Epigenetics why it is important

Those individuals with a high-expression genetic polymorphism are spared any effects, but those with the low-expression variant have MAO-A levels that dip below a key threshold, resulting in a tendency to be violent in later life.

Nevertheless, at present these ideas remain untested and are purely theoretical. In this review we have begun to address the contribution of epigenetic mechanisms to brain function, and consequently dysfunction in the form of neuropsychiatric disorders.

In the classical sense epigenetics describe the machinery and process involved in regulating gene expression, particularly during development. In this respect we have outlined a sub-group of genes, namely those subject to genomic imprinting, for which the epigenetic control is very important and when this goes wrong can result in clinical conditions. Although it is not entirely clear at present, work from animal studies suggests that imprinted genes play an important role in the brain and may well contribute more generally to neuropsychiatric disorder in humans.

In addition to pre-programmed gene regulation, there is a growing body of evidence suggesting that epigenetic mechanisms may also provide a molecular memory of environmental experiences.

This has been clearly shown in animal models 35 and indicated in studies of human twins. However, alterations to the epigenetic code may not result in gross changes in gene expression per se , but provide an additional level of molecular information. A good example of this has been provided by studies of acute and chronic cocaine use in rats. These drug regimens give rise to subtly different histone modifications around the promoter of the FosB gene, 41 but not differences in expression per se.

Although clearly epigenetic mechanisms are of potential clinical relevance, a key question is whether they are accessible to pharmacological intervention. It is hoped that the ongoing epigenome project 37 and the development of more specific drugs may address these issues. Google Scholar. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. What is epigenetics? Developmentally programmed epigenetic modification: imprinted genes. Labile epigenetic mechanisms in the brain. Epigenetics: what is it and why is it important to mental disease? Isles , Anthony R. Oxford Academic. Lawrence S.

Cite Cite Anthony R. Select Format Select format. Permissions Icon Permissions. Abstract Introduction. Open in new tab Download slide. Google Scholar Crossref. Search ADS. Completion of mouse embryogenesis requires both the maternal and paternal genomes.

The course and outcome of psychiatric illness in people with Prader-Willi syndrome: implications for management and treatment. Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication.

Google Scholar PubMed. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Culture of preimplantation embryos and its long-term effects on gene expression and phenotype. Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction. Another case of imprinting defect in a girl with Angelman syndrome who was conceived by intracytoplasmic semen injection.

Intracytoplasmic sperm injection may increase the risk of imprinting defects. Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study. Assisted reproductive therapies and imprinting disorders—a preliminary British survey. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. This allows the transfer of epigenetic marks from mother cells to daughter cells in somatic tissue.

This explains how these marks can be maintained in an individual, but not how they are spread to the next generation of offspring. As can be seen in A the original chromosome contains epigenetic marks on both chromatids, and in B both daughter chromosomes contain some of the epigenetic marks of the mother chromosome due to the semi-conserved nature of mitosis. These marks can also be conserved in their daughter chromatid during meiosis, resulting in all gametes carrying the epigenetic marks of the individual of origin.

However, many of these marks are removed during the process of gamete formation. Methylation marks can be inherited from either the maternal Giuliani et al. Through the father, the offspring can inherit a wide array of methylation marks, with the majority of these marks in some way affecting the digestive systems of the child Soubry, For an example of this deleterious nature of hypomethylation one can look at the Dutch Winter of Hunger, a well-documented example of famine in the modern world that occurred from to due to a blockage preventing the movement of fuel and food in the Netherlands.

This starvation resulted in the hypomethylation of the IGF-2 gene, the gene responsible for the formation of insulin-like growth factor 2. The ability of parental malnutrition to affect the epigenome of the offspring in an overtly negative and harmful way will be examined more closely later in the review. This was very useful and advantageous for nomadic peoples and a case study of this can be seen in the comparison of the Oromo peoples and the Amhara peoples of Ethiopia Alkorta-Aranburu et al.

In this case it appears that epigenetic marks actual favour immunological variation within the newly arrived population. This will be examined in more depth as part of the Case studies section later in the review.

This will eventually result in a population that is genetically similar to the original settlers but will be more adapted to their surrounding environment. To understand the impact epigenetics has had on our development into modern humans we have to compare the areas of gene methylation seen in our species and our closest living relatives. Many of the regions in the human genome that are methylated are not genes that are unique to humans, with the biggest differences in methylation occurring in regions of DNA involved with Transcription Factors or TFs and gene control Hernando-Herraez et al.

