It's frustrating to read yet another scientific paper announcing the demise of the Central Dogma of Molecular Biology. If you've been following the literature, you'll know that the Central Dogma is regularly killed off about ten times per year—a rate that's been fairly constant for thirty years. But to paraphrase Mark Twain, reports of the death of the Central Dogma are greatly exaggerated.
Let's look at the paper by Sarah Franklin and Thomas M. Vondriska from the David Geffen School of Medicine in Los Angeles California (USA) (Franklin and Vondriska 2011). This is a paper that specifically addresses the Central Dogma of Molecular Biology so you'd expect that the authors understand what they are attacking, right?
Here's the opening paragraphs ...
Arguably the greatest postmodern coup for reductionism in biology was the articulation of the central dogma.1 Not since “humors” were discarded from medical practice and logic and experiment instituted as the cornerstones of physiology (which they remain today) had such a revolutionary idea transformed biology and enabled scientific inquiry. Because of its simplicity, the central dogma has the tantalizing allure of deduction: If one accepts the premises (that DNA encodes mRNA, and mRNA, protein), it seems one cannot deny the conclusions (that genes are the blueprint for life). As a result, the central dogma has guided research into causes of disease and phenotype, as well as constituted the basis for the tools used in the laboratory to interrogate these causes for the past half century.Reference 1—the reference to the meaning of the Central Dogma—is the Nature paper published by Francis Crick in 1970. That paper was intended to clarify the meaning of the Central Dogma after the discovery of reverses transcriptase. Crick was concerned about the fact that many scientists were confused about the meaning of the Central Dogma so he attempted to set them straight by clearly stating that the Central Dogma was NOT "DNA makes RNA makes protein" (the Sequence Hypothesis) but ....
The past decade, however, has witnessed a rapid accumulation of evidence that challenges the linear logic of the central dogma. Four previously unassailable beliefs about the genome—that it is static throughout the life of the organism; that it is invariant between cell type and individual2–4; that changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution5); and that necessary and sufficient information for cellular function is contained in the gene sequence—have all been called into question in the last few years. Revelations of similar scale have occurred in the transcriptome, with the discovery of the ubiquity (and variety) of mRNA splicing.6 So too with the proteome, which has undergone perhaps the most dramatic shift in understanding as a result of the aforementioned changes to the transcriptome and the genome, as well as by the explosion of technology development that has enabled both quantitative and qualitative analysis of large groups of proteins and their modifications in a single experiment. It is now clear that information flows multidirectionally between different tiers of biological information, of which genes, transcripts, and proteins constitute only the most obvious 3.
... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)I explained this in Basic Concepts: The Central Dogma of Molecular Biology.
The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
Since Sarah Franklin and Thomas M. Vondriska reference the 1970 Crick paper, you'd expect them to have read it but they clearly haven't read it at all or they would know that their definition of the Central Dogma is wrong. I don't understand how this happens. How is it possible that two scientists could publish a paper criticizing the Central Dogma without even knowing what the Central Dogma actually says? How is it possible that the reviewers and editors of this journal could let such a paper be published?
For that matter, how is it possible to publish yet another paper announcing the death of the false version of the Central Dogma? How many times can you beat a dead horse even if it's a mythical horse?
Footnote: Let's look at the "Four previously unassailable beliefs about the genome."
- (the genome) is static throughout the life of the organism. We've known that this is untrue since the 1970s when genome rearrangements in bacteria were discovered. We've known about immunoglobulin gene rearrangements for over twenty-five years. We've known about mating type in yeast for at least as long as that. We've known about drastic genome rearrangements in protozoa since the 1980s. I assume that what Franklin and Vondriska really mean to say is they have just discovered what they should have learned as undergraduates.
- (the genome) is invariant between cell type and individual. See above. Read a textbook.
- changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution. I'm not sure what this means. Do they mean that changes occurring in somatic cells can somehow be transferred to the germ line and inherited by offspring?
- necessary and sufficient information for cellular function is contained in the gene sequence. A basic principle of biology is that you need a cell to make another cell. Most people learn this in high school.
Crick, F.H.C. (1958) On protein synthesis. Symp. Soc. Exp. Biol. XII:138-163.
Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227, 561-563. [PDF file]
Franklin S. and Vondriska, T.M. (2011) Genomes, Proteomes, and the Central Dogma. Circulation: Cardiovascular Genetics 4:576 [doi: 10.1161/CIRCGENETICS.110.957795]