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It is a common topic over the years on which number of studies have been conducted to reveal the effects of epigenetics and to focus on its development among organisms. It was an interesting topic because it was one way of understanding genetics and its main aspects. Epigenetics also helped researchers in topics like stem cell research, preventing aging process, cloning opportunities, agriculture, synthetic biology, conservation of species, and most of all evolution. Environment is one of the factors which has a huge effect on epigenetic changes.
Epigenetic is the study of hereditary changes in phenotype due to mechanisms other than changes in the underlying DNA sequence occurs in cell division. It is a non genetic factors are the cause of organsims's genes to express differently ( epigenetics pg. 28). According to Brona McVittie the idea of epigenetic became popular in 1942 by Corad Waddignton but epigenetic actually appears in the literature as far back as the mid 19th century back to Aristotle; he believed in epigenesis as the development of individual organic form from the unformed. But as the time changed, the meaning of epigenetic changed as well. However, implementation of those changes is likely to be spontaneous and is considered either as response to environment factors or in response to particular allele. Brona also stated that changes may remain through cell divisions for the remainder of the cell's life or for multiple generations.
Everyone have different opinions about epigenetics, according to one of the editorial " modern science defines epigenetics as meiotically and mitotically stable alteration in gene expression that are not based on DNA sequence changes and involve process that impact chromatin structureâ€¦..and genomic imprinting ( 2008, wiley Liss.)"Now some people confuse epigenetics with genetics but "The difference between genetics and epigenetics can probably be compared to the difference between writing and reading a book. Once a book is written, the text (the genes or DNA: stored information) will be the same in all the copies distributed to the interested audience. However, each individual reader of a given book may interpret the story slightly differently, with varying emotions and projections as they continue to unfold the chapters. In a very similar manner, epigenetics would allow different interpretations of a fixed template and result in different read-outs, dependent upon the variable conditions under which this template is interrogated (Epigenetics pg. 28.)"
Scientists have been studying about the molecular foundation of epigenetic. Molecular basis of epigenetic is really complex, one of the molecular foundation of epigenetic involves the modification of the activation of certain genes, but not the basic structure of DNA. According to an article Epigenetics by MeD India, "The molecular basis of epigenetics is a complex phenomenon and involves changes in theÂ switching 'on' and 'off'Â of certainÂ genes.Â Even theÂ proteinsÂ associated with the DNA may be switched on or may be silenced. The phenomena of epigenetics explain why only relevant genes are selectively expressed in differentiated cells of a multi-cellularÂ organismÂ while the others remain silent." This article also stated that most of the epigenetic changes in an organism occurs during mitosis, while cell is dividing and are apparent only during while an individual is alive. And these changes only get inherited by the next generation only if a mutation occurs in DNA.
According to MeD India, specific processes of epigenetic include bookmarking, which is known to function as an epigenetic mechanism for passing on cellular memory of the pattern of gene expression in a cell throughout the cell division, to its daughter cell and bookmarking is important for sustaining the phenotype in a lineage of cells. Then comes the process of imprinting, in which the information in certain genes is active only when it passes to a child through the sperm or the egg, this system of being copied according to the paternal or maternal origin of a gene copy is called genetic imprinting. Third process of epigenetic is paramutation, which is an interaction between two alleles of a particular locus, resulting in a heritable change of one allele that in induced by the other allele. Next process is called gene slicing, it is a process of cutting the DNA for a gene to add base pairs done chemically by restriction enzymes that act as the scissor to cut the DNA.
Another process stated by the article Epigenetics is called chromosome X-inactivation which is also known as lionization, it is a process by which one of the two copies of x chromosome available in female mammals is inactivated by packaging into transcriptional inactive heterochromatin. Another process discussed in the article was Effects of teratogens is very common during pregnancy for mothers that take alcohol and tobacco during their pregnancy. Exposure to some teratogens, even in little amounts, can have disturbing effects.Â Some teratogens are good until they build to extreme concentration levels in the mother and then their effects are seen.Â Some teratogens are dangerous throughout a pregnancy and some are dangerous only at specific points of embryonic development.
According to Epigenetics there are certain mechanisms for epigenetics. One of the mechanisms is DNA methylation and chromatin remodeling, "theÂ phenotypeÂ of a cell or individual is affected by which of its genes are transcribed, heritableÂ transcription statesÂ can give rise to epigenetic effects. There are several layers of regulation ofÂ gene expression. One way that genes are regulated is through the remodeling of chromatin. Chromatin is the complex of DNA and theÂ histoneÂ proteins with which it associates. Chromatin remodeling is accomplished through two main mechanisms (pg 47.)" so as the author stated that there are 2 different ways for chromotin remodeling, first one is the post translational modification of the amino acids that are the basis of histone proteins.