This is because TFs have a wide-reaching influence on the expressed phenotype of an individual due to these factors functioning as a form of gene expression regulation, therefore promoting or suppressing other genes in the genome.

Even small differences in the epigenome surrounding TFs can result in widely varying phenotypes between individuals of the same species due to their wide-reaching influences Heyn et al. So it can only be assumed just how important these phenotypic changes are in the variation that separates us from our ancestor species. HARs are regions of DNA that have undergone rapid changes since the emergence of the human species far and above the normal rate of mutation.

These regions stand out due to the extremely accelerated rate of mutations they have undergone and are widely understood to be responsible for the speedy divergence of humans from other species Hubisz and Pollard, The exact nature of the role played by epigenetic changes in HARs is not clear but the importance of their role is undoubtable, with epigenetic changes possibly predating sequential changes in DNA Badyaev, A suggested theory is that these marks actually promoted the occurrence of mutations in the genes that are responsible for our species existence.

Studying the epigenomes of our related species sheds light on the relatively large divergence that has occurred since our emergence from our distant cousins, a divergence of such stature that it cannot be solely explained by nucleotide changes Hernando-Herraez et al. It has even been speculated that epigenetic changes could be more impactful on the Darwinian evolution of a species than genomic mutations Badyaev, and this area of research only adds more weight to these claims.

Modern humans have survived and thrived in a wide array of environments for thousands of years, from the Arctic tundra to Saharan deserts. The key to this success has always been the uniquely human ability to adapt quickly and epigenetics has played a role in this capacity to adapt.

While cultural adaptations to environments, such as changes in clothing or ritualistic behaviour, are the most visual signs of this adaptability, no less important are the more subtle genetic and epigenetic changes that a population undergoes as they live in an area for generations. For example a population that has lived in an arid environment will carry many genetic mutations that make them more suitable to a dry climate. If a catastrophic climate shift occurs and their ancestral lands suddenly become cold and damp they can adapt to wear thicker clothing Cavalli-Sforza and Feldman, to protect against the cold and may even take on new customs and rituals around hygienic behaviour to protect against new diseases that have taken root in the region Wiesenfeld, This population will however still carry many of the genetic mutations that made them suited to their old environment until selection pressure allows new mutations to compensate for these genetic relics.

An important idea is the way in which to consider each different type of adaptation in comparison to one another. Cultural adaptation is a catch all term that encompasses all artificial adaptations an individual can pick up to become more comfortable in an environment Cavalli-Sforza and Feldman, In comparison genetic changes, such as the prevalence of Sickle Cell Anaemia in regions prone to malaria outbreaks, represent much longer term adaptations.

These changes take longer to gain and cannot as easily be shaken off once their usefulness has run its course, such as an individual simply changing their attire to suit the weather Laland, Odling-Smee, and Myles, What do epigenetic changes represent in this model then? Firstly they exemplify medium-term adaptations, falling between cultural changes and genetic evolution in the time it takes an individual to acquire them Giuliani et al. In this model of understanding human adaptation epigenetic changes also serve as a time-keeping mechanism, helping to mitigate the negative effects of genetic relics acquired by ancestor populations under different evolutionary pressures Badyaev, By silencing older genes that once served a vital purpose epigenetics also helps to prevent the build-up of complexity in an organism, silencing older, less frequently transcribed genes Badyaev, , much in the same way that DNA methylation combats the damage caused by transposons Slotkin and Martienssen, A good way to examine this model of adaptation is to consider the way each of these changes would affect a hypothetical population that has suddenly become exposed to a harsh, cold climate.

Very quickly, this population will adapt, first by increasing their protection against the elements by wearing thicker clothes.

While this is an effective method of staying warm their bodies have not yet adapted to the cold, and so, their genes controlling homoeostasis will still function in the same way as they had in a warmer climate, something that might be considerably wasteful and possibly deleterious. Where once their perspiration would help keep the heat from damaging their bodies it now wastes water.

At this stage, after a considerable number of generations, epigenetic changes will begin to take affect under selective pressure. DNA methylations and histone modifications will accumulate, fine tuning their homoeostatic gene expression to the colder environment. This results in the silencing of genes that were better suited to the hotter climate and promotes the expression of other genes that confer an advantage in this colder one.

Finally, after even more generations new alleles will take hold in the populations that represent novel genes. These novel genes will encode new proteins that in some way will provide a selective advantage that is near permanent in expression, if not in providing an advantage. Another point highlighted by this model is that the longer an adaptation takes to be acquired the less likely it is to ever be lost.

