Imprinting (genetics)
Encyclopedia
Genomic imprinting is a genetic
phenomenon by which certain gene
s are expressed
in a parent
-of-origin-specific manner. It is an inheritance process independent of the classical Mendelian inheritance
. Imprinted allele
s are silenced such that the genes are either expressed only from the non-imprinted allele inherited from the mother (e.g. H19
or CDKN1C), or in other instances from the non-imprinted allele inherited from the father (e.g. IGF-2). Forms of genomic imprinting have been demonstrated in insect
s, mammal
s and flowering plant
s.
Genomic imprinting is an epigenetic
process that involves methylation
and histone
modifications in order to achieve monoallelic gene expression without altering the genetic sequence. These epigenetic marks are established in the germline
and are maintained throughout all somatic cells of an organism.
Appropriate expression of imprinted genes is important for normal development, with numerous genetic diseases associated with imprinting defects including Beckwith-Wiedemann syndrome
, Silver-Russell syndrome, Angelman syndrome
and Prader-Willi syndrome
.
s possess two copies of the genome
. Each autosomal gene is therefore represented by two copies, or alleles, with one copy inherited from each parent at fertilisation
. For the vast majority of autosomal genes, expression occurs from both allele
s simultaneously. In mammals, however, a small proportion (<1%) of genes are imprinted, meaning that gene expression occurs from only one allele. The expressed allele is dependent upon its parental origin. For example, the gene encoding Insulin-like growth factor 2
(IGF2/Igf2) is only expressed from the allele inherited from the father.
The phrase "imprinting" was first used to describe events in the insect Nipaecoccus nipae. In Pseudococcids (mealybug
s) (Homoptera
, Coccoidea) both the male and female develop from a fertilised egg. In females, all chromosomes remain euchromatic
and functional. In embryos destined to become males, one haploid set of chromosomes becomes heterochromatin
ised after the sixth cleavage division and remains so in most tissues; males are thus functionally haploid. In insects, imprinting describes the silencing of the paternal genome in males, and thus is involved in sex determination. In mammals, genomic imprinting describes the processes involved in introducing functional inequality between two parental alleles of a gene.
. Nucleus transplantation experiments in mouse
zygotes in the early 1980s confirmed that normal development requires the contribution of both the maternal and paternal genomes. The vast majority of mouse parthenogenones/gynogenones (with two maternal or egg genomes) and androgenones (with two paternal or sperm genomes) die at, or before, the blastocyst/implantation stage. In the rare instances that they develop to postimplantation stages, gynogenetic embryos show better embryonic development relative to placental development, while for androgenones, the reverse is true. Nevertheless, for the latter, only a few have been described.
Parthenogenetic/gynogenetic embryos have twice the normal expression level of maternally derived genes, and lack expression of paternally expressed genes, while the reverse is true for androgenetic embryos. It is now known that there are at least 80 imprinted genes in humans and mice, many of which are involved in embryonic and placental growth and development. Various methods have been used to identify imprinted genes. In swine, Bischoff et al. 2009 compared transcriptional profiles using short-oligonucleotide microarrays (Affymetrix Porcine GeneChip) to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome) An intriguing study surveying the transcriptome of murine brain tissues revealed over 1300 imprinted gene loci (approximately 10-fold more than previously reported) by Illumina RNA-sequencing (RNA-Seq) technology from F1 hybrids resulting from reciprocal crosses.
No naturally occurring cases of parthenogenesis
exist in mammals because of imprinted genes. Experimental manipulation of a paternal methylation imprint controlling the Igf2 gene has, however, recently allowed the creation of rare individual mice with two maternal sets of chromosomes - but this is not a true parthenogenone. Hybrid offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes.
rather than DNA sequence). In germline
cells the imprint is erased and then re-established according to the sex
of the individual; i.e. in the developing sperm (during spermatogenesis
), a paternal imprint is established, whereas in developing oocytes (oogenesis
), a maternal imprint is established. This process of erasure and reprogramming
is necessary such that the current imprinting status is relevant to the sex of the individual. In both plants and mammals there are two major mechanisms that are involved in establishing the imprint; these are DNA methylation
and histone
modifications.
s and differentially methylated regions (DMRs). When these regulatory elements control the imprinting of one or more genes, they are known as imprinting control regions (ICR). The expression of non-coding RNA
s, such as Air on mouse chromosome 17 and KCNQ1OT1
on human chromosome 11p15.5, have been shown to be essential for the imprinting of genes in their corresponding regions.
