Shenk describes the stark differences between identical twins Otto and Ewald, emphasized in the picture of the twins side by side (83). The twins have identical DNA, but their differences can be partially explained by epigenetics. Biologist Manuel Esteller and his colleagues conducted an experiment with 80 sets of identical twins to study the role of epigenetics in trait differences, and they found epigenetic differences in 35% of identical twin sets (346). How do environmental influences alter gene expression in humans through epigenetics? Specifically, how do methylation and acetylation affect DNA organization and gene expression? Looking at the results of Esteller's study, what is the role of epigenetics in developing the differences between identical twins?
Adele Padgett
adele.padgett@gmail.com
It a common misconception enforced by the name itself that identical twins are in fact identical. David Shenk understands that “genetic differences do matter,” but for as much as “we inherit…we also become” (78,83). Identical twins share a common sequence of DNA. After the mother’s egg was fertilized by the father’s sperm, the fertilized egg split off into two distinct diploid organisms. Since this duplication mechanism was by mitosis, the second organism was an exact copy of the first. However, most identical twins are so similar due to their “early shared GXE” and “shared cultural circumstances” (Shenk 80,81). To think that not only the genes are equivalent, but also the uterine environment and nutrition, the home they lived in, the family they group with were equivalent sets up two human beings, with the potential to become very different, end up having many similarities is not surprising. That said, separated at adoption twins Jim Springer and Jim Lewis, had amazing similarities, yet “for every tiny similarity between the Jim twins, there were thousands of tiny (but unmentioned) dissimilarities” (Diaconis qtd. in Shenk 81). Many of the differences that do exist can be accounted for the epigenetic differences. Epigenetics is the “study of heritable changes in gene expression that are not mediated by DNA sequence alterations.13 Because of their inherent malleability, epigenetic mechanisms are susceptible to environmental influences” (http://www.superfund.geneimprint.com/media/pdfs/14698016_fulltext.pdf). Gene expression can be altered by our nutrition. The food we eat can dramatically alter which genes are turned on. For example, the human growth hormone is secreted from the pituitary gland and “stimulates muscles to grow, bones to strengthen and even the growth of internal organs” (http://www.ehow.com/how-does_4759518_human-growth-hormone-work.html). Genetic expression is influenced by hormones as depicted in Diagram B on page 23 in The Genius in All of Us. Since diet can influence the HGH, environment including nutritional habits, can influence gene expression through epigenetics. A diet consisting of the consumption of “large meals with a high glycemic index forces the body to release a high amount of insulin into the system to aid with digestion. This reaction not only forces your body to store fat, it may also inhibit the flow of the growth hormone being released throughout your bloodstream” (http://www.selfgrowth.com/articles/Staff1.html). Since HGH changes gene expression resulting in the transcription of genes that produce proteins that stimulate growth, diet indirectly affects gene expression. In another example, experiences in early childhood can effect gene expression by affecting hormone release. In one study, “Animals exposed to short periods of infantile stimulation or handling show decreased HPA responsivity to stress, whereas maternal separation, physical trauma and endotoxin administration enhance HPA responsivity to stress” (http://content.karger.com/ProdukteDB/produkte.asp?Doi=111396).
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ReplyDeleteThe chemistry of hormones, whether steroids or proteins, have the ability to modify chromatin. Chromatin modifications lead to differences in gene expression. In addition, light can be an environmental influence that affects the epigenome. In a study conducted by biologist Thomas Hunt Morgan with butterflies where he placed caterpillars in different color light, the results yielded that “Exposure to red light resulted in intensely colored wings, while exposure to green light resulted in dusky wings” and “blue light and darkness led to paler colored wings” (http://www.nature.com/scitable/topicpage/environmental-influences-on-gene-expression-536). The different colors of lights must have had some influence on the epigenome of the cells in the butterflies that caused different genes to be transcribed. Therefore, different mRNA were made which yielded different proteins. These differing proteins finally were detected by the visual phenotype of differing wing colors. In 1999, Enrico Coen studied two distinctly different flowers, the Newer “Peloria” toadflax and the Ordinary toadflax. He and others were “astounded to find that the DNA code in each plant was exactly the same” (Shenk 158). There difference therefore wasn’t in genome, but in there epigenome. Epigenome differences can account for distinct physical differences.
Acetylation and methylation play a large role in the epigenome. Histone acetylation which is normally catalyzed by histone acetyltransferases (HATs), is when a –COCH3 group is added to amino acids of the histone proteins. “Acetylation of the lysine residues at the N terminus of histone proteins removes positive charges, thereby reducing the affinity between histones and DNA” which therefore makes the DNA containing genes more accessible to RNA polymerase and transcription factors (http://www.web-books.com/MoBio/Free/Ch4G.htm). It is more likely then the genes will be transcribed into pre-mRNAs. The more pre-mRNAs there are, the more proteins there will be and the more that gene will be expressed. In essence, acetylation converts DNA packaged into heterochromatin into less compact euchromatin so transcription factors can bind to the promoter TATA box of the gene. In a 1964 experiment, it was found that “such modifications of histone structure, acetylation in particular, may affect the capacity of the histone to inhibit ribonucleic acid synthesis in vivo” (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC300163/?page=1). On the other hand, histone methylation is when a –CH3 is added to a cytosine nucleotide. Methylation causes the DNA strand to be wound more tightly around the histone protein making gene expression decrease since transcription factors do not have access to the gene’s promoter region. Methylation and acetylation are important in gene expression of neural cells. In fact, “Some inherited neurological disorders have recently been linked to mutations in genes that regulate DNA methylation, and alterations in DNA and protein methylation and/or acetylation have been documented in studies of age-related neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD)” (http://www.sciencedirect.com/science/article/pii/S1568163703000138).
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ReplyDeleteIn the application of Shenk’s GXE model, our genes are what we have no control over. The sequence of our DNA is decided from a moment in time and every cell in our body has that sequence. However, the environment remains which gives life its unknown, malleable qualities. In reference to Shenk’s analogy, cooks that start out with the same ingredients can bake very different cakes (23). This discrepancy is at least partly because of environmental influence on our epigenomes. This is why identical twins have differences as seen in the Otto and Ewald. An incredible 35% of identical twins were found to have epigenetic differences according to Esteller’s experiment. Epigenomes “serve as a mediator for gene expression, telling genes when to turn on and off” (Shenk 159). Since we are the sum of our proteins, gene expression is directly influential to who we are. It is the epigenetic differences in twin that explains their uniqueness.
Lizzy Ettleson, lettleson@gmail.com