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Epigenetic inheritance

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Structure of DNA chromosomes showing histone protein.

Epigenetics is the study of heritable changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence, hence the name epi- (Greek: επί- over, above) -genetics. These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations. However, there is no change in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.

In recent years, it has become increasingly clear that cellular inheritance is not limited to simple Mendelian genetics. The term epigenetics has been used to describe these types of inheritance that are not due to changes in the DNA nucleotide sequence, yet result in a new trait being passed from parent to offspring. Fixed DNA sequences wrapped around Histone proteins gives shape to the physical structure of the genome by coiling tightly inactive genes making them unreadable or inaccessible, while uncoiling active genes making them freely accessible. Maintenance of structure of the genome and strategic points of chemical locations upon DNA sequences are controlled by the epigenome and enable the genome to produce phenotype expression. Epigenetic chemical tags react to natural environmental stimuli and manifest through diet or stress for example.[1]

Epigenetics is an incredible field of study that encompasses a whole array of cellular processes. Some epigenetic mechanisms include: DNA methylation, histone modifications of DNA, genomic imprinting, noncoding RNAs, and X-chromosome inactivation. These result in changes in organisms or cell types, including cellular differentiation. Basically, epigenetics is a blanket term used to describe any type of cell memory passed on to offspring that does not involve direct manipulation of the DNA sequence.

The discovery of this process has serious implications for creation biology, given the fact that major phenotypic changes can occur without the Darwinian process of genetic mutation and natural selection.[2]

Contents

Background

Insight into epigenetics began with scientific observations that could not be accounted for with knowledge of basic genetics and Mendelian inheritance. One of the simplest observations has been noticed through studies of identical twins. Even though they have the exact same DNA sequence, they often possess a number of physical differences, including different susceptibilities to disease and different facial features.[3] Because of this importance of epigenetic mechanisms in the actual appearance of an organism, some scientists have called epigenetics the genetic puppeteer controlling the gene “puppets”.[4]

Epigenetic control of the genetic code is not something to be taken lightly. Allowing another unit (in this case epigenetics) to have a place in inheritance goes against long-held genetic beliefs. The groundbreaking scientist, Francis Crick, proposed a theory called the central dogma, which delineates the transfer of genetic information. He stated that transfer of genetic information can never occur from protein to protein or from protein to DNA or from protein to RNA. It always flows from DNA to RNA to protein.[5] However, the findings of epigenetics seem to refute some of these ideas. From study, it seems that the behavior of genes in offspring can be dependent on the life experiences of the parent.[6]

Since the sequencing of the human genome, more and more objections to Crick’s central dogma have arisen. Scientists have found that the sequencing of the entire genome has not answered every genetic question and that more and more mysteries abound.[7] Epigenetics might provide some of the answers.

Eva Jablonka and Marion J. Lamb co-authored a seminal work about the traditional notions of Darwinian evolution, encapsulating the current debate while progressing an expanded view that incorporates four units of variation inheritance in biological evolution. Their popular level book was released in 2005 called, Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life.[8] The book presents the case for a new type of understanding regarding variation inheritance and challenges long-held notions of the scientific establishment.

Mechanisms

Two of the best-studied mechanisms of epigenetic inheritance are DNA methylation and histone modification of DNA. These involve the modification of DNA itself (DNA methylation) or the modification of the proteins that associate with DNA (histone modification). A more general epigenetic mechanism, which is no less important, is cell differentiation. Finally, a newly discovered mechanism is the contribution of noncoding RNAs. All of these epigenetic mechanisms are interconnected in various ways and may work together to form the final product of inherited information.

DNA methylation

The Methyl substitution group.

Methylation of DNA involves the addition of methyl groups (-CH3) to DNA nucleotides. DNA methylation impacts genetic control by the repression of gene expression.[9] Genes that are methylated are “turned off.” Studies have shown that DNA methylation plays an important role in several known epigenetic mechanisms, including genomic imprinting. Not only are DNA methylation patterns a type of cell memory system but it is also part of the system that regulates transcription.

Histone modification and chromatin structure of DNA

Cells can inherit histone modification and chromatin structure. In essence, these modifications to the packaging of DNA tend to make DNA more or less accessible and therefore more or less useable in the cell.[10] Histone variants and histone modifications provide an important level of epigenetic inheritance in the cell.[11] One important example of chromatin structure affecting epigenetic inheritance in the cell is X-chromosome inactivation.

Cell differentiation

An important part of multicellular organism survival is cell differentiation. When an embryo first develops, the cells begin to differentiate into the new structures they will soon form. In an adult, those cells retain the memory of their cell type. For example, liver cells produce more liver cells. This ability to remember can be caused by both of the above mechanisms—DNA methylation and the histone code, as well as positive feedback loops that are activated in the cell itself. These positive feedback loops may be as simple as a gene being turned on, which, in turn, transcribes its own activator.[12] Other factors may well have an impact as seen by genomic reprogramming.

