Epigenetics

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The term ‘epigenetics’ was coined in 1947 by Conrad Hall Waddington, a British embryologist and geneticist. He defined this scientific field as “…the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being…”[1] Epigenetics has also been described as “the study of those processes by which genetic information ultimately results in distinctive physical and behavioral characteristics.”[2] The ability of epigenetics to affect the phenotype of offspring has prompted the term epigenetics to be synonymous with the phrase “epigenetic inheritance.” So stated simply, epigenetics is a marriage of developmental biology and genetics.

A prime example of epigenetics in action is an experiment performed on agouti mice by researchers Randy Jirtle and Robert Waterland. Agouti mice, which are genetically predisposed to obesity, cancer, and other unhealthy conditions, were given foods rich in methyl donors before conception and during gestation. Methyl donors are chemicals that can attach to a gene and “turn it off.” Without any invasive changes or genetic engineering to a single base pair, the degenerative condition was eliminated from many of the mother’s progeny. The methyl donors attached to the deleterious genes in the genome of the mice embryos and suppressed their expression.[3]

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Epigenome

The epigenome is the status of the total suite of mechanisms and features that express the genotype. The process of cataloging this set of features has begun.[4] There are now two groups that have initiated Human Epigenome Projects; the first in Europe and the second in the United States. The project in Europe was initiated in 2003 by the Wellcome Trust Sanger Institute, Epigenomics AG, and the Centre National de Génotypage. The project in the United States was proposed in December 2005 by a group of 40 international scientists, and released one of their first papers in the October 2006 edition of Nature Genetics.[5]

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Mechanisms

The field of epigenetics studies processes and mechanisms that direct phenotype by superimposing information on the genome, or otherwise controlling the genome. Currently known mechanisms can affect phenotype by controls on base pairs, histones, or chromatin, not by changes in the base pair sequence. As currently understood, the distinguishing feature of epigenetic processes is that they modulate gene expression without changing the sequence of base pairs in the genetic code. Because of the non-genetic action of known epigenetic mechanisms, the term ‘cell memory’ has been used to describe these processes. Below are some of the epigenetic processes. Surely as research continues, more mechanisms will be discovered.

  • Transdetermination is a process wherein during the development of cell types from progenitor cells, a cell type that has differentiated into one cell type changes into a different cell type. For example, cells differentiated to make a leg switch to a cell type that forms a wing.[6] Ernst Hadorn pioneered research into this mechanism, and virtually no researchers are currently publishing research on this mechanism.[7]
  • DNA methylation, also known as “gene silencing” or “chromosome silencing,” is by far the most studied mechanism. This process is typified by the deactivation of cytosine in DNA through methylation caused by “maintenance methylase.” Maintenance methylase is proposed as the cause of the “switching on and off” of particular genes.[8]
  • Regulatory RNA is a host of ribonucleic acids that direct cellular process in the expression of the genome and epigenome, especially producing isoforms of a protein.[9]
  • “Histone code” or the “nucleosome code” is formed by the mechanism that packages the DNA into chromatin. Some base pairs may remain packed during the entirety of interphase, making those sequences unavailable to the replicating machinery in the nucleus.[10]
  • Epimutations are specific changes in the epigenome, characterized by heritable changes not due to changes in DNA sequence.[11]
  • Epigenotype is the actual expression of a specified developmental cell type.[12]
  • Developmental clocks are lesser-known mechanisms of unfolding the genetic program for development. This would be a mechanism that counts a specific number of cell divisions before a given gene or genes are activated or inactivated.
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Research identifying epigenetic mechanisms and triggers

  • Nursing and methylation [1], [2]
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Medicine and epigenetics

It has been found that epigenetic mechanisms are crucial for developmental processes, so epigenetics has many applications in the field of medicine. Epigenetic disorders have been linked to disease and developmental problems.[13] Some cancers, developmental disorders, metabolic blocks and many other illnesses are caused by epigenetic factors. “Through numerous studies, Szyf has found that common signaling pathways known to lead to cancerous tumors also activate the DNA-methylation machinery; knocking out one of the enzymes in that pathway prevent the tumors from developing. When genes that typically act to suppress tumors are methylated, the tumors metastasize. Likewise, when genes that typically promote tumor growth are demethylated – that is, the dimmer switches that are normally present are removed – those genes kick into action and cause tumors to grow.”[14]

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Implications of epigenetics

Epigenetics has profound implications for biology, especially the current gene-centric view of the living world. These implications will affect genetics, heredity, identity, developmental biology, evolutionary biology, and medicine in many ways. “…We have to change basic concepts of heredity and of evolution.”[15] In time, this change will also come to science education.

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Genetics, postgenetics and epigenetics

“Until recently, the idea that your environment might change your heredity without changing a gene sequence was scientific heresy. . . . That turns out not to be the case.”[16] Epigenetics asks many questions of those researching the role of the genetic code.