Differentially methylated regions are generally segments of DNA rich in cytosine
and guanine
nucleotides, with the cytosine nucleotides methylated on one copy but not on the other. Contrary to expectation, methylation does not necessarily mean silencing; instead, the effect of methylation depends upon the default state of the region.
n mammals (placental mammals and marsupials) and flowering plants. Imprinting of whole chromosomes has been reported in mealybugs (Genus: Pseudococcus
). and a fungus gnat
(Sciara). It has also been established that X-chromosome inactivation occurs in an imprinted manner in the extra-embryonic tissues of mice and all tissues in marsupials, where it is always the paternal X-chromosome which is silenced.
The majority of imprinted genes in mammals have been found to have roles in the control of embryonic growth and development, including development of the placenta. Other imprinted genes are involved in post-natal development, with roles affecting suckling and metabolism.
Also known as the kinship theory of genomic imprinting, this hypothesis states that the inequality between parental genomes due to imprinting is a result of the differing interests of each parent
in terms of the evolutionary fitness of their genes
. The father
's genes that encode for imprinting gain greater fitness through the success of the offspring, at the expense of the mother
. The mother's evolutionary imperative is often to conserve resources for her own survival while providing sufficient nourishment to current and subsequent litters. Accordingly, paternally expressed genes tend to be growth promoting whereas maternally expressed genes tend to be growth limiting. In support of this hypothesis, genomic imprinting has been found in all placental mammals, where post-fertilisation offspring resource consumption at the expense of the mother is high; although it has also been found in oviparous birds where there is relatively little post-fertilisation resource transfer and therefore less parental conflict.
However, our understanding of the molecular mechanisms behind genomic imprinting show that it is the maternal genome that controls much of the imprinting of both its own and the paternally-derived genes in the zygote, making it difficult to explain why the maternal genes would willingly relinquish their dominance to that of the paternally-derived genes in light of the conflict hypothesis. Several other hypotheses that propose a coadaptive reason for the evolution of genomic imprinting have been proposed.
Others have approached their study of the origins of genomic imprinting from a different side, arguing that natural selection
is operating on the role of epigenetic marks as machinery for homologous chromosome recognition during meiosis, rather than on their role in differential expression. This argument centers on the existence of epigenetic effects on chromosomes that do not directly affect gene expression, but do depend on which parent the chromosome originated from. This group of epigenetic changes that depend on the chromosome's parent of origin (including both those that affect gene expression and those that do not) are called parental origin effects, and include phenomena such as paternal X inactivation in the marsupials, nonrandom parental chromatid distribution in the ferns, and even mating type switching in yeast. This diversity in organisms that show parental origin effects has prompted theorists to place the evolutionary origin of genomic imprinting before the last common ancestor of plants and animals, over a billion years ago.
Natural selection for genomic imprinting requires genetic variation in a population. A hypothesis for the origin of this genetic variation states that the host-defense system responsible for silencing foreign DNA elements, such as genes of viral origin, mistakenly silenced genes whose silencing turned out to be beneficial for the organism. There appears to be an over-representation of retrotransposed
genes, that is to say genes that are inserted into the genome by virus
es, among imprinted genes. It has also been postulated that if the retrotransposed gene is inserted close to another imprinted gene, it may just acquire this imprint.
, with clones having DNA that is not methylated
in the correct position. It is possible that this is due to a lack of time for reprogramming to be completely achieved. When a nucleus
is added to an egg during somatic cell nuclear transfer
, the egg starts dividing in minutes, as compared to the days or months it takes for reprogramming during embryo
nic development. If time is the responsible factor, it may be possible to delay cell division in clones, giving time for proper reprogramming to occur.