Noncoding RNAs

Small noncoding RNAs are also termed microRNAs and new studies have shown their epigenetic role. Non-coding RNAs are RNA molecules that are transcribed from DNA in the nucleus, but are not translated into protein in the cytoplasm of the cell. They are implicated with silencing chromatin, degradation of messenger RNA and blocking translation of certain genes. They may also have a role in cancer, like many of the other epigenetic mechanisms mentioned.[13] Larger non-coding RNAs seem to play an important role in genome regulation as well, by participating in the chromosomal structure of heterochromatin, silencing transposable elements and eliminating DNA. All of these mechanisms have not been shown in humans, but are present in other organisms. [14]

Impact

Given the incredible mechanisms of epigenetic influence on inheritance and the cell, it is not surprising that scientists are finding more and more uses for epigenetic information. It has been implicated in cancer and genomic reprogramming, and has provided important roles for what was once considered junk DNA.

Cancer

DNA in cancer cells has an unusually high level of DNA methylation. This suggests that important genes have been switched off. Also, de-methylation (removal of methyl groups) may have the ability to switch on cancer genes.[4] Interestingly enough, the high level of DNA methylation seems to be found at CG islands, so this methylation event represses transcription of the genes normally associated with CG islands. Because of its prevalence in cancer cells, DNA methylation may have use as an early detection screen for cancer when it is found on certain genes.[9]

All of the epigenetic changes mentioned previously have been shown to contribute to genome instability, activation of oncogenes (cancer-causing genes), silencing of tumor suppressor genes and inactivation of DNA repair systems. However, epigenetic causes of cancer bring hope to cancer therapy, because many of them are reversible, so new treatments are now beginning to be studied.[15]

Genome reprogramming

Early development of cells and organisms involves changes in DNA methylation, as well as conservation of certain types of DNA methylation, providing evidence for the role of epigenetics in genome programming as well as genome reprogramming. The actual DNA sequence, or genome, is programmed during development to express certain genes at appropriate times. This programming is accomplished through epigenetic influences on the genome.[13]

Heterochromatin

Approximately 50% of the human genome is composed of transposable elements and other repetitive DNA sequences.[16] Once felt to be superfluous, this former junk DNA has been found to have important functions.[17] One of these is a role in epigenetic control of the cell. Repetitive DNA is highly methylated, has histone modifications, is found in heterochromatin and its modifications tend to depend on the state of a cell’s differentiation.[16] So, whether it actually has a role in epigenetics or epigenetic mechanisms help control this repetitive DNA, the two are functionally intertwined.

Research

Recent

As in all scientific endeavors, new information is gained daily in regards to epigenetics. There has been an incredible amount of research done on epigenetics in the last 10 years, and more will surely follow. Some of this research has turned up interesting data.

Several different studies have shown the possibility of trans-generational epigenetic inheritance among humans and animals. These studies have shown links between grandfather’s food supply and grandson’s mortality index and paternal smoking and obesity in sons.[18] Other studies have shown the importance of maternal nutrition not only in the health of her children, but her grandchildren as well.[19]

Additionally, studies in rats have shown that increased maternal care results in positive changes in an adult rat’s gene expression and stress levels, independent of the actual DNA sequence possessed. This is especially fruitful as it is not the result of mutation. The epigenetic programming of these rats showed higher levels of DNA methylation and histone acetylation at regulatory regions of the genes in question.[20]

It is important to note that research into epigenetics is a complicated process. The human genome project’s mapping of the human genome was an incredible undertaking, but it involved DNA that stays the same from cell to cell. In contrast, each of the approximately 200 types of cells of the human body has its own epigenetic mechanisms. And even these may change during development, in processes like cancer, or when an organism ages.[21] So research will continue into epigenetics, but it may be a slow and difficult process at times.

Future research

The implications of epigenetic research are many. With the connection to cancer and changes in the early life of humans, epigenetics may impact all parts of human physiology and pathology. It may provide insight into certain human behaviors as well as providing a therapeutic route of treatment.[13] Since epigenetics is a combination of many types of cellular control, it is not easily defined and as more research continues, it has become clear that all of these mechanisms may be intertwined and working together.

Although epigenetic researchers first began by focusing on one area of study (like DNA methylation), recently these same researchers have been looking at epigenetics as a whole and the field of epigenetics is blossoming.[22] Additionally, as epigenetics has impacted scientific research, geneticists have had to allow for the presence of additional information in the cell apart from the DNA sequence. Now it seems that the epigenome provides a place for the environment to directly impact the expression of genes. This new chain of interaction from the environment to the epigenome to gene expression, and thus phenotypic expression produces what is called an epigenetic landscape for scientists to traverse.

New ideas arise all the time, including one that claims the cell is fundamentally epigenetic rather than genetic, an idea that goes along with the cell providing stasis for the organism.[23] New data will be forthcoming as well, as researchers gain funding for epigenetic mapping, which will focus on DNA methylation and histone modification of DNA. With more and more research being done everyday, this list will only continue to grow and will probably change with each new development.

