The structure of genes and its alterations are studied in genetics. In epigenetics, the modifications of the gene expression that alter the phenotype are studied. What is Genetics — Definition, Fields, Role 2.
What is Epigenetics — Definition, Fields, Role 3. Genetics refers to the study of heredity and the variation of inherited characteristics. Heredity is the biological process by which a parent passes its genetic information to its offspring. Every individual inherits genes from its mother and father.
Hence, gene serves as the basic unit of heredity. The alternative forms of a gene are called alleles. Many organisms have two alleles that can be either homozygous or heterozygous. Some alleles are dominant over the others and determine the phenotypes of a particular organism.
Many genes are made up of DNA. DNA is packaged into the nucleus by forming chromosomes. The organization of genes is shown in figure 1. To maintain normal DNA methylation patterns not to mention adequate DNA synthesis and healthy development , we need a number of nutrients from our diet, including a source of methyl groups such as methionine an amino acid or choline an ammonium-based molecule, usually grouped with the B-complex vitamins and folate folic acid, found in leafy greens, legumes and oranges.
Although folate is not itself a methyl donor, it interacts with methionine and choline to ensure adequate DNA methylation throughout the genome.
Can your grandma's diet affect you? How could your grandma's diet while pregnant have an affect on generations down the line? There are other studies that have found extremely interesting potential epigenetic impacts upon our emotional wellbeing. However, these studies need to be carefully interpreted. Many of them are conducted on animal models and it is unclear if they can be extrapolated to humans.
Other fairly small scale studies have claimed that the traumas suffered by one generation can leave epigenetic markers that are passed down through the generations—things like an inherited response to stress in the children of Holocaust survivors , and lower cortisol levels in the children of women who were pregnant at the time of the September 11 terrorist attacks and developed post-traumatic stress disorder as a result of the attacks.
Although this idea is intriguing and appealing on various levels, we must be careful to not overblow these findings and apply them in a broad brushstroke manner, especially before more studies have provided further evidence. Many established scientists remain sceptical. Some of the most compelling experiments examining emotional epigenetics effects looked at the mothering habits of rats.
When attentive mothers adopted the pups of inattentive mothers, the rats grew up happier, suggesting that the result was not due to an underlying genetic difference. To further clinch their hypothesis, the researchers gave pups of inattentive mothers a dose of a drug that removes methyl groups, which resulted in these rats not showing the negative impacts of the poor mothering, and their brains free of the epigenetic methylation.
This was because of the epigenetic influence of the mothering behaviour upon the baby rats at a crucial time of their development—shortly after birth is when their hypothalamic-pituitary-adrenal HPA axis develops. This is the hormonal pathway that controls the glucocorticoid receptors.
The additional layer of instructions provided by epigenetic marks is critical to the regulation and control of our genetic information, with implications not only in basic cell development and differentiation, but also disease and other physical conditions. DNA is a long molecule with a 'double helix' structure. The process of cell differentiation is a prime example of epigenetics — an extra layer of information regultates the DNA in our body's cells to create all the different cell types of our body.
DNA A long molecule that is made up of nucleotide bases, carbon sugar molecules and phosphate molecules. To make the twisted ladder shape of the DNA double helix, the nucleotide bases pair up to make the rungs, with the sugar and phosphate molecules along the sides.
There are four nucleotide bases: adenine, thymine, guanine and cytosine. RNA A single stranded molecule that is copied from DNA and also made of nucleotide bases, sugar molecules and phosphate groups. There are several different types of RNA that each have a different function. Histone modification The DNA within the cell nuclei is not just one super-long molecule all tangled up like a ball of string. DNA is coiled around histones, creating structures called nucleosomes.
DNA methylation A methyl group can also attach to the DNA double helix with a different purpose to histone spacing regulation. Regions of the genome that contain CpG islands tend to be promotoer regions for genes, and if these CpG islands are methylated, the gene will be silenced. Inheritance of DNA methylation Generally, the DNA methylation pattern across our genome is a stable, lasting epigenetic marker, set early in development.
This is down to X-chromosome inactivation. The skin of these cats is composed of patches of cells where either the maternal or paternal X chromosome is inactivated.
This results in skin with the O gene switched on and o silenced in some patches orange fur and o gene on and O silenced in other patches black fur , hence the tortoiseshell pattern. Since the male cats only have one X chromosome, and no X-chromosome inactivation, they are either orange or black all over. Epigenetic inheritance, can epigenetic states be passed from one generation to the next? As we have seen from the roundworm example, epigenetic effects in this case extended lifespan can sometimes be passed from one generation to the next, although the effects only seem to last for a few generations.
