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genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, dominance is the phenomenon of one variant (
allele 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 ...
) of a
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 b ...
on a
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 ...
masking or overriding the
effect Effect may refer to: * A result or change of something ** List of effects ** Cause and effect, an idiom describing causality Pharmacy and pharmacology * Drug effect, a change resulting from the administration of a drug ** Therapeutic effect, a ...
of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...
in one of the genes, either new (''de novo'') or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes ( autosomes) and their associated traits, while those on
sex chromosomes A sex chromosome (also referred to as an allosome, heterotypical chromosome, gonosome, heterochromosome, or idiochromosome) is a chromosome that differs from an ordinary autosome in form, size, and behavior. The human sex chromosomes, a typical ...
(allosomes) are termed
X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type ...
,
X-linked recessive X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y ...
or
Y-linked Y linkage, also known as holandric inheritance (from Ancient Greek ὅλος ''hólos'', "whole" + ἀνδρός ''andrós'', "male"), describes traits that are produced by genes located on the Y chromosome. It is a form of sex linkage. Y&nbs ...
; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see
Sex linkage Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...
). Since there is only one copy of the
Y chromosome The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits. Dominance is a key concept in
Mendelian inheritance Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later popularize ...
and
classical genetics Classical genetics is the branch of genetics based solely on visible results of reproductive acts. It is the oldest discipline in the field of genetics, going back to the experiments on Mendelian inheritance by Gregor Mendel who made it possible ...
. Letters and
Punnett squares The Punnett square is a square diagram that is used to predict the genotypes of a particular cross or breeding experiment. It is named after Reginald C. Punnett, who devised the approach in 1905. The diagram is used by biologists to determine ...
are used to demonstrate the principles of dominance in teaching, and the use of upper case letters for dominant alleles and lower case letters for recessive alleles is a widely followed convention. A classic example of dominance is the inheritance of
seed A seed is an embryonic plant enclosed in a protective outer covering, along with a food reserve. The formation of the seed is a part of the process of reproduction in seed plants, the spermatophytes, including the gymnosperm and angiospe ...
shape in peas. Peas may be round, associated with allele ''R'', or wrinkled, associated with allele ''r''. In this case, three combinations of alleles (genotypes) are possible: ''RR'', ''Rr'', and ''rr''. The ''RR'' (
homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
) individuals have round peas, and the ''rr'' (homozygous) individuals have wrinkled peas. In ''Rr'' (
heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
) individuals, the ''R'' allele masks the presence of the ''r'' allele, so these individuals also have round peas. Thus, allele ''R'' is dominant over allele ''r'', and allele ''r'' is recessive to allele ''R''. Dominance is not inherent to an allele or its traits (
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
). It is a strictly relative effect between two alleles of a given gene of any function; one allele can be dominant over a second allele of the same gene, recessive to a third and co-dominant with a fourth. Additionally, one allele may be dominant for one trait but not others. Dominance differs from epistasis, the phenomenon of an allele of one gene masking the effect of alleles of a ''different'' gene.


Background

The concept of dominance was introduced by
Gregor Johann Mendel Gregor Johann Mendel, OSA (; cs, Řehoř Jan Mendel; 20 July 1822 – 6 January 1884) was a biologist, meteorologist, mathematician, Augustinian friar and abbot of St. Thomas' Abbey in Brünn (''Brno''), Margraviate of Moravia. Mendel was ...
. Though Mendel, "The Father of Genetics", first used the term in the 1860s, it was not widely known until the early twentieth century. Mendel observed that, for a variety of traits of garden peas having to do with the appearance of seeds, seed pods, and plants, there were two discrete phenotypes, such as round versus wrinkled seeds, yellow versus green seeds, red versus white flowers or tall versus short plants. When bred separately, the plants always produced the same phenotypes, generation after generation. However, when lines with different phenotypes were crossed (interbred), one and only one of the parental phenotypes showed up in the offspring (green, or round, or red, or tall). However, when these
hybrid Hybrid may refer to: Science * Hybrid (biology), an offspring resulting from cross-breeding ** Hybrid grape, grape varieties produced by cross-breeding two ''Vitis'' species ** Hybridity, the property of a hybrid plant which is a union of two dif ...
plants were crossed, the offspring plants showed the two original phenotypes, in a characteristic 3:1 ratio, the more common phenotype being that of the parental hybrid plants. Mendel reasoned that each parent in the first cross was a homozygote for different alleles (one parent AA and the other parent aa), that each contributed one allele to the offspring, with the result that all of these hybrids were heterozygotes (Aa), and that one of the two alleles in the hybrid cross dominated expression of the other: A masked a. The final cross between two heterozygotes (Aa X Aa) would produce AA, Aa, and aa offspring in a 1:2:1 genotype ratio with the first two classes showing the (A) phenotype, and the last showing the (a) phenotype, thereby producing the 3:1 phenotype ratio. Mendel did not use the terms gene, allele, phenotype, genotype, homozygote, and heterozygote, all of which were introduced later. He did introduce the notation of capital and lowercase letters for dominant and recessive alleles, respectively, still in use today. In 1928, British population geneticist
Ronald Fisher Sir Ronald Aylmer Fisher (17 February 1890 – 29 July 1962) was a British polymath who was active as a mathematician, statistician, biologist, geneticist, and academic. For his work in statistics, he has been described as "a genius who ...
proposed that dominance acted based on natural selection through the contribution of
modifier genes Epistasis is a phenomenon in genetics in which the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes, respectively termed modifier genes. In other words, the effect of the mutation is dep ...
. In 1929, American geneticist
Sewall Wright Sewall Green Wright FRS(For) Honorary FRSE (December 21, 1889March 3, 1988) was an American geneticist known for his influential work on evolutionary theory and also for his work on path analysis. He was a founder of population genetics alongsi ...
responded by stating that dominance is simply a physiological consequence of metabolic pathways and the relative necessity of the gene involved. Wright's explanation became a fact in genetics, and the debate was largely ended. Some traits may have their dominance influenced by evolutionary mechanisms, however.


