound discovery shifted the question of “what expresses our human traits?” to “how does DNA express said traits?”
In 1957, Francis Crick put these questions to rest by proposing “The Central Dogma of Molecular Biology”. His proposition indicates that our genetic information undergoes a one-way flow through transcription and translation to then be expressed: DNA (deoxyribonucleic acid, genetic material found in cells) → RNA (ribonucleic acid, a single stranded molecule that transcribes from DNA) → protein (enzymes, hormones, neurotransmitters, antibodies, and transport proteins that are translated from RNA). What made Crick’s findings interesting is his stress on its “one-way flow”. Once the information is finalized into a protein it cannot turn into nucleic acid again (Sustar, 2007). That is, for years, science has believed that it is impossible for the Central Dogma to completely reverse all three steps, or for a protein to produce DNA. However, recent studies have forced us to ask the question: “Have the roles been reversed?”
Reverse Transcriptase
The first challenge that Crick’s “Central Dogma of Molecular Biology” faced was the discovery of the reverse transcriptase. This transcriptase is a protein that facilitates the reverse process of transcription, as it produces DNA from RNA.
Found in viruses that carry their genetic material as RNA like HIV, it helps in viral attacks. This protein’s mechanism is simple. The virus starts by releasing its RNA into the host cell (infected cell) along with said protein. In the host cell, the reverse transcriptase utilizes the virus’ RNA to produce from it a single stranded DNA molecule (complementary DNA, CDNA). Another DNA strand is synthesized from the complementary one. This results in a double stranded DNA molecule that integrates into the host’s genome (Lim D et.al, 1989).
The reverse transcriptase is found to be multifunctional as it also has a profound role in bacteria. To protect itself from viral attacks, bacteria contain specific sequences of DNA called “Retrons”. The Retron DNA sequence transcribes the non-coding RNA sequence (ncRNA).
The ncRNA will then utilize the reverse transcriptase to reverse transcribe DNA: multicopy single stranded DNA (msDNA). Thus, the process is summarized as: Retron DNA → transcription → Retron RNA (ncRNA) → reverse transcriptase → msDNA.
The msDNA and ncRNA will then bind together and form an unusual RNA-DNA hybrid. This Retron product will act as a sensor, detecting viral attacks in bacteria (Lim D et.al, 1989).
Although the reverse transcriptase breaks the “one-way flow” that Crick entailed, it was not found to be revolutionary to the Central Dogma. That is, the prior discovery of the DNA’s structure, which is said to be double stranded or double helix, has entailed that a set nucleic acid could produce another complementary set for it. This derivation was concluded after discovering the mechanism of DNA replication which happens through the help of the protein “DNA polymerase”.
The DNA is made out of 4 types of nucleic acid base pairs: A, T, C, and G. When replicating a DNA strand to produce its complementary one, the DNA polymerase will recognize A in the template (original) strand and add its complementary nucleic acid base pair T to the replicated strand. Thus, A is complementary to T and likewise, C is complementary to G.
RNA is also made out of nucleic acid, where A is complementary to U, and C is complementary to G. Thus, producing a complementary DNA strand from an RNA strand is not impossible as they both share nucleic acid base pairs that could be replicated.
If we circle back to Crick’s main claim, we realize that he stresses over the inability of a protein to turn back into nucleic acid. Thus, the reverse transcriptase expanded the central dogma as it showed that information is exchanged between DNA and RNA, rather than debunk it.
THE DRT3 PROTEIN
A recent discovery that further challenges our view of the central dogma of molecular Biology is the DRT3 gene. Discovered only in bacteria, it acts as a defense system by protecting them against viral attacks (Stone, 2026).
This protein is made out of 2 subunits: Drt3a and Drt3b. We observe that the Drt3a subunit is usual, as it uses a non-coding RNA sequence and a reverse transcriptase. Through this RNA template, it produces a repetitive DNA sequence made out of G and T nucleotides. However, scientists were taken back when studying the Drt3b subunit. Found to have no RNA or DNA template and no other protein that helps in copying, like the reverse transcriptase or DNA polymerase, this subunit works purely on its own. The Drt3b uses its own built-in activity in its active site to produce a repetitive DNA sequence made out of A and C nucleotides.
As both produced strands are complementary to each other, they bind together and produce a double helix DNA molecule that does not integrate into the bacteria’s genome, but is purely there for an immune defense (Sarfaraz k, 2026). This DNA sequence acts as a sponge, as it absorbs and traps the phage (virus) that invaded the bacteria’s genome and thus acts as a vital immune defense system.
While studying the central dogma, we realize that the DRT3 gene contradicts it, but not quite reverses it. This finding was outstanding, as it was first to tell us that a protein on its own could utilize nucleic acid subunits to produce DNA, without any RNA template.
Conclusion
After analyzing the set of information provided above, it is safe to say that Crick’s “one-way flow” isn’t completely true, yet it is surely not false as still to this day, every single protein found in living things is expressed through DNA and RNA.
Exploring exceptions for the Central Dogma of Molecular Biology as the reverse transcriptase and the DRT3 protein proves to have vital importance beyond being used in basic sciences. These exceptions could be utilized in biotechnology and genetic engineering to produce certain DNA sequences, enzymes, and hormones without the long processes of transcription and translation to advance modern day medicine.
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rEFERENCES:
Predrag Šustar. (2007). Crick’s Notion of Genetic Information and the “Central Dogma” of Molecular Biology. The British Journal for the Philosophy of Science, 58(1), 13–24. http://www.jstor.org.ezproxy.aub.edu.lb/stable/4489098
Lim D, Maas WK. Reverse transcriptase in bacteria. Mol Microbiol. 1989 Aug;3(8):1141-4. doi: 10.1111/j.1365-2958.1989.tb00264.x. PMID: 2481800.
Niazi SK. Protein-directed nucleotide selection in the DRT3 defense system: mechanism, biological context, and constraints on programmability. Front Microbiol. 2026 Jun 16;17:1866040. doi: 10.3389/fmicb.2026.1866040. PMID: 42382356; PMCID: PMC13314766.