An allele of the "callipyge" (from the Greek
for "beautiful buttocks"), or CLPG, gene in sheep produces large buttocks consisting of muscle with very little fat. The large-buttocked phenotype only occurs when the allele is present on the copy of chromosome 18 inherited from a sheep's father and is not on the copy of chromosome 18 inherited from that sheep's mother.
s to be described in humans were the reciprocally inherited Prader-Willi syndrome
and Angelman syndrome
. Both syndromes are associated with loss of the chromosomal region 15q11-13 (band 11 of the long arm of chromosome 15). This region contains the paternally expressed genes (SNRPN and NDN
) and the maternally expressed gene (UBE3A
).
is a paternally expressed imprinted gene located on chromosome 1 in humans. Loss of NOEY2 expression is linked to an increased risk of ovarian and breast cancers; in 41% of breast and ovarian cancers the protein transcribed by NOEY2 is not expressed, suggesting that it functions as a tumor suppressor gene
Therefore, if a person inherits both chromosomes from the mother, the gene will not be expressed and the individual is put at a greater risk for breast and ovarian cancer.
, Silver-Russell syndrome, and pseudohypoparathyroidism
.
Transient neonatal diabetes mellitus
can also involve imprinting.
The "imprinted brain theory
" argues that unbalanced imprinting may be a cause of autism
and psychosis
.
s (angiosperms). During fertilisation of the egg cell, a second, separate fertilization event gives rise to the endosperm
, an extraembryonic structure that nourishes the embryo in a manner analogous to the mammalian placenta
. Unlike the embryo, the endosperm is often formed from the fusion of two maternal cells with a male gamete
. This results in a triploid
genome. The uneven ratio of maternal to paternal genomes appears to be critical for seed development. Some genes are found to be expressed from both maternal genomes while others are expressed exclusively from the lone paternal copy.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
phenomenon by which certain gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s are expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in a parent
Parent
A parent is a caretaker of the offspring in their own species. In humans, a parent is of a child . Children can have one or more parents, but they must have two biological parents. Biological parents consist of the male who sired the child and the female who gave birth to the child...
-of-origin-specific manner. It is an inheritance process independent of the classical Mendelian inheritance
Mendelian inheritance
Mendelian inheritance is a scientific description of how hereditary characteristics are passed from parent organisms to their offspring; it underlies much of genetics...
. Imprinted allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s are silenced such that the genes are either expressed only from the non-imprinted allele inherited from the mother (e.g. H19
H19 (gene)
H19 is a gene for a long noncoding RNA, found in humans and elsewhere. This gene seems to have a role in some forms of cancer.The H19 gene is also known as ASM, ASM1 and BWS, among others....
or CDKN1C), or in other instances from the non-imprinted allele inherited from the father (e.g. IGF-2). Forms of genomic imprinting have been demonstrated in insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
s, mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and flowering plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s.
Genomic imprinting is an epigenetic
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
process that involves methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
and histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
modifications in order to achieve monoallelic gene expression without altering the genetic sequence. These epigenetic marks are established in the germline
Germline
In biology and genetics, the germline of a mature or developing individual is the line of germ cells that have genetic material that may be passed to a child.For example, gametes such as the sperm or the egg, are part of the germline...
and are maintained throughout all somatic cells of an organism.
Appropriate expression of imprinted genes is important for normal development, with numerous genetic diseases associated with imprinting defects including Beckwith-Wiedemann syndrome
Beckwith-Wiedemann syndrome
Beckwith–Wiedemann syndrome is an overgrowth disorder usually present at birth characterized by an increased risk of childhood cancer and certain congenital features. Originally, Dr...
, Silver-Russell syndrome, Angelman syndrome
Angelman syndrome
Angelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....
and Prader-Willi syndrome
Prader-Willi syndrome
Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
.
Overview
In diploid organisms, somatic cellSomatic cell
A somatic cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell...
s possess two copies of the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
. Each autosomal gene is therefore represented by two copies, or alleles, with one copy inherited from each parent at fertilisation
Fertilisation
Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
. For the vast majority of autosomal genes, expression occurs from both allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s simultaneously. In mammals, however, a small proportion (<1%) of genes are imprinted, meaning that gene expression occurs from only one allele. The expressed allele is dependent upon its parental origin. For example, the gene encoding Insulin-like growth factor 2
Insulin-like growth factor 2
Insulin-like growth factor 2 is one of three protein hormones that share structural similarity to insulin.-Gene structure:In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7...
(IGF2/Igf2) is only expressed from the allele inherited from the father.