Are there examples where epigenetic effects carry over to subsequent generations in humans or other mammals? There is some evidence that the effects of the Dutch Hunger Winter affected grandchildren of women who were pregnant during the famine.
Similarly, in a study of a 19th century northern Swedish population who underwent cycles of famine and plenty, the amount of food available appears to have affected the health and longevity of the next generation.
Perhaps the best known example of transgenerational epigenetic effects is provided by the mouse Agouti gene. This gene controls hair colour, and is switched on at just the right time in hair follicle cells to produce a yellow stripe in the otherwise dark hairs, resulting in what is called an agouti coat. But mice with a particular variant of the Agouti gene called Avy have coats that are anywhere between yellow and the normal dark agouti pattern of wild-type mice.
The yellow mice also become obese and suffer other health problems. So the Avy gene seems to have a variable effect in fact the Avy stands for Avariable yellow. How this works has puzzled geneticists for years, but we can now recognise this as an epigenetic effect.
The yellow fur occurs because Avy version of the Agouti gene has faulty controls and is switched on all the time. However, methyl tags are often added to the faulty control DNA sequence and this tends to switch the gene off, resulting in mottled or dark agouti fur in individual mice. Pups born to dams with the Avy gene range in colour from yellow to dark, but the proportion depends on the coat colour of the mother; litters of dark agouti females are more likely to contain dark pups. Furthermore, a higher proportion of dark offspring is observed if both the mother and the grandmother have the dark colouration.
So the agouti colouration, which is determined epigenetically by the number of methyl tags on the Avy gene can to some extent, carry through from one generation to the next.
Although we can find cases where epigenetic effects apparently last from parents to offspring, this is not usually the case and almost all of the epigenetic switches or marks are reset in germ cells eggs and sperm and in the very earliest stages of development of an embryo. Shortly after fertilisation, a developing human embryo consists of a ball of cells called embryonic stem cells. Each of these cells has the capacity to give rise to any of the types of cells in the body as the embryo grows for example, brain cells, skin cells or blood cells.
By contrast, 9 months later when a baby is born, most of the cells making up his or her body are committed to be a specific type of cell with specific functions.
So as the cells divide, the ball of embryonic stem cells gradually develops into all the cell types and structures of the baby at term. For this to happen, thousands of genes must be switched on or off at just the right times and in the right cells as an embryo grows. For example, genes that make the fibrous keratin protein that gives our skin its strength, are only switched on in skin cells and not in the developing brain and genes required for brain cells to develop and make their interconnections are on in the brain but not in the skin.
Epigenetic tags help with this. A very big area of research today concerns how all this gene switching on an off works, and a large part of this process uses the epigenetic chemical tags, especially acetyl and methyl histone tags. In order for those embryonic stem cells to be able to give rise to all of the other types of cells, their epigenetic switches are almost completely reset compared to adult cells.
In February , a sheep called Dolly became the most famous example of her species, briefly even becoming a TV celebrity. The process leading to her birth required a mature oocyte a unfertilised egg from one female sheep and an ordinary cell from the udder of a second sheep. First the nucleus the part containing the DNA was removed from the oocyte.
This was done using a special microscope as although oocytes are quite big compared to other cells, they are still too small to see with the naked eye. Then the nucleus from the udder cell was inserted into enucleated oocyte. No father was involved. Subsequently the same process has been applied to other species and may have medical uses in generating cells that could repair tissues damaged by injury or disease.
This represents an almost unimaginable amount of information, dwarfing even the human genome project. Alteration of the activity of a protein component of heterochromatin might therefore affect the copy number of the sequence to which it binds.
Dynamism of rDNA and balance of heterochromatic sequence and proteins establishes a situation of heterochromatin homeostasis Figure 2.
Sequences are protected from loss by packaging as heterochromatin. Similarly, excess sequence would revert through loss if there is not sufficient protein to package it for stability.
On the whole, the instability of repeat sequence and the consequence of excess heterochromatin proteins creates multiple states that balance the factors and naturally drives the number of repeat sequences and protein expression to equilibrate.
Of course, any external factors that influence heterochromatin protein activity would be expected to result in induced and heritable changes in repetitive DNA copy number. The rDNA is particularly sensitive to induced copy number polymorphism, since it is affected by nutritional status throughout the lifetime of an organism and rDNA copy number exists in excess of what is required for translational demands, allowing some plasticity in copy number without being unduly disadvantageous.
On the surface, induced copy number polymorphism is similar to epigenetic modification particularly if one cannot easily sequence and assemble repetitious DNAs , and the ability of repeat sequences to change in copy number relatively easily adds the degree of volatility common in epigenetic gene regulation.
