The Central Dogma has had an enormous impact on the way genetics research has developed over the past 50 years. Basically, the dogma states that DNA genes encode mRNA, and mRNA allows proteins to be constructed, and proteins do all the work needed for cells to function. There is a linear logic here that fits into a view of the genome that is static throughout its life and provides a blueprint for life. This is how Franklin and Vondriska introduce their paper:
"Arguably the greatest postmodern coup for reductionism in biology was the articulation of the central dogma. 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."
The classic view of the central dogma of biology (source here)
In their review of these issues, Franklin and Vondriska present a systems biology perspective which makes it clear that the central dogma is deficient in numerous ways and that our understanding of living things needs extensive revision. This is an imperative drawn from scientific research and should not be regarded as just another 'point of view'.
"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 individual; that changes occurring in somatic cells cannot be inherited (also known as Lamarckian evolution); 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."
Undoubtedly, the trigger for change has been the discovery of extraordinary complexity in cellular processes as revealed by systems biology research. It is now necessary to refer to networks of interactions when explaining any aspect of cellular function. And the very existence of these networks defies the central dogma:
"However, these studies have yet to reveal an invariant relationship between structure and function. There is no code that can account for how the hierarchical structure of DNA and proteins establishes the complex genomic regulatory programs that exist in distinct differentiated cells, as there is to explain, for example, how DNA encodes RNA and RNA, protein."
Systems biology has stimulated thought about the complexity of interacting entities and processes. There is an enormous difference between a DNA gene coding for a protein, and the formation and orchestration of the infrastructure of the whole cell. Those who grasp the nettle by posing questions about cellular processes realise that we do not have the answers. Some form of organising principle must be invoked - transcending the genetic code for making proteins. The central dogma is not central enough - for the really important questions are never asked by its advocates!
"The presence of such properties suggests emergent control in the formation of the network in addition to emergent control of its function once formed. How can this emergence be measured rather than just observed? An enigma in biology is how a cell with (at least) thousands of proteins can reproducibly form and behave in the same manner without central control."
Research findings that point to the inadequacies of the central dogma are summarised in a Table and discussed in the text. It is not the purpose of this blog to precis this part of the paper, but the key issues for consideration are evident in these words by the authors:
"[W]e identify 5 ways in which "-omics" technologies are changing basic and clinical research and contributing to a revisiting of the central dogma: First, by deemphasizing the unidirectional flow of information (i.e, DNA to RNA to protein); second, by placing an emphasis on modules of genes/proteins/molecules rather than individual factors; third, by enabling the discovery and quantification of emergent properties present at different scales of information; fourth, by revealing the role of networks in biological function; and fifth, by allowing for new dimensionality in the analysis of all biological molecules."
The key point being made here is that a change in thinking about molecular biology is urgently needed. There is a tendency for people to say that the central dogma is still valid, but it needs supplementing and enhancing. This would be a mistake. The consequence of treating this as incremental learning is that fundamental questions are neglected and science suffers. Arguably, science is already suffering. The meagre results emerging from medical genetics appears to be a consequence of researchers adopting the central dogma paradigm; and there are serious concerns about the whole of GM food research because the science shows no signs of being informed by any systems thinking. Incremental learning and tweaking of the central dogma can be ruled out because the five observations discussed in the review paper demonstrate outcomes that are not predicted by the central dogma, and in some cases actually falsify the central dogma.
This conclusion has important implications for the debate about design in nature. What can be said about the organising principles within the cell? Should intelligence be invoked, or is causation naturalistic? The authors refer to an "unknown process" - which at very least implies that there is a scientific debate to be had. However, note this concluding paragraph of the paper:
"The greatest present challenge for biology is the limit of reductionism. The term systems biology itself underscores our linguistic circumscription of this problem. A system, no matter how complex, is a defined entity; it is a human creation. We conceptualize an evolvable central information unit that describes (and orchestrates) the piecewise assembly of the machine that is a cell. We conceptualize watches, even if we shun the watchmaker."
The authors are saying that by using a systems biology approach, we need to invoke the concept of a central information unit that orchestrates cellular processes. In other words, the cell looks designed and there are analogies with human creations. But they also suggest that we may choose to shun the designer. Some of us want to see the day when shunning the designer of cells is perceived to be as incoherent and as irrational as shunning the designer of a watch.
Genomes, Proteomes, and the Central Dogma
Sarah Franklin and Thomas M. Vondriska
Circulation: Cardiovascular Genetics, October 2011; 4: 576 | DOI: 10.1161/CIRCGENETICS.110.957795
Abstract: Systems biology, with its associated technologies of proteomics, genomics, and metabolomics, is driving the evolution of our understanding of cardiovascular physiology. Rather than studying individual molecules or even single reactions, a systems approach allows integration of orthogonal data sets from distinct tiers of biological data, including gene, RNA, protein, metabolite, and other component networks. Together these networks give rise to emergent properties of cellular function, and it is their reprogramming that causes disease. We present 5 observations regarding how systems biology is guiding a revisiting of the central dogma: (1) It deemphasizes the unidirectional flow of information from genes to proteins; (2) it reveals the role of modules of molecules as opposed to individual proteins acting in isolation; (3) it enables discovery of novel emergent properties; (4) it demonstrates the importance of networks in biology; and (5) it adds new dimensionality to the study of biological systems.
Tyler, D. Beyond Genes and the Central Dogma, ARN Literature Blog (14 September 2007).
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