The phrase "imprinting" was first used to describe events in the insect Nipaecoccus nipae. In Pseudococcids (mealybug
Mealybug
Mealybugs are insects in the family Pseudococcidae, unarmored scale insects found in moist, warm climates. They are considered pests as they feed on plant juices of greenhouse plants, house plants and subtropical trees and also acts as a vector for several plant diseases.-Distribution:Mealybugs...
s) (Homoptera
Homoptera
Homoptera is a deprecated suborder of order Hemiptera; recent morphological studies and DNA analysis strongly suggests that the order is paraphyletic. It was therefore split into the suborders Sternorrhyncha, Auchenorrhyncha, and Coleorrhyncha....
, Coccoidea) both the male and female develop from a fertilised egg. In females, all chromosomes remain euchromatic
Euchromatin
Euchromatin is a lightly packed form of chromatin that is rich in gene concentration, and is often under active transcription. Unlike heterochromatin, it is found in both cells with nuclei and cells without nuclei...
and functional. In embryos destined to become males, one haploid set of chromosomes becomes heterochromatin
Heterochromatin
Heterochromatin is a tightly packed form of DNA, which comes in different varieties. These varieties lie on a continuum between the two extremes of constitutive and facultative heterochromatin...
ised after the sixth cleavage division and remains so in most tissues; males are thus functionally haploid. In insects, imprinting describes the silencing of the paternal genome in males, and thus is involved in sex determination. In mammals, genomic imprinting describes the processes involved in introducing functional inequality between two parental alleles of a gene.
Imprinted genes in mammals
That imprinting might be a feature of mammalian development was suggested in breeding experiments in mice carrying reciprocal translocationsChromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
. Nucleus transplantation experiments in mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
zygotes in the early 1980s confirmed that normal development requires the contribution of both the maternal and paternal genomes. The vast majority of mouse parthenogenones/gynogenones (with two maternal or egg genomes) and androgenones (with two paternal or sperm genomes) die at, or before, the blastocyst/implantation stage. In the rare instances that they develop to postimplantation stages, gynogenetic embryos show better embryonic development relative to placental development, while for androgenones, the reverse is true. Nevertheless, for the latter, only a few have been described.
Parthenogenetic/gynogenetic embryos have twice the normal expression level of maternally derived genes, and lack expression of paternally expressed genes, while the reverse is true for androgenetic embryos. It is now known that there are at least 80 imprinted genes in humans and mice, many of which are involved in embryonic and placental growth and development. Various methods have been used to identify imprinted genes. In swine, Bischoff et al. 2009 compared transcriptional profiles using short-oligonucleotide microarrays (Affymetrix Porcine GeneChip) to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome) An intriguing study surveying the transcriptome of murine brain tissues revealed over 1300 imprinted gene loci (approximately 10-fold more than previously reported) by Illumina RNA-sequencing (RNA-Seq) technology from F1 hybrids resulting from reciprocal crosses.
No naturally occurring cases of parthenogenesis
Parthenogenesis
Parthenogenesis is a form of asexual reproduction found in females, where growth and development of embryos occur without fertilization by a male...
exist in mammals because of imprinted genes. Experimental manipulation of a paternal methylation imprint controlling the Igf2 gene has, however, recently allowed the creation of rare individual mice with two maternal sets of chromosomes - but this is not a true parthenogenone. Hybrid offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes.
Genetic mapping of imprinted genes
At the same time as the generation of the gynogenetic and androgenetic embryos discussed above, mouse embryos were also being generated that contained only small regions that were derived from either a paternal or maternal source. The generation of a series of such uniparental disomies, which together span the entire genome, allowed the creation of an imprinting map. Those regions which when inherited from a single parent result in a discernible phenotype contain imprinted gene(s). Further research showed that within these regions there were often numerous imprinted genes. Around 80% of imprinted genes are found in clusters such as these, called imprinted domains, suggesting a level of co-ordinated control. More recently, genome-wide screens to identify imprinted genes have used differential expression of mRNAs from control fetuses and parthenogenetic or androgenetic fetuses hybridized to expression arrays, allele-specific gene expression using SNP genotyping arrays, transcriptome sequencing, in silico prediction pipelines...to name a few.Imprinting mechanisms
Imprinting is a dynamic process. It must be possible to erase and re-establish the imprint through each generation. The nature of the imprint must therefore be epigenetic (modifications to the structure of the chromatinChromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
rather than DNA sequence). In germline
Germline
In biology and genetics, the germline of a mature or developing individual is the line of germ cells that have genetic material that may be passed to a child.For example, gametes such as the sperm or the egg, are part of the germline...
cells the imprint is erased and then re-established according to the sex
Sex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
of the individual; i.e. in the developing sperm (during spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
), a paternal imprint is established, whereas in developing oocytes (oogenesis
Oogenesis
Oogenesis, ovogenesis or oögenesis is the creation of an ovum . It is the female form of gametogenesis. The male equivalent is spermatogenesis...