Because of the challenge epigenetics poses to the gene-centric view of biology, epigenetics is seen as a revolutionary field for biology. The implications of epigenetics and other non-gene-based biological factors are leading many biologists to a “postgenetic” view of the living world. According to the website of the International Postgenetics Society, ‘postgenetics’ is a synthesized response to “the conceptual meltdown of ‘gene thesis’ and ‘JunkDNA antithesis.’ Instead of a straight-forward set of four base pairs, postgenetically there are certainly five base pairs, and possibly more.[17]

Many researchers are strongly resisting the changes proposed by epigenetics research. Pharmacologist Moshe Szyf has been subjected to intellectual abuse by his fellow scientists, having a paper dismissed by a peer reviewer as a “misguided attempt at scientific humor.” On another occasion Szyf was frankly told that, “Let me be clear: Cancer is genetic in origin, not epigenetic.”[18]

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Evolutionary biology and Lamarckianism

Despite the obvious importance of evolution in the history of life, and the emerging importance of a long history of epigenetics (since 1947), the evolutionary implications of epigenetics are almost completely unexplored. Evolutionary theory has played a critical role in biology for almost 150 years, and epigenetics research has been ongoing for almost 70 years. Despite the historical overlap, the implications of epigenetics on evolution are mostly unexplored and conclusions are often contradictory. This is principally due to the gene-centric nature of neo-Darwinism. The heritability of epigenetic traits has revived the evolutionary concepts of French naturalist Jean-Baptiste Lamarck, which often rival the evolutionary concepts of neo-Darwinism.[19] Since diet or other contingent behaviors can affect the expression of the genotype and the resulting phenotype, Jirtle states bluntly, “Epigenetics introduces the concept of free will into our idea of genetics.”[20]

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Science education and epigenetics

The implications of epigenetics are also particularly acute in science education. Some major scientific reference resources consulted in preparation for writing this paper did not have a single entry covering epigenetics. Phenotype is typically taught as being the direct result of genotype. This absence, however, makes biology education inadequate for a fuller understanding of biological processes, since some of the general rules of genetics are already shown to be inaccurate in a multitude of cases, with more irregular examples published in the peer review literature on a regular basis. The relatively new field of epigenetics poses many questions to current biological science, especially to geneticists and evolutionary biologists.

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Epigenetics, evolution, and intelligent design

What does epigenetics mean for intelligent design? If biological organisms were designed, it is likely that there will be epigenetic mechanisms that exhibit Specified Complexity and Irreducible Complexity. Additionally, the way in which epigenetics has been eschewed by those of neo-Darwinian views will be shown as another historical failure of the gene-centrism of neo-Darwinian views. This is because neo-Darwinism has mislead our research focus disordinately on the coding genes, often leading scientists to seek answers where none were to be found (see the example of Szyf's research above). The design perspective would have been looking for human-technological characteristics of context-dependency, information hierarchies, and epigenetic mechanisms, especially once the informational and teleological nature of biology was revealed by molecular biology and biochemistry. (For other examples of this, see Junk DNA and Coding analogies.)

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Critical thinking and further study

  • Do epigenetic mechanisms have any genetic basis?
  • Are there any mechanisms of the epigenotype that are communicated from parent to progenitor intact, with no genetic involvement?
  • What does epigenetics say about heritability of phenotype?
  • Does the emerging field of epigenetics mean that there may be permanently heritable traits that are independent of the genome?
  • Does non-coding DNA (or Junk DNA) play a role in epigenetic factors?
  • What is the dynamic between evolutionary mechanisms and epigenetic mechanisms?
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See also...

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References and notes

  1. ↑ Waddington CH (1975) The Evolution of an Evolutionist. Edinburgh, Reprint, p. 218
  2. ↑ Parker S, ed. (1989) “Epigenetics.” Dictionary of Scientific and Technical Terms, 4th ed. New York (NY): McGraw-Hill, p. 652
  3. ↑ Watters E (2006) “DNA Is Not Destiny.” DISCOVER, 27:11, November 2006, p. 33
  4. ↑ Garber K (2006) “U.S. Human Epigenome Project.” Environmental Health Perspectives, 114:3; p. A 165-6
  5. ↑ Eckhardt, et al (2006) “DNA methylation profiling of human chromosomes 6, 20 and 22.” Nature Genetics: published online, 29 October 2006.
  6. ↑ Ursprung H, Nothiger R (1972) “Biology of Imaginal Discs.” Berlin: Springer Verlag.
  7. ↑ Holliday R (2006) “Epigenetics: a historical overview.” Epigenetics, 1:2, 76-80; March/April 2006, p. 77
  8. ↑ Holliday 2006, p. 77
  9. ↑ Holliday 2006, p. 79
  10. ↑ Watters 2006, p. 34
  11. ↑ Holliday 2006, p. 78
  12. ↑ Holliday 2006, p. 79
  13. ↑ Archer T and Wade P (2006) “Epigenetics:Environmental Instructions for the Genome.” Environmental Health Perspectives, 114:3, March 2006.
  14. ↑ Watters, 2006, pp. 34-35
  15. ↑ Watters, 2006
  16. ↑ Watters, 2006, p. 34
  17. ↑ Holliday 2006, p. 79
  18. ↑ Watters 2006, p. 34
  19. ↑ Jablonka E; Lachmann M and Lamb M (1992) “Evidence, mechanisms and models for the inheritance of acquired characteristics.” Journal of Theoretical Biology. 158: 245-268.
  20. ↑ Watters 2006, p. 34
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Additional references

  • Waterland RA, Jirtle RL (2003) “Transposable elements: targets for early nutritional effects on epigenetic gene regulation.” Molecular and Cellular Biology, 2003 Aug;23(15):5293-300.
  • Berger SL (Ed.), Nakanishi O (Ed.), Haendler B (Ed.) (2006) The Histone Code and Beyond: New Approaches to Cancer Therapy. Ernst Schering Research Foundation Workshop, ISBN 3540278575.
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External links

Retrieved from "http://www.researchintelligentdesign.org/wiki/Epigenetics"
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