Pleiotropy
Encyclopedia
Pleiotropy occurs when one gene
influences multiple phenotypic
traits. Consequently, a mutation
in a pleiotropic gene may have an effect on some or all traits simultaneously. This can become a problem when selection
on one trait favors one specific version of the gene (allele
), while the selection on the other trait favors another allele.
πλείων pleion, meaning "more", and τροπή tropí, meaning "turn, convert". A common mistake is to use "pleiotrophic" instead of "pleiotropic".
written by the german geneticist Ludwig Plate, a former student of Ernst Haeckel
. The term "polyphaeon" was also suggested in 1925 by Haeckel but did not persist. Even before the term was proposed there were examples of distinct traits that seemed to be inherited together. In his classic 1866 paper, Gregor Mendel
listed his trait number three in peas as having brown seed coat, violet flowers, and axial spots.
A classic example of pleiotropy is the human disease PKU (phenylketonuria
). This disease can cause mental retardation
and reduced hair
and skin
pigment
ation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme
(phenylalanine hydroxylase
), which converts the amino acid
phenylalanine
to tyrosine
, another amino acid. Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body. PKU is totally benign if a diet free from phenylalanine is maintained.
refers to the expression
of a gene resulting in multiple competing effects, some beneficial but others detrimental to the organism.
This is central to a theory of aging first developed by G. C. Williams
in 1957. Williams suggested that some genes responsible for increased fitness in the younger, fertile organism contribute to decreased fitness later in life. An example is the p53
gene, which suppresses cancer, but also suppresses stem cell
s, which replenish worn-out tissue.
Whether or not pleiotropy is antagonistic may depend upon the environment; for instance, a bacterial gene that enhances glucose
utilization efficiency at the expense of the ability to use other energy sources (such as lactose) has positive effects when there is plenty of glucose, but can be lethal if lactose is the only available food source.
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...
influences multiple phenotypic
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
traits. Consequently, a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in a pleiotropic gene may have an effect on some or all traits simultaneously. This can become a problem when 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....
on one trait favors one specific version of the gene (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...
), while the selection on the other trait favors another allele.
Etymology
The term pleiotropy comes from the GreekGreek 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;...
πλείων pleion, meaning "more", and τροπή tropí, meaning "turn, convert". A common mistake is to use "pleiotrophic" instead of "pleiotropic".
History
The term "pleiotropie" was coined in a 1910 FestschriftFestschrift
In academia, a Festschrift , is a book honoring a respected person, especially an academic, and presented during his or her lifetime. The term, borrowed from German, could be translated as celebration publication or celebratory writing...
written by the german geneticist Ludwig Plate, a former student of Ernst Haeckel
Ernst Haeckel
The "European War" became known as "The Great War", and it was not until 1920, in the book "The First World War 1914-1918" by Charles à Court Repington, that the term "First World War" was used as the official name for the conflict.-Research:...
. The term "polyphaeon" was also suggested in 1925 by Haeckel but did not persist. Even before the term was proposed there were examples of distinct traits that seemed to be inherited together. In his classic 1866 paper, Gregor Mendel
Gregor Mendel
Gregor Johann Mendel was an Austrian scientist and Augustinian friar who gained posthumous fame as the founder of the new science of genetics. Mendel demonstrated that the inheritance of certain traits in pea plants follows particular patterns, now referred to as the laws of Mendelian inheritance...
listed his trait number three in peas as having brown seed coat, violet flowers, and axial spots.
Mechanism
Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets.A classic example of pleiotropy is the human disease PKU (phenylketonuria
Phenylketonuria
Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
). This disease can cause mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
and reduced hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
and skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
pigment
Pigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...
ation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
(phenylalanine hydroxylase
Phenylalanine hydroxylase
Phenylalanine hydroxylase is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PheOH is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for...
), which converts the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
to tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
, another amino acid. Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body. PKU is totally benign if a diet free from phenylalanine is maintained.
Antagonistic pleiotropy
Antagonistic pleiotropyAntagonistic pleiotropy hypothesis
The antagonistic pleiotropy hypothesis was first proposed by George C. Williams in 1957 as an explanation for senescence. Pleiotropy is the phenomenon where one gene controls for more than one phenotypic trait in an organism...
refers to the expression
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...
of a gene resulting in multiple competing effects, some beneficial but others detrimental to the organism.
This is central to a theory of aging first developed by G. C. Williams
George C. Williams
Professor George Christopher Williams was an American evolutionary biologist.Williams was a professor emeritus of biology at the State University of New York at Stony Brook. He was best known for his vigorous critique of group selection. The work of Williams in this area, along with W. D...
in 1957. Williams suggested that some genes responsible for increased fitness in the younger, fertile organism contribute to decreased fitness later in life. An example is the p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
gene, which suppresses cancer, but also suppresses stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s, which replenish worn-out tissue.
Whether or not pleiotropy is antagonistic may depend upon the environment; for instance, a bacterial gene that enhances glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
utilization efficiency at the expense of the ability to use other energy sources (such as lactose) has positive effects when there is plenty of glucose, but can be lethal if lactose is the only available food source.
Evolution
Pleiotropy of genes impacts the evolutionary rate of genes. Traditionally it has been expected that evolutionary rate of genes is related negatively with pleiotropy, however this has not been clearly found in empirical data . Contrary to this traditional expectation, it has been theoretically demonstrated that evolutionary rate should be positively related with pleiotropy by itself as the square root of gene pleiotropy , however other effects of pleiotropy may explain why a clear relationship between evolutionary rate and gene pleiotropy has not been found at genomic scale .See also
- EpistasisEpistasisIn genetics, epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are sometimes called modifier genes. The gene whose phenotype is expressed is called epistatic, while the phenotype altered or suppressed is called hypostatic...
- Metabolic networkMetabolic networkA metabolic network is the complete set of metabolic and physical processes that determine the physiological and biochemical properties of a cell...
- Metabolic supermiceMetabolic supermiceMetabolic supermice are mice which as a result of genetic modification have up to 100 times the concentration of the PEPCK-C enzyme in their muscles, compared to ordinary mice....
- Enhancer (genetics)Enhancer (genetics)In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...