After all, it is much easier to take a jacket off than to spontaneously lose a gene responsible for increasing metabolic activity. Epigenetics comes in yet again at this point as not only does it silence older genes that are no longer required, under the influence of selective pressure, it also introduces more plasticity into the expression of genes Giuliani et al. Through this mechanism epigenetics allows the variability of phenotypes that are required for adaptation and selection Tobi et al.

An interesting examination of epigenetics that provides an example of its role in human evolution is a study into the different epigenetic markers between the Oromo and Amhara peoples of the Ethiopian highlands, which revealed something surprising: researchers expected to find that individuals of the Oromo peoples, who are migrants to the highlands, would have an increase in epigenetic marks around genes associated with oxygen uptake or red blood cell production.

These are adaptations that the Amhara peoples already had, allowing them to live successfully in their elevated homeland. Instead many of the epigenetic markers the researchers found in the Oromo population were around genes associated with the immune system Alkorta-Aranburu et al.

More interesting was that these marks were not uniform throughout the population and instead varied widely from person to person Alkorta-Aranburu et al. This appears to show epigenetic marks acting as a catalyst for the introduction of variation in gene expression, resulting in a wide range of phenotypes and responses to combat the new microbiological threats that the migrating population were exposed to upon arriving in the region.

Here, these epigenetic marks are compensating for the lack of immunological adaptation the Oromo peoples have for this new climate compared to the native Amhara people, mitigating the damage done to the Oromo populations in the interim before a genetic mutation could occur that provides stronger protection.

As discussed earlier epigenetics plays a key role in the dietary adaptation individuals carry, producing an individual who carries epigenetic marks that make them more suited to the diet of their parents. Lactose tolerance is one of the ways this epigenetic digestive adaptation manifests Ingram et al. With the increasing availability of dairy products worldwide, the epigenetic modification that produces a weaker tolerance to lactose can only be expected to increase, at least until the lactose tolerance mutation proliferates into the global gene pool.

Various genetic conditions affect red blood cells and their ability to uptake oxygen. These include Sickle Cell Anaemia and Thalassaemia, both of which only occur once the switch to adult haemoglobin is complete in an individual Sripichai et al.

In the case of Sickle Cell Anaemia it is known that the condition confers a resistance to Malaria. With anti-Malaria treatments becoming more and more efficient and mosquito culling beginning to keep infection rates under control it has become a condition that now mostly serves to burden fledgling health services around the world.

As the selective pressure on these populations has changed, the epigenome of these populations has also reacted. POFH is a condition where an individual never undergoes the switch to adult haemoglobin, and thus avoids expressing the Sickle Cell Anaemia and Thalassaemia mutations.

While they still carry these mutations these individuals do not express the deleterious phenotypes due to epigenetic markers that inhibit the associated genes. This is illustrated in Fig. A shows what occurs in an individual who carries the mutations but does not have any epigenetic marks silencing the Adult Haemoglobin Switch Gene. These individuals will eventually develop Sickle Cell Anaemia.

The outside world is continually impinging on us in ways that change how our genes are expressed. When we cut ourselves, for example, genes for making new skin cells are turned on. When we learn to play the violin, gene expression in our brain changes.

A far more controversial claim — made by some writers and scientists — is that epigenetic changes may be inherited across generations. To evolutionary biologists, this raises the specter of Lamarckism. This notion, espoused by the naturalist Jean-Baptiste Lamarck in the early s, is that experience acquired in one generation can be passed on to the next and account for the evolution of new adaptations.

According to Dr. Goll, there are few clear examples of trans-generational epigenetic inheritance described in mammals. There may be a few spots, she notes, where methylation marks are harder to erase than others, permitting some small amount of germline epigenetic inheritance. You may need to change the verbiage under the photo of the calico cat, because calicos are not always femle.

And here is why Because the X chromosome is responsible for both orange and black fur, female cats can display both colors because they have two X chromosomes.

But males, having only one X chromosome, can be either orange or black. For a male cat to have a calico pattern, the feline has to have three sex chromosomes: two Xs and a Y. This XXY combination can occur when there's an incomplete division of the male's XY chromosome pair at the time of fertilization — and it doesn't just happen in cats. It can occur in people too, resulting in a genetic disorder known as Klinefelter syndrome. For felines it is a 1 in 3, occurrence, but it can occur.

So to state that calicos are always female is not exactly factual.