Chromosomes, genes, and alleles

Most animals and some plants have paired
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 ...
s, and are described as diploid. They have two versions of each chromosome, one contributed by the mother's ovum, and the other by the father's sperm, known as
gamete A gamete (; , ultimately ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. In species that produce ...
s, described as haploid, and created through
meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...
. These gametes then fuse during
fertilization Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Proce ...
during
sexual reproduction Sexual reproduction is a type of reproduction that involves a complex life cycle in which a gamete ( haploid reproductive cells, such as a sperm or egg cell) with a single set of chromosomes combines with another gamete to produce a zygote th ...
, into a new single cell
zygote A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicell ...
, which divides multiple times, resulting in a new organism with the same number of pairs of chromosomes in each (non-gamete) cell as its parents. In mammalian genetics, autosomal dominant disorders have pedigrees that demonstrate a vertical pattern of inheritance. Each chromosome of a matching (homologous) pair is structurally similar to the other, and has a very similar DNA
sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...
( loci, singular locus). The DNA in each chromosome functions as a series of discrete genes that influence various traits. Thus, each gene also has a corresponding homologue, which may exist in different versions called
allele 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 ...
s. The alleles at the same locus on the two homologous chromosomes may be identical or different. For example, the blood type of humans is determined by the ABO gene which encodes variants of an enzyme that creates the A, B, AB, or O blood type located on the long or q arm of chromosome nine (9q34.2). There are three different alleles that could be present at this locus, but only two can be present in any individual, one inherited from their mother and one from their father. If two alleles of a given gene are identical, the organism is called a
homozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
and is said to be homozygous with respect to that gene; if instead the two alleles are different, the organism is a
heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
and is heterozygous. The genetic makeup of an organism, either at a single locus or over all its genes collectively, is called its genotype. The genotype of an organism, directly and indirectly, affects its molecular, physical, and other traits, which individually or collectively are called its
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
. At heterozygous gene loci, the two alleles interact to produce the phenotype.


Types of Dominance


Complete dominance

In complete dominance, the effect of one allele in a heterozygous genotype completely masks the effect of the other. The allele that masks is considered ''dominant'' to the other allele, and the masked allele is considered ''recessive''. Complete dominance in a heterozygote's phenotype is indistinguishable from a dominant homozygote's phenotype. A classic example of complete dominance is the inheritance of seed shape (pea shape) in peas. Peas may be round (associated with allele ''R'') or wrinkled (associated with allele ''r''). In this case, three combinations of alleles (
genotypes The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
) are possible: ''RR, rr, Rr.'' ''RR'' and ''rr'' are homozygous, and ''Rr'' is heterozygous. The ''RR'' individuals have round peas and the ''rr'' individuals have wrinkled peas. In ''Rr'' individuals, the ''R'' allele masks the presence of the ''r'' allele, so these individuals also have round peas. Thus, allele ''R'' is completely dominant to allele ''r'', and allele ''r'' is recessive to allele ''R''.


Incomplete dominance

Incomplete dominance (also called ''partial dominance'', ''semi-dominance'' or ''intermediate inheritance'') occurs when the phenotype of the heterozygous genotype is distinct from and often intermediate to the phenotypes of the homozygous genotypes. The phenotypic result often appears as a blended form of characteristics in heterozygous state. For example, the
snapdragon ''Antirrhinum'' is a genus of plants commonly known as dragon flowers, snapdragons and dog flower because of the flowers' fancied resemblance to the face of a dragon that opens and closes its mouth when laterally squeezed. They are native to r ...
flower color is homozygous for either red or white. When the red homozygous flower is paired with the white homozygous flower, the result yields a pink snapdragon flower. The pink snapdragon is the result of incomplete dominance. A similar type of incomplete dominance is found in the four o'clock plant wherein pink color is produced when true-bred parents of white and red flowers are crossed. In
quantitative genetics Quantitative genetics deals with phenotypes that vary continuously (such as height or mass)—as opposed to discretely identifiable phenotypes and gene-products (such as eye-colour, or the presence of a particular biochemical). Both branches u ...
, where phenotypes are measured and treated numerically, if a heterozygote's phenotype is exactly between (numerically) that of the two homozygotes, the phenotype is said to exhibit ''no dominance'' at all, i.e. dominance exists only when the heterozygote's phenotype measure lies closer to one homozygote than the other. When plants of the F1 generation are self-pollinated, the phenotypic and genotypic ratio of the F2 generation will be 1:2:1 (Red:Pink:White). See partial dominance hypothesis.


