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Figure 1 : Identical twin toddlers
Source : ((How Monozygotic Twins Form + Interesting Twin Facts, n.d.)
Identical twins are also named as monozygotic twins. They are formed by the fertilization of a single egg which splits into two.
Figure 2 : Formation of identical twins
Source : (Identical Twins | Talking Glossary of Genetic Terms | NHGRI, n.d.)
When we consider the formation of identical twins, we can see that they share their DNA code with each other. But are they 100% identical? That is where the question comes in. The surrounding, exposures and nutrition are capable in deciding how the genes are expressed (Are identical twins 100% genetically identical? | Genetics Awareness Project at Miller School of Medicine, n.d.).
An argument raised regarding this matter. Nature? Or Nurture? Nature was all about their genetic code. And nurture was about how the identical twins were raised. Many studies have been done by scientists to find out the extent of the effect of nature Vs. nurture on many traits in identical twins. Some traits are affected by nature (DNA), rather than nurture (environment). IQ is an example for that. Just imagine there are identical twins who are separated at birth and raised in two different households. However, their IQ would be almost similar since they share similar genetic code, despite the household that they are raised. Some traits are affected by nurture(environment), rather than nature (DNA). Preference for a political party is a good example for these kinds of traits.
Let us consider identical twins who are raised in the same environment. Their ‘nature’ and ‘nurture’ are almost similar. However, yet they are not 100% identical. These differences can be seen basically in their health or preferences. What is the reason for these differences? That is where the term ‘Epigenetics’ comes in(Epigenetics and the influence of our genes | Courtney Griffins | TEDxOU – YouTube, n.d.).
Basically ‘Epigenetics’ means ‘above’ or ‘top of’ genetics. Epigenetics is all about the external modifications that turn ‘on’ or ‘off’ the genes. These modifications do not change the DNA sequence/genetic code. What they do is, they change how the genes are read by the cells (Epigenetics: Definition & Examples | Live Science, n.d.).
The three main mechanisms involved in generating an Epigenetic signal are,
Covalent modifications E.g.: Phosphorylation, Acetylation
Non-covalent mechanisms E.g.: Chromatin remodeling
- Non-coding RNA
Figure 3 : The process of DNA methylation
Source : ((4) (PDF) Sperm DNA Methylation, Infertility and Transgenerational Epigenetics, n.d.)
Figure 4 : Histone acetylation and deacetylation
Source : (Barnes et al., 2005)
Figure 5 : Histone phosphorylation
Source : (Banerjee & Chakravarti, 2011)
Figure 6 : Chromatin remodeling
Source : (Fig. 1. | Molecular and Cellular Biology, n.d.)
Figure 7 : RNAi pathways in gene silencing
Source : (RNAi Tools for Epigenetics Research | Sigma-Aldrich, n.d.)
Let us understand what is basically happening in these epigenetic mechanisms. In DNA methylation, a methyl group covalently attaches to the C5 position of CpG dinucleotides. CpG methylation is capable of suppressing gene transcription by several mechanisms. The presence of the methyl group at a specific CpG may directly block DNA recognition and binding with transcription factors (Handy et al., 2011).
Deacetylation of histones correlates with CpG methylation and the inactive state of chromatin while acetylation of histones is mostly associated with the promotion of transcription (Handy et al., 2011). A substantial number of phosphorylated histone residues are known to be associated with gene expression (Rossetto et al., 2012). Both histone acetylation and phosphorylation (which are covalent histone modifications), are capable of altering the physical structure of chromatin fibers, which impacts the accessibility to gene expression.
ATP-dependent chromatin remodeling complexes mainly modify chromatin accessibility by altering histone DNA interactions, perhaps by sliding or ejecting nucleosomes (Goldberg et al., 2007).
Non-coding RNA is responsible in controlling multiple epigenetic phenomena. These RNAs usually act with some other components of the cell’s chromatin and DNA
methylation machinery in order to achieve gene silencing(Goldberg et al., 2007).
Now we have a rough idea on the epigenetic mechanisms. Then, what is the link between the dissimilarities in identical twins and epigenetics?