So if the amino acids that are in the chain are altered, the shape of the histone sphere might be changed as well. Since DNA is not completely unwound during duplication. It is possible, that the modified histones may be carried into each new copy of the DNA. So by changing the shape of the histones it would make certain that a differentiated cell would stay differentiated, and not convert back into a stem cell. Another way of chromatin remodeling is by adding a methyl groups to the DNA mostly at Â regions ofÂ DNAÂ where aÂ cytosineÂ nucleotideÂ occurs next to aÂ guanineÂ nucleotide in the linear linnearÂ sequenceÂ ofÂ basesÂ along its length to convert cytosine to mythylcytosine. Basically methylcytosine performs similar role of a regular cytosine, by pairing up with a guanine. However, some areas of genome are methylated more deeply than others and highly methylated areas lean to be less transcriptionally active.
According to Epigenetics Another mechanisms of epigenetics is RNA transcripts and encoding the proteins. "Sometimes a gene, after being turned on, transcribes a product that basically maintains the activity of that gene ( pg.48)." As the author explained that Â RNA signaling includes differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development.Â Other epigenetic changes are mediated by the production of differentÂ splice formsÂ ofÂ RNA, or by formatting a double-stranded RNA. Offspring of the cell in which the gene was turned on will inherit this activity, even if the original stimulus for gene-activation is no longer present. These genes are most often turned on or off byÂ signal transduction, although in some systems requireÂ gap junctions.Â
Another mechanism according to the book Epigenetic is fungal prions. Basically prions are proteins that fold into discrete units which perform distinct cellular functions
But the proteins that can form an infectious conformational state is called prions. However " Fungal prions are considered epigenetic because the infectious phenotype cause by the prion can be inherited without modification of the genome. Prions can have a phenotypic effect through the sequestration of protein in aggregates, thereby reducing that protein's activityâ€¦â€¦â€¦â€¦â€¦.. which results in suppression ofÂ nonsense mutationsÂ in other genes. (pg. 49.)"
According to Halyley Mann Prions are classified as epigenetic regulators because they are able to modify gene expressionÂ through proteinÂ interactions, as opposite to first receiving instructions provided by nucleic acids. As with viral and bacterial pathogens, prions are capable of replication.Â Â However, they do so with no involvement of nucleic acids.Â Â Prions instead of converting into native forms, it turns it into more prions.Â Furthermore, prions come in different strains and even exhibit differential specie host preferences. Then during prion pathogenesis, the initial form of the protein is converted to the insoluble amyloid conformation.Â Â These amyloids make collection of fibrous proteins which eventually direct to amyloidosis and which turn into taxic neurodegenerative symptoms. So basically there are many mechanism of epigenetic.
According to the book Epigenetics certain environmental and dietry factors are the cause to abnormal changes in epigenetic pathways. One of the environmental factor discussed in this book was usage of heavy metals. Heavy metals like camium can disturb DNA methylation which of course is an important part of normal organsimal development and cellular differntation in higher organisms. Then comes the next factor, which is the wide use of pesticide. One of the examples of using pesticide is using vinclozoling, it is a pesticide that can alter DNA methylation with its exposure.
These changes persist in unexposed offspring through several generations.
Then comes the most important one which mostly people ignore is smoking tobacco, "maternal cigarette smoking during pregnancy is related with poor fetal outcome and abnormal miRNA expression is related with unfavorable pregnancy outcomes and variations in brain and behavior in adolescence. Epigenetic mechanisms may mediate some of the consequences of PEMCS through methylation of deoxyribonucleic acid in genes important for brain development, such as the brain-derived neurotrophic factor (pg. 64)." And according to one of the study done in the book Epigenetic states that compared with never smokers, women who first started to smoke during follow-up had an increased risk of acquiring methylation of p16. It also reveals, for the first time, that the relationship between starting to smoke and the subsequent appearance of an epigenetic change."
Also according to Med India's article Molecular basis of epigenetics The link between smoking and cancer has been established for decades. Smoking is the single biggest cause of cancer in the world, and years of research have confirmed that carcinogenic substances in tobacco smoke can damage DNA. Also Exposure to tobacco constituents during early development remains a common but avoidable toxic exposure, which has been clearly linked with decreased lung growth and subsequent wheezing illness. There is also rising evidence that tobacco smoke can influence early immune function.Â Although parental smoking may not be the primary factor in the changing prevalence of asthma and respiratory disease, research propose that it is an important contributor, with significant potential to interact with other genetic factors and environmental risk factors to influence disease tendency. This review explores the consequences of smoking on these important aspects of early development, including potential mechanisms, interactions with influencing asthma genes and a potential role in epigenetic regulation.
