Monoallelic gene expression (MAE) is the phenomenon of the

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

, when only one of the two

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

copies (

alleles An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

) is actively expressed ( transcribed), while the other is silent.

Diploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...

organisms bear two homologous copies of each

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

(one from each parent), a gene can be expressed from both chromosomes (biallelic expression) or from only one (monoallelic expression). MAE can be ''Random monoallelic expression (RME)'' or ''Constitutive monoallelic expression (constitutive)''. ''Constitutive monoallelic expression'' occurs from the same specific allele throughout the whole organism or tissue, as a result of genomic imprinting. RME is a broader class of monoallelic expression, which is defined by random allelic choice in

somatic cells A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...

, so that different cells of the

multi-cellular organism A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni ...

express different alleles. Monoallelicexpr

Constitutive monoallelic gene expression

Random monoallelic gene expression (RME)

X-chromosome inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...

(XCI), is the most striking and well-studied example of RME. XCI leads to the transcriptional silencing of one of the X chromosomes in female cells, which results in expression of the genes that located on the other, remaining active

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...

. XCI is critical for balanced gene expression in

female mammals Female (symbol: ♀) is the sex of an organism that produces the large non-motile ova (egg cells), the type of gamete (sex cell) that fuses with the male gamete during sexual reproduction. A female has larger gametes than a male. Females ...

. The allelic choice of XCI by individual cells takes place randomly in epiblasts of the preimplantation embryo, which leads to

mosaic A mosaic is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and were particularly pop ...

gene expression of the paternal and maternal X chromosome in female tissues. XCI is a chromosome-wide monoallelic expression, that includes expression of all genes that are located on X chromosome, in contrast to ''

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

RME (aRME)'' that relates to single genes that are interspersed over the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

. aRME's can be fixed or dynamic, depending whether or not the allele-specific expression is conserved in daughter cells after

mitotic In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

Types of aRME

Fixed aRME are established either by silencing of one allele that previously has been biallelically expressed, or by activation of a single allele from previously silent gene. Expression activation of the silent allele is coupled with a feedback mechanism that prevents expression of the second allele. Another scenario is also possible due to limited time-window of low-probability initiation, that could lead to high frequencies of cells with single-allele expression. It is estimated that 2-10% of all genes are fixed aRME. Studies of fixed aRME require either expansion of monoclonal cultures or lineage-traced in vivo or in vitro cells that are mitotically. Dynamic aRME occurs as a consequence of

stochastic Stochastic (, ) refers to the property of being well described by a random probability distribution. Although stochasticity and randomness are distinct in that the former refers to a modeling approach and the latter refers to phenomena themselv ...

allelic expression. Transcription happens in bursts, which results in

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

molecules being synthesized from each allele separately. So over time, both alleles have a probability to initiate transcription. Transcriptional bursts are allelically stochastic, and lead to either maternal or paternal allele being accumulated in the cell. The gene transcription burst

frequency Frequency is the number of occurrences of a repeating event per unit of time. It is also occasionally referred to as ''temporal frequency'' for clarity, and is distinct from ''angular frequency''. Frequency is measured in hertz (Hz) which is eq ...

and

intensity Intensity may refer to: In colloquial use *Strength (disambiguation) *Amplitude * Level (disambiguation) * Magnitude (disambiguation) In physical sciences Physics *Intensity (physics), power per unit area (W/m2) *Field strength of electric, ma ...

combined with RNA-degradation rate form the shape of RNA distribution at the moment of observation and thus whether the gene is bi- or monoallelic. Studies that distinguish fixed and dynamic aRME require single-cell analyses of clonally related cells.

Mechanisms of aRME

Allelic exclusion Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. This phenomenon is most notable for playing a role in the development of B lymphocytes, where allelic exclusion allows for each matur ...

is a process of gene expression when one allele is expressed and the other one kept silent. Two most studied cases of allelic exclusion are monoallelic expression of

immunoglobulins An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

in B and

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

and

olfactory receptors Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ri ...

in sensory neurons. Allelic exclusion is cell-type specific (as opposed to organism-wide XCI), which increases intercellular diversity, thus specificity towards certain

antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

odors An odor (American English) or odour (Commonwealth English; see spelling differences) is caused by one or more volatilized chemical compounds that are generally found in low concentrations that humans and animals can perceive via their sense ...

. Allele-biased expression is skewed expression level of one allele over the other, but both alleles are still expressed (in contrast to allelic exclusion). This phenomenon is often observed in cells of immune function

Methods of detection

Methods of MAE detection are based on the difference between alleles, which can be distinguished either by the sequence of expressed mRNA or protein structure. Methods of MAE detection can be divided into single gene or whole genome MAE analysis. Whole genome MAE analysis cannot be performed based on protein structure yet, so these are completely

NGS NGS may refer to: Places * NGSO (NGS orbit), non-geostationary orbit * Nagasaki Airport (IATA airport code: NGS) in Omura, Nagasaki, Japan Organisations * National Galleries of Scotland, representing the national art collection of Scotland * Na ...

based techniques. Single-gene analysis Genome-wide analysis

References

External links

* {{cite journal , last1=Singer-Sam , first1=Judith , year=2010 , title=Monoallelic Expression , journal=Nature Education , volume=3 , issue=3 , pages=1 , url=https://www.nature.com/scitable/topicpage/monoallelic-expression-8813275 Gene expression