Although monozygotic twins share a common genetic code, we know that are not 100% identical. Several phenotypic discordances can be observed in identical twins. E.g.: differences in susceptibilities to diseases, anthropomorphic features, etc. To study this, a group of scientists have done a study on a large cohort of monozygotic twins. Eighty volunteer Caucasian twins from Spain had been recruited in the study, including 30 male and 50 female subjects. Their mean (±SD) age was 30.6 (±14.2) years (range, 3–74 years). The scientists have studied global and locus specific differences in epigenetic mechanisms such as DNA methylation and histone acetylation. These scientists have revealed, although monozygotic twins are epigenetically indistinguishable during the early years of their life, older monozygotic twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation which had affected their portrait of gene expression. The differences in epigenetic patterns in genetically identical individuals can be explained by the influence of both external and internal factors. Smoking habits, physical activity, or diet are some examples for external factors. These factors have been suggested to have a long-term influence on the alteration of epigenetic modifications.
The differential markers between monozygotic twins are distributed throughout their genomes, which repeat DNA sequences and single-copy genes, and thereby having a crucial impact on gene expression. These epigenetic markers were more distinct in the monozygotic twins who were older, had different lifestyles, and had spent a less time of their lives together. It explains the important role of environmental factors in translating the same genotype into a different phenotype (Fraga et al., 2005).
Keep in your mind that identical twins could be not that identical!
Author: Ayodya de Alwis
Undergraduate – B.Sc (Honors in Immunology and Integrative Molecular Biology)
Faculty of Science
University of Colombo
References: Sperm DNA Methylation, Infertility and Transgenerational Epigenetics. (n.d.). Retrieved June 13, 2020, from https://www.researchgate.net/publication/290396042_Sperm_DNA_Methylation_Infertility_and_Transgenerational_Epigenetics Are identical twins 100% genetically identical? | Genetics Awareness Project at Miller School of Medicine. (n.d.). Retrieved June 13, 2020, from http://gap.med.miami.edu/learn-about-genetics/have-questions-about-genetics/are-identical-twins-100-genetically-identical Banerjee, T., & Chakravarti, D. (2011). A Peek into the Complex Realm of Histone Phosphorylation. Molecular and Cellular Biology, 31(24), 4858–4873. https://doi.org/10.1128/mcb.05631-11 Barnes, P. J., Adcock, I. M., & Ito, K. (2005). Histone acetylation and deacetylation: Importance in inflammatory lung diseases. In European Respiratory Journal (Vol. 25, Issue 3, pp. 552–563). European Respiratory Society. https://doi.org/10.1183/09031936.05.00117504 Epigenetics and the influence of our genes | Courtney Griffins | TEDxOU - YouTube. (n.d.). Retrieved June 12, 2020, from https://www.youtube.com/watch?v=JTBg6hqeuTg Epigenetics: Definition & Examples | Live Science. (n.d.). Retrieved June 13, 2020, from https://www.livescience.com/37703-epigenetics.html Fig. 1. | Molecular and Cellular Biology. (n.d.). Retrieved June 14, 2020, from https://mcb.asm.org/content/20/6/1899/F1 Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., Boix-Chornet, M., Sanchez-Aguilera, A., Ling, C., Carlsson, E., Poulsen, P., Vaag, A., Stephan, Z., Spector, T. D., Wu, Y. Z., … Esteller, M. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America, 102(30), 10604–10609. https://doi.org/10.1073/pnas.0500398102 Goldberg, A. D., Allis, C. D., & Bernstein, E. (2007). Epigenetics: A Landscape Takes Shape. Cell, 128(4), 635–638. https://doi.org/10.1016/j.cell.2007.02.006 Handy, D. E., Castro, R., & Loscalzo, J. (2011). Epigenetic modifications: Basic mechanisms and role in cardiovascular disease. Circulation, 123(19), 2145–2156. https://doi.org/10.1161/CIRCULATIONAHA.110.956839 How Monozygotic Twins Form + Interesting Twin Facts. (n.d.). Retrieved June 12, 2020, from https://www.verywellfamily.com/what-are-monozygotic-twins-1960315 Identical Twins | Talking Glossary of Genetic Terms | NHGRI. (n.d.). Retrieved June 13, 2020, from https://www.genome.gov/genetics-glossary/identical-twins RNAi Tools for Epigenetics Research | Sigma-Aldrich. (n.d.). Retrieved April 13, 2020, from https://www.sigmaaldrich.com/technical-documents/articles/biofiles/rnai-tools-for-epigenetics-research.html Rossetto, D., Avvakumov, N., & Côté, J. (2012). Histone phosphorylation: A chromatin modification involved in diverse nuclear events. In Epigenetics (Vol. 7, Issue 10, pp. 1098–1108). Taylor and Francis Inc. https://doi.org/10.4161/epi.21975
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