), a maternal imprint is established. This process of erasure and reprogramming
Reprogramming
Reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development. After fertilization some cells of the newly formed embryo migrate to the germinal ridge and will eventually become the germ cells...
is necessary such that the current imprinting status is relevant to the sex of the individual. In both plants and mammals there are two major mechanisms that are involved in establishing the imprint; these are DNA methylation
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
and histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
modifications.
Regulation
The grouping of imprinted genes within clusters allows them to share common regulatory elements, such as non-coding RNARNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
s and differentially methylated regions (DMRs). When these regulatory elements control the imprinting of one or more genes, they are known as imprinting control regions (ICR). The expression of non-coding RNA
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...
s, such as Air on mouse chromosome 17 and KCNQ1OT1
KCNQ1OT1
KCNQ1 overlapping transcript 1, also known as KCNQ1OT1, is a long non-coding RNA gene found in the KCNQ1 locus. This locus consists of 8-10 protein-coding genes, specifically expressed from the maternal allele , and the paternally expressed non-coding RNA gene KCNQ1OT1. KCNQ1OT1 is found as a 91...
on human chromosome 11p15.5, have been shown to be essential for the imprinting of genes in their corresponding regions.
Differentially methylated regions are generally segments of DNA rich in cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
and guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
nucleotides, with the cytosine nucleotides methylated on one copy but not on the other. Contrary to expectation, methylation does not necessarily mean silencing; instead, the effect of methylation depends upon the default state of the region.
Functions of imprinted genes
The control of expression of specific genes by genomic imprinting is unique to theriaTheria
Theria is a subclass of mammals that give birth to live young without using a shelled egg, including both eutherians and metatherians . The only omitted extant mammal group is the egg-laying monotremes....
n mammals (placental mammals and marsupials) and flowering plants. Imprinting of whole chromosomes has been reported in mealybugs (Genus: Pseudococcus
Pseudococcus
Pseudococcus is a genus of unarmoured scale insects in the family Pseudococcidae containing more than 150 species.-Species:Species include:*Pseudococcus aberrans*Pseudococcus acirculus*Pseudococcus affinis*Pseudococcus africanus...
). and a fungus gnat
Fungus gnat
Fungus gnats are small, dark, short-lived flies, of the families Sciaridae, Diadocidiidae, Ditomyiidae, Keroplatidae, Bolitophilidae and Mycetophilidae , sometimes placed in the superfamily Mycetophiloidea, whose larvae feed on plant roots or fungi and aid in the decomposition of organic matter...
(Sciara). It has also been established that X-chromosome inactivation occurs in an imprinted manner in the extra-embryonic tissues of mice and all tissues in marsupials, where it is always the paternal X-chromosome which is silenced.
The majority of imprinted genes in mammals have been found to have roles in the control of embryonic growth and development, including development of the placenta. Other imprinted genes are involved in post-natal development, with roles affecting suckling and metabolism.
Theories on the origins of imprinting
A widely accepted hypothesis for the evolution of genomic imprinting is the "parental conflict hypothesis."The kinship theory of genomic imprinting
The kinship theory of genomic imprinting is an evolutionary account of the origin and evolution of imprinted genes. When two alleles at a diploid locus differ in their optimal gene expression level depending on their parent of origin, the theory predicts the evolutionary outcome to be imprinted...
Also known as the kinship theory of genomic imprinting, this hypothesis states that the inequality between parental genomes due to imprinting is a result of the differing interests of each parent
Sexual conflict
Sexual conflict occurs when the two sexes have conflicting optimal fitness strategies concerning reproduction, particularly the mode and frequency of mating, leading to an evolutionary arms race between males and females. The conflict encompasses the actions and behaviors of both sexes to influence...
in terms of the evolutionary fitness of their genes
Fitness (biology)
Fitness is a central idea in evolutionary theory. It can be defined either with respect to a genotype or to a phenotype in a given environment...