According to the book Epigenetics cancer is a muti step process in which genetic and epigenetic errors accumulate and transform a normal cell into an invasive or metastatic tumour cell. Epigenetic changes have been observed in virtually every step of tumor development and progression. Too little DNA methylation which is also known as hypomethylation is believed to initiate chromosome unsteadiness and activate oncogenes. On the other hand, too much DNA methylation which is known as hypermethylation may initiate the silencing of tumor suppressor genes. In inherited cancer syndromes this approach has proved successful.Â Additionally, mutations early in the genesis of common cancers have also been identified and these are likely to be associated with tumour initiation.Â In contrast, few specific genetic mutations have been linked to tumour progression, leading to the suggestion that epigenetic changes may be involved. Epigenetic changes occur without a change in the DNA sequence and they can be induced by various factors.Â
Thus it is possible, for example, that a DNA mutation leads to cellular transformation, but induced changes in the epigenome of the transformed cell enhances the probability that it will be capable of metastasisingÂ In this situation, a genetic mutation initiates the cancer but epigenetic change supports its development.
Epigenetic processes may also be involved in cancer initiation.Â It is possible that epigenetic change may lead directly to cancer initiation Alternatively, changes already encourage within the epigenome may make a copy of cells in such a way as to promote cellular transformation upon a subsequent DNA mutagenic event.Â In this case the epigenetic component of the cancer initiation is related with the genetic component.Â The involvement of epigenetic change in cancer initiation is of course not mutually exclusive to it having also a role in cancer development.
According to David Rodnhiser and Mellisa Mann "Both increases and decreases in DNA methylation are associatedÂ with the aging process, and evidence is accumulating that age dependentÂ methylation changes are involved in the development of neurologicÂ disorders, autoimmunity and cancer in elderly people.Â MethylationÂ changes that occur in an age related manner may include theÂ inactivation of cancer related genes. In some tissues, levelsÂ of methylated cytosines decrease in aging cells, and this demethylationÂ may promote chromosomal instability and rearrangements, whichÂ increases the risk of neoplasia which is the abnormal proliferation ofÂ cells.In other tissues, such asÂ the intestinal crypts, increased global hypermethylation mayÂ be the influence event that accounts for the increased riskÂ of colon cancer with advancing age." So basically It has been shown that the process of aging involves some epigenetic pathways that have been identified in the process of carcinogenesis which is basically a creator of cancer.
David and Mellisa also states that the activation of the immune response involves stepwise epigeneticÂ changes, which allow individual cells to mount a specific immuneÂ response that can be maintained over multiple cell generations
Importance of epigenetics. Also the role of epigeneticÂ errors in the development of complex adult psychiatric, autisticÂ and neurodegenerative disorders. David and Melissa stated that related schizophrenia and mood disorders with DNA rearrangementsÂ that include the DNMT genes. whereas hypermethylation has been shown to repressÂ expression of Reelin which is a protein required for normal neurotransmission,Â memory formation and synaptic plasticity in brain tissue fromÂ patients with schizophrenia and patients with bipolar illnessÂ and psychosis.Â
According to the book Epigenetics, epigenetic in multicellular organisms is generally thought to be a mechanism involved in differentiation, with epigenetic patterns reset when organisms reproduce, there have been some observations of transgenerational epigenetic inheritance Although most of these multigenerational epigenetic traits are gradually lost over several generations, the possibility remains that multigenerational epigenetics could be another aspect to evolution and adaptation. Epigenetics helps to understand how enormous variations originated and evolved into present days life.Alterations in sequence at DNA level such as addition, deletion, reshuffling of sequences and rearrangement of chromosomes are essential tools for creating variation upon which natural selection acts. Besides these , mutation also does its role in evolution by creating heritable change in chromosomes.
In conclusion, the role of epigenetic and environment plays a great role in development and evolution, because as David stated that "It has profound implications in aging, neurological disorders, and child development. Epigenetics could prove more important than genetics for understanding environmental causes of disease. Cancer, atherosclerosis, Alzheimer's disease are all acquired diseases where the environment very likely plays an important role, And there's much more potential for the epigenome to be affected â€¦ than the genome itself." NEEDS THE CLOSING LINE: CONSUT AQSA