Co-dominance

Co-dominance occurs when the contributions of both alleles are visible in the phenotype and neither allele masks another. For example, in the
ABO blood group system The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 43 different blood type (or group) classification system ...
, chemical modifications to a glycoprotein (the H antigen) on the surfaces of blood cells are controlled by three alleles, two of which are co-dominant to each other (''IA'', ''IB'') and dominant over the recessive ''i'' at the ABO locus. The ''IA'' and ''IB'' alleles produce different modifications. The enzyme coded for by ''IA'' adds an N-acetylgalactosamine to a membrane-bound H antigen. The ''IB'' enzyme adds a galactose. The ''i'' allele produces no modification. Thus the ''IA'' and ''IB'' alleles are each dominant to ''i'' (''IAIA'' and ''IAi'' individuals both have type A blood, and ''IBIB'' and ''IBi'' individuals both have type B blood), but ''IAIB'' individuals have both modifications on their blood cells and thus have type AB blood, so the ''IA'' and ''IB'' alleles are said to be co-dominant. Another example occurs at the locus for the beta-globin component of
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
, where the three molecular phenotypes of ''HbA/HbA'', ''HbA/HbS'', and ''HbS/HbS'' are all distinguishable by protein electrophoresis. (The medical condition produced by the heterozygous genotype is called ''
sickle-cell trait Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that all ...
'' and is a milder condition distinguishable from ''
sickle-cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
'', thus the alleles show ''incomplete dominance'' with respect to anemia, see above). For most gene loci at the molecular level, both alleles are expressed co-dominantly, because both are transcribed into RNA. Co-dominance, where allelic products co-exist in the phenotype, is different from incomplete dominance, where the quantitative interaction of allele products produces an intermediate phenotype. For example, in co-dominance, a red homozygous flower and a white homozygous flower will produce offspring that have red and white spots. When plants of the F1 generation are self-pollinated, the phenotypic and genotypic ratio of the F2 generation will be 1:2:1 (Red:Spotted:White). These ratios are the same as those for incomplete dominance. Again, this classical terminology is inappropriate – in reality such cases should not be said to exhibit dominance at all.


Addressing common misconceptions

Dominance relates to the relationship between two versions of a gene. A dominant trait is usually in correspondence to inheritance patterns that can be seen in Punnett Squares. If an individual has two versions of a gene, then the gene that is frequently observed in further generations is considered "dominant". In genetics, there are a few misconceptions that are fairly common. It is thought that a dominant trait is "stronger" and "overpowers" a recessive trait. Dominant traits are also assumed more likely to be inherited as well as more prevalent in a population. The idea of dominant traits being male or masculine is another common misconception. The emergence of these different ideas is due to the various concepts of dominance in non-genetic settings; such as being strong, powerful and controlling; which differs from the genetic concept of dominance. Dominance does not determine whether an allele is deleterious, neutral, or advantageous. However,
selection Selection may refer to: Science * Selection (biology), also called natural selection, selection in evolution ** Sex selection, in genetics ** Mate selection, in mating ** Sexual selection in humans, in human sexuality ** Human mating strateg ...
must operate on genes indirectly through phenotypes and dominance affects the exposure of alleles in phenotypes, hence the rate of change in allele frequencies under selection. Deleterious recessive alleles may persist in a population at low frequencies, with most copies carried in heterozygotes, at no cost to those individuals. These rare recessives are the basis for many hereditary
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s.


Nomenclature

In genetics, symbols began as algebraic placeholders. When one allele is dominant to another, the oldest convention is to symbolize the dominant allele with a capital letter. The recessive allele is assigned the same letter in lower case. In the pea example, once the dominance relationship between the two alleles is known, it is possible to designate the dominant allele that produces a round shape by a capital-letter symbol R, and the recessive allele that produces a wrinkled shape by a lower-case symbol r. The homozygous dominant, heterozygous, and homozygous recessive genotypes are then written RR, Rr, and rr, respectively. It would also be possible to designate the two alleles as W and w, and the three genotypes WW, Ww, and ww, the first two of which produced round peas and the third wrinkled peas. The choice of "R" or "W" as the symbol for the dominant allele does not pre-judge whether the allele causing the "round" or "wrinkled" phenotype when homozygous is the dominant one. A gene may have several alleles. Each allele is symbolized by the locus symbol followed by a unique superscript. In many species, the most common allele in the wild population is designated the wild type allele. It is symbolized with a + character as a superscript. Other alleles are dominant or recessive to the wild type allele. For recessive alleles, the locