By Daniel Tarade
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The central dogma is something that all biology students learn in high school. The concept is defined as the unidirectional flow of information from DNA to RNA to protein. DNA is the hereditary blueprint for cellular and organismal functioning that encodes functional protein units, which fill structural, hormonal, enzymatic, and signalling roles. The DNA sequence, a polymer comprised of four different flavours of deoxyribonucleotides, is first transcribed into a complementary RNA molecule, a closely related stretch of ribonucleotides. During the subsequent translation, RNA is ‘read’ three nucleotides at a time. These combinations of three nucleotides, or codons, each specify a particular amino acid, which is the basic building block of the protein polymer. This process is fundamental to all life known to humanity.
In today’s age, immediately after learning about the central dogma, students are taught a compendium of supposed exceptions. RNA-based retroviruses can reverse transcribe RNA back in to DNA. Some RNA is functional and never translated into protein. The identification of gene splicing added a wrinkle. So too did the discovery of prions, those proteins that replicate and spread without any nucleic acid intermediate. But none of these processes violate the central dogma as formulated by Francis Crick in 1958[i];
Th[e central dogma] states that once 'information' has passed into protein it cannot get out again. In more detail, 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. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein…As far as I know [this dogma] has not been explicitly stated before.
Even prions do not violate the central dogma. Prions are misfolded proteins that induce other proteins to misfold. But the induction of misfolding is the not transmission of protein sequence information. Rather, the information in these proteins is separately transcribed from RNA.
Cook, N. D. (1977). The case for reverse translation. Journal of theoretical biology, 64(1), 113-135. Scientists asked if the reverse arrow from protein to RNA exists.
For some time, scientists searched for cases of reverse translation. To a few, it served as a promising hypothesis to explain genetic changes that did not lean on random mutation as a mechanism.[ii] Moss now grows over this hypothesis, long since abandoned. A testament to the once-promising idea takes the form of an April Fool’s prank on a science blog. Others laid the theoretical foundation for an equilibrium between amino acid and nucleic acid chains, which may have been important during earliest stages of life on Earth.[iii] Despite a theoretical possibility, no experimental evidence for reverse translation exists. Or perhaps it is just hiding in plain site.
During one of our departmental coffee breaks, Professor Paul Hamel strolls in and asks the students present to explain the central dogma. For reasons discussed above, we all proffered up incorrect answers. He brought our attention to Crick’s original definition and asked us if there are any exceptions. After some time, we reasoned that the central dogma remains intact to this day. Paul asked us to think about outside the box. What about the reverse translation that we do as scientists? Any university student in biology can deduce a complimentary DNA sequence from any given protein sequence. Of course. Reverse translation does exist. A simple google search will reveal multiple webservers that can take an amino acid sequence and spit out a complementary nucleotide sequence. There are a few tricks involved. There is a degeneracy when a nucleic acid sequence is translated into protein. There are sixty-four permutations of the four nucleic acids when arranged into triplet codons but only twenty amino acids. As a result, multiple codons often encode the same amino acid. For example, GAG (guanine-adenosine-guanine) and GAA both encode glutamic acid. When reverse translation occurs in silico, the most frequent codon is chosen. So here is the question — does this reverse translation violate the central dogma?
The impulse of most people is no. As quoted on at least one tutorial page, “reverse translation is not a biological process.” Although obsessed over by scientists, no one has discovered a cellular mechanism by which an amino acid sequence serves as a template to produce a corresponding nucleic acid sequence. The transfer of information from protein to DNA, however, is possible with human intervention. And humans are biological. Any denial of reverse translation requires treating human activity as technological and not natural. Hence, we need to address the divide between society and nature.
Binary thinking on nature and society bubbled to the surface during the Enlightenment. Scholars interested in studying physics, chemistry, and biology argued that these ‘natural’ phenomena are separate and external to humans and their societies and are best studied in an objective and dispassionate manner. Thus, scientists and researchers construct ‘nature’ and define with a razor’s edge the phenomena they wish to interrogate. Just because this distinction simplifies the research process does not mean it is apolitical. It is ideological.
The classic example used to illustrate the arbitrary divide between nature and technology is the beaver dam. A beaver dam is a sophisticated construction that provides shelter and modifies the local hydrology. If beavers did not exist, would we claim that dams do not exist in the natural world despite our own constructions? Many other examples highlight the absurd distinction between technology and nature. What is the difference between a chimp using a rock to smash a nut and a human using a nutcracker? Or a spider using a web to snatch flies and a human using a net to catch fish? I contend that the difference is one of degree but not of kind. More and more, scholarship aims to entrench the human experience the natural world.[iv] The rapid emergence of extinction rebellion, a group demanding the halting of biodiversity loss and continued greenhouse gas emissions, exemplifies popular support for dismantling the society/nature divide. The era of human exceptionalism is coming to an end, whether you like it or not.
Humans are biological. Everything humans do is biological. As athletic competitions are illustrative of human biology so to is human engineering and scientific inquiry. We pioneered reverse translation and broke the central dogma. If you still cannot wrap your head around that, imagine yourself an alien visitor to the planet Earth. Would you differentiate humans from other fauna? No. You would identify humans as apex predators or keystone species, but your study of humans might be reminiscent of how humans study chimps or other ‘higher’ organisms. As an alien Jane Goodall, you might even astonish members of your scientific institution with evidence of biological reverse translation.
[i] Crick, Francis HC. (1958). On protein synthesis. Symp Soc Exp Biol. 12,138-63.
[ii] Cook, N. D. (1977). The case for reverse translation. Journal of theoretical biology, 64(1), 113-135.
[iii] Nashimoto, M. (2001). The RNA/protein symmetry hypothesis: experimental support for reverse translation of primitive proteins. Journal of theoretical biology, 209(2), 181-187.
[iv] Goldman, M., & A. Schurman, R. (2000). Closing the “great divide”: New social theory on society and nature. Annual review of sociology, 26(1), 563-584.