. The father
Father
A father, Pop, Dad, or Papa, is defined as a male parent of any type of offspring. The adjective "paternal" refers to father, parallel to "maternal" for mother...
's genes that encode for imprinting gain greater fitness through the success of the offspring, at the expense of the mother
Mother
A mother, mum, mom, momma, or mama is a woman who has raised a child, given birth to a child, and/or supplied the ovum that grew into a child. Because of the complexity and differences of a mother's social, cultural, and religious definitions and roles, it is challenging to specify a universally...
. The mother's evolutionary imperative is often to conserve resources for her own survival while providing sufficient nourishment to current and subsequent litters. Accordingly, paternally expressed genes tend to be growth promoting whereas maternally expressed genes tend to be growth limiting. In support of this hypothesis, genomic imprinting has been found in all placental mammals, where post-fertilisation offspring resource consumption at the expense of the mother is high; although it has also been found in oviparous birds where there is relatively little post-fertilisation resource transfer and therefore less parental conflict.
However, our understanding of the molecular mechanisms behind genomic imprinting show that it is the maternal genome that controls much of the imprinting of both its own and the paternally-derived genes in the zygote, making it difficult to explain why the maternal genes would willingly relinquish their dominance to that of the paternally-derived genes in light of the conflict hypothesis. Several other hypotheses that propose a coadaptive reason for the evolution of genomic imprinting have been proposed.
Others have approached their study of the origins of genomic imprinting from a different side, arguing that natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
is operating on the role of epigenetic marks as machinery for homologous chromosome recognition during meiosis, rather than on their role in differential expression. This argument centers on the existence of epigenetic effects on chromosomes that do not directly affect gene expression, but do depend on which parent the chromosome originated from. This group of epigenetic changes that depend on the chromosome's parent of origin (including both those that affect gene expression and those that do not) are called parental origin effects, and include phenomena such as paternal X inactivation in the marsupials, nonrandom parental chromatid distribution in the ferns, and even mating type switching in yeast. This diversity in organisms that show parental origin effects has prompted theorists to place the evolutionary origin of genomic imprinting before the last common ancestor of plants and animals, over a billion years ago.
Natural selection for genomic imprinting requires genetic variation in a population. A hypothesis for the origin of this genetic variation states that the host-defense system responsible for silencing foreign DNA elements, such as genes of viral origin, mistakenly silenced genes whose silencing turned out to be beneficial for the organism. There appears to be an over-representation of retrotransposed
Transposon
Transposable elements are sequences of DNA that can move or transpose themselves to new positions within the genome of a single cell. The mechanism of transposition can be either "copy and paste" or "cut and paste". Transposition can create phenotypically significant mutations and alter the cell's...
genes, that is to say genes that are inserted into the genome by virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, among imprinted genes. It has also been postulated that if the retrotransposed gene is inserted close to another imprinted gene, it may just acquire this imprint.
Problems associated with imprinting
Imprinting may cause problems in cloningCloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...
, with clones having DNA that is not methylated
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
in the correct position. It is possible that this is due to a lack of time for reprogramming to be completely achieved. When a nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
is added to an egg during somatic cell nuclear transfer
Somatic cell nuclear transfer
In genetics and developmental biology, somatic-cell nuclear transfer is a laboratory technique for creating a clonal embryo, using an ovum with a donor nucleus . It can be used in embryonic stem cell research, or, potentially, in regenerative medicine where it is sometimes referred to as...
, the egg starts dividing in minutes, as compared to the days or months it takes for reprogramming during embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
nic development. If time is the responsible factor, it may be possible to delay cell division in clones, giving time for proper reprogramming to occur.
An allele of the "callipyge" (from the Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
for "beautiful buttocks"), or CLPG, gene in sheep produces large buttocks consisting of muscle with very little fat. The large-buttocked phenotype only occurs when the allele is present on the copy of chromosome 18 inherited from a sheep's father and is not on the copy of chromosome 18 inherited from that sheep's mother.
Prader-Willi/Angelman
The first imprinted genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s to be described in humans were the reciprocally inherited Prader-Willi syndrome
Prader-Willi syndrome
Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
and Angelman syndrome
Angelman syndrome
Angelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....