Unlike many forms of transgenerational gene regulatory effects, induced copy number polymorphisms are linked to chromosomes, and thus are both heritable and selectable. Unlike epigenetic regulation of imprinted or inactivated chromosomes, induced copy number polymorphisms can be inherited over multiple generations.
But like both transgenerational and epigenetic effects, the role of induced polymorphism is only beginning to be considered in evolution. Such investigation will likely be done in simple organisms, such as Drosophila, that have relatively simple rDNA architecture [ 91 , 92 ]. By contrast, humans have multiple rDNA arrays which change in size frequently [ 93 ], and the complex regulation that renders some arrays active and others inactive means it may be some time before we understand how rDNA polymorphisms and rDNA instability [ 94 ] contribute to phenotypic variance in human population or to disease etiology.
In the case of induced polymorphism, germ cells may be more, not less, sensitive to induced alterations in heterochromatin composition, for three reasons. First, in many cases, gene expression is limited in these cell types. Perdurance of heterochromatin proteins, or the presence of ample gene product to endure fluctuation in gene activity, may be less in these cell types. Second, at least in males, the genome is stripped of most somatic chromatin components in favor of packaging proteins and polyamines.
This may increase the sensitivity of such chromosomes to DNA rearrangements or specifically mark some regions for hypervariability. Third, germ cells naturally undergo recombination at a high rate. It is well established that changes in microsatellite and rDNA copy number occur in meiosis, while the same sequences are relatively stable in mitosis.
Mutations may affect one chroma of heterochromatin and not another [ 96 ]. The five enumerated chromas significantly expand our understanding of chromatin structure, but even those five are likely still a simplification caused by our failure to resolve more subtle differences.
Cumbersome work has detected alterations of repeat sequence copy number in few studies, suggesting that this may be a very widespread form of genetic variation [ 66 , 97 , 98 ]. Peng and Karpen showed an increase in DNA damage repair foci in the heterochromatin of suppressor-of-variegation mutants in diploid cells [ 99 , ].
They did not identify the sequences that were being repaired, but the number and distribution of repair foci in the nuclei indicated that it was not clustered i. This observation suggests that the heterochromatin formed on simple repeats and not just the highly-expressed rDNA also is stabilized by packaging as heterochromatin. As our understanding of what heterochromatin is, and as tools become available to probe it in more surgical ways, we may begin to unravel complex interactions between types of heterochromatin as they struggle to keep each other in check or ally to fend off common enemies.
In the end, all forms of regulation are genetic, and so are salient in understanding how complex, pleiotropic, and epistatic genetic interactions conspire to create phenotypes.
This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Special Issues. Academic Editor: Victoria H. Received 22 Jul Accepted 20 Sep Published 29 Nov Abstract At its broadest sense, to say that a phenotype is epigenetic suggests that it occurs without changes in DNA sequence, yet is heritable through cell division and occasionally from one organismal generation to the next.
Epigenetics and Evolution The importance of sequence polymorphisms in evolution is fundamental and irrefutable. Figure 1. Relationships within genetics: random sequence polymorphisms, epigenetics, gene regulatory mechanisms, and induced polymorphisms. Figure 2. An illustration of a balance between heterochromatic sequences and heterochromatin components e.
Repetitious heterochromatin-forming sequences rectangles are normally in balance with the proteins that bind them circles , package them as heterochromatin, and thereby stabilize them conditions in gray. If the expression or activity of proteins is reduced a , repetitious sequence is exposed, destabilized, and lost through damage-repair, recombination, or extrachromosomal circle formation b , until a new balance is established.
Excess protein has gene regulatory consequence throughout the genome and presses to reestablish balance by altering expression level or activity c or perhaps through repeat expansion d. References N. Youngson and E. Chong, N. Youngson, and E. Maggert and G. View at: Google Scholar K. Gehring, J. Huh, T. Hsieh et al. Wolff, I. Weinhofer, J. Seguin et al. Luo, J. Taylor, A. Spriggs et al.
Kaykov and B. Vengrova and J. Arico, D. Katz, J. Maggert and K. View at: Google Scholar V. Lloyd, D. Sinclair, and T. View at: Google Scholar B. Haller and R. Weiler and B. View at: Google Scholar J.
Nakayama, A. Klar, and S. Dalgaard and A. View at: Google Scholar S. Vengrova, J. Dalgaard, B. Arcangioli, and A. R—R, View at: Google Scholar R. Pimpinelli, M. Gatti, and A. Pimpinelli, G. Santini, and M.
0コメント