Implications to creation science

Epigenetics sheds more and more light on how God made this world and the brilliance of His design. It provides some expected evidence into the function of so-called junk DNA. It also is important to creationists because it provides a potential mechanism for the stability of the created kinds (epigenetic inheritance) without reducing the potential for variation among species (DNA inheritance). Epigenetic inheritance increases the known complexity of the cell immeasurably, thus providing more evidence for design and fodder for creationists in the evolutionary debate.

Epigenetics is another layer of complexity that makes up life. It is also considered a potential mechanism for the stability of the created kinds (epigenetic inheritance) hypothesis without reducing the ability for vast diversity among species (DNA inheritance). Epigenetic inheritance being the phenotype traits expressed through chemical reaction during development coupled with environmental triggers, while DNA inheritance are the phenotype traits expressed exclusively by a chance mutation in the DNA nucleotide sequence. Original representative kinds of life were intelligently designed with separate epigenetic makeups that allowed diversification in nature when coupled with genetic variation of mutation. Therefore producing wide-ranging diversity of biology on Earth through a polyphyletic origin of life, or more than one kind of original life (more than one epigenetic-genetic axis of diversity) that can also be called pattern pluralism.[24] Furthermore classic Darwinian natural selection and evolution ontogeny of traits can be found within epigenetic and genetic collaboration, it is not merely isolated genes that is the unit of heredity as neo-Darwinism has posited for the past 50 years. It is much more complex, consisting of networks of interactivity with epigenetics emerging as the mechanism interfacing with genetic systems. Even during speciation epigenetics is at work, allowing in time perhaps, experimental observation of transition change, or what is called macro-evolution by Eva Jablonka, a leading theorist and geneticist.[25]

References

  1. Epigenetics -Environmental factors can alter the way our genes are expressed, making even identical twins different. Aired July 24, 2007 on PBS
  2. Evolution in Four Dimensions Presentation by Eva Jablonka, Tel Aviv University. published: Oct. 23, 2009, recorded: September 2009
  3. Fraga, Mario F., Esteban Ballestar, Maria F. Paz, Santiago Ropero, et al. Santiago, et al. “Epigenetic differences arise during the lifetime of monozygotic twins.” PNAS 102 (2005): 10604-10609. Mar 5 2010. (p 10604)
  4. 4.0 4.1 White, David. The genetic puppeteer. Technical Journal 30 (2008): 42-44. Feb 20 2010. (p 42)
  5. Crick, Francis. “Central dogma of molecular biology.” Nature 227 (1970): 561-563. Web. Feb 27 2010. (p 561)
  6. What genes remember by Philip Hunter. Prospect Magazine Issue 146, May 24, 2008.
  7. A dissenting voice as the genome is sifted to fight disease by Nicholas Wade. New York Times, September 15, 2008
  8. Eva Jablonka and Marion J. Lamb, Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life (MIT Press 2006)[1]
  9. 9.0 9.1 Research interests by Keith D. Robertson. University of Florida.
  10. Misteli, Tom. “Beyond the sequence: Cellular organization of genome function.” Cell 128 (2007): 787-800. Web. Mar 8 2010. (p 790)
  11. Shi, Yang. “Taking Epigenetics Center Stage.” Cell 128 (2007): 639-640. Mar 5 2010. (p 640)
  12. Epigenetic inheritance By Fact Index, Author unknown. Accessed March 15, 2011.
  13. 13.0 13.1 13.2 Szyf, Moshe. The epigenetic impact of early life adversity. Canada: McGill University, 2009. Feb 27 2010. (p 29)
  14. Zaratiegu, 773
  15. Szyf, 30
  16. 16.0 16.1 Bernstein, Bradley E., Alexander Meissner, and Eric S. Lander. “The mammalian epigenome” Cell 128 (2007): 669-681. Mar 8 2010. (p 676)
  17. Walkup, Linda K. “Junk DNA: evolutionary discards or God’s tools?” Technical Journal 14 (2000): 18-30. Feb 20 2010. (p 21)
  18. Whitelaw, Emma. “Sins of the fathers, and their fathers.” European Journal of Human Genetics 14 (2006): 131-132. Feb 27 2010. (p 131)
  19. White, 43
  20. Szyf, 31
  21. Baker, Monya. “Epigenome: mapping in motion.” Nature Methods 7 (2010): 181-186. Web. Mar 20 2010. (p 181)
  22. Baker, 185
  23. The Organic Codes by Marcello Barbieri. Biologiateorica.
  24. Pattern pluralism and the Tree of Life hypothesis January 29, 2007, doi: 10.1073/pnas.0610699104 PNAS February 13, 2007 vol. 104 no. 7 2043-2049
  25. Evolution in Four Dimensions Presentation by Eva Jablonka, Tel Aviv University. published: Oct. 23, 2009, recorded: September 2009

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