- Josh Choi (joshchoi95@yahoo.com)
Monday, March 19, 2012
The Evidence
According to Manel Esteller in footnote 159, epigenetic differences "help show how environmental factors can change one's gene expression and susceptibility to disease" (346). In this case, is it possible to alter one's epigenome in such a way to prevent gene expression of disease causing genes such as oncogenes? If so,what would such a process entail? How can epigenetic variation be used to explain how in a pair of identical twins one may acquire one disease while the other does not? Finally, how does the idea of epigenetic variation challenge traditional Darwinian Evolution? Relate your answers to eukaryotic gene regulation, make sure to include histone modifications discussed in Section 18.2 of Campbell, and the theme of relationship between structure and function.
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By altering the DNA methylation pattern with epigenetic inheritance, there is possibly a way to prevent genes from being expressed such as oncogenes. Alterations in normal patterns of DNA methylation are seen in some cancers, where they are associated with inappropriate gene expression (Campbell 358). In this case, epigenetic inheritance, the inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence, plays a key role in affecting gene expression regulation as chromatin modifications, for example, can be reversed and may be passed along to a future generation of cells. One example of using chromatin modification is in Drosophila, where experiments suggested that particular histone modifying enzymes recruits DNA methylation enzymes to one region and that the two enzymes work together to silence the specific set of genes (Campbell 358). Through these experiments we can conclude that epigenetic differences "help show how environmental factors can change one's gene expression and susceptibility to disease” (346). The modifications to chromatin through epigenetic inheritance can possibly silence oncogenes by changing the pattern of DNA methylation so that the appropriate gene expression is exhibited.
ReplyDeleteEpigenetic variation is based on the fact that genes are regulated based on interactions with the environment.” A small but significant proportion of all CpG islands (Nucelotides) become methylated during development” (http://genesdev.cshlp.org/content/16/1/6.full), and as one develops, the modifications of chromatin regulate gene expression. With two identical twins, epigenetic variations explain why one identical twin acquires a genetically based disease, but the other does not despite the similar genomes. As they develop and are exposed to a different set of environmental factors, their gene regulation is separate and their molecular systems for chromatin modification interact with each other and are regulated in different ways. The result of DNA methylation can silence the genetically based disease in one twin, while the other one might have a different pattern for DNA methylation due to epigenetic variation and never acquire the genetically based disease.
The idea of epigenetic variation challenges simple Darwinian evolution by challenging the idea that those with the more fit genes will survive and reproduce. But in the case of epigenetic variation, there is an inheritance of traits not directly involving the nucleotide sequence and yet they may be passed along to future generations of cells. Also, Darwin supposed that those with bad genes will most likely die out due to natural selection, but DNA methylation can silence a particular gene that would be disadvantageous to the organism. A methlyation pattern permanently regulates the expression of either the maternal or paternal allele of particular genes at the start of development (Campbell 358). So although an organism may have bad genes, they will not necessary be naturally selected to die because they can prevent some genes from expressing their whole lives.
The theme of structure and function is related to the importance of the chromatin’s modification so that the right set of genes is regulated from expression. DNA methylation is essential for long-term inactivation of genes, and if DNA methylation is not in its normal pattern the expression of genetically based diseases or oncogenes would occur. A combination of different molecules can attach to the histones and alter the activity of the DNA wrapped around them.
(Kirk Chiu- krkpchiu@gmail.com)
The sequences of a DNA strand alter a cell’s susceptibility to disease, and epigenetic differences alter expression of this genetic information. By altering the epigenome, scientists would be able to make patients less susceptible to different diseases. While very intricate and hard to carry-out, it is possible to alter the epigenome by means of drugs. For example, doctors giving patients a drug known as temozolomide can help combat glioblastoma by adding methyl groups to DNA, altering the DNA’s epigenome (http://www.genome.gov/27532724#al-8). As Campbell says, “Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is call epigenetic inheritance” (358). Structure of the epigenome relates to the development of DNA in relation to its cellular environment, so twins who share DNA would have different epigenomes. Because histones (part of epigenetic structure) influence gene expression, susceptibility to disease may depend more on developmental patterns than DNA. Environmental and development interaction, as opposed to superior genes, may have a greater influence on becoming sick with cancer, preventing an individual with potentially superior genes from surviving and reproducing, which goes against Darwin’s model of evolution.
ReplyDelete-Kyle Mueting (kylemueting@comcast.net)