. Both syndromes are associated with loss of the chromosomal region 15q11-13 (band 11 of the long arm of chromosome 15). This region contains the paternally expressed genes (SNRPN and NDN
NDN (gene)
Necdin is a protein that in humans is encoded by the NDN gene.-Interactions:NDN has been shown to interact with NUCB2, E2F1, IL1A, Low affinity nerve growth factor receptor, P53 and HNRNPU.-Further reading:...
) and the maternally expressed gene (UBE3A
UBE3A
Ubiquitin-protein ligase E3A also known as E6AP ubiquitin-protein ligase is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells...
).
- Paternal inheritance of a deletion of this region is associated with Prader-Willi syndromePrader-Willi syndromePrader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
(characterised by hypotoniaHypotoniaHypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, obesityObesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, and hypogonadismHypogonadismHypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
). - Maternal inheritance of the same deletion is associated with Angelman syndromeAngelman syndromeAngelman syndrome is a neuro-genetic disorder characterized by intellectual and developmental delay, sleep disturbance, seizures, jerky movements , frequent laughter or smiling, and usually a happy demeanor....
(characterised by epilepsyEpilepsyEpilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, tremors, and a perpetually smiling facial expression).
NOEY2
NOEY2NOEY2
NOEY2 is a gene located on chromosome 1 in humans. It is maternally imprinted, and is linked to breast cancer....
is a paternally expressed imprinted gene located on chromosome 1 in humans. Loss of NOEY2 expression is linked to an increased risk of ovarian and breast cancers; in 41% of breast and ovarian cancers the protein transcribed by NOEY2 is not expressed, suggesting that it functions as a tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
Therefore, if a person inherits both chromosomes from the mother, the gene will not be expressed and the individual is put at a greater risk for breast and ovarian cancer.
Other
Other conditions involving imprinting include Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndrome
Beckwith–Wiedemann syndrome is an overgrowth disorder usually present at birth characterized by an increased risk of childhood cancer and certain congenital features. Originally, Dr...
, Silver-Russell syndrome, and pseudohypoparathyroidism
Pseudohypoparathyroidism
Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Patients have a low serum calcium and high phosphate, but the parathyroid hormone level is actually appropriately high...
.
Transient neonatal diabetes mellitus
Transient neonatal diabetes mellitus
Transient neonatal diabetes mellitus is a form of diabetes mellitus presenting at birth that is not permanent.Types include:It is to do with genetics and is often associated with having an added Chromosome 7 gene ....
can also involve imprinting.
The "imprinted brain theory
Imprinted brain theory
The imprinted brain theory is an evolutionary psychology theory regarding the causes of autism spectrum disorders and psychosis.- The conflict theory of imprinting :...
" argues that unbalanced imprinting may be a cause of autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
.
Imprinted genes in plants
A similar imprinting phenomenon has also been described in flowering plantFlowering plant
The flowering plants , also known as Angiospermae or Magnoliophyta, are the most diverse group of land plants. Angiosperms are seed-producing plants like the gymnosperms and can be distinguished from the gymnosperms by a series of synapomorphies...
s (angiosperms). During fertilisation of the egg cell, a second, separate fertilization event gives rise to the endosperm
Endosperm
Endosperm is the tissue produced inside the seeds of most flowering plants around the time of fertilization. It surrounds the embryo and provides nutrition in the form of starch, though it can also contain oils and protein. This makes endosperm an important source of nutrition in human diet...
, an extraembryonic structure that nourishes the embryo in a manner analogous to the mammalian placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
. Unlike the embryo, the endosperm is often formed from the fusion of two maternal cells with a male gamete
Gamete
A gamete is a cell that fuses with another cell during fertilization in organisms that reproduce sexually...
. This results in a triploid
Polyploidy
Polyploid is a term used to describe cells and organisms containing more than two paired sets of chromosomes. Most eukaryotic species are diploid, meaning they have two sets of chromosomes — one set inherited from each parent. However polyploidy is found in some organisms and is especially common...
genome. The uneven ratio of maternal to paternal genomes appears to be critical for seed development. Some genes are found to be expressed from both maternal genomes while others are expressed exclusively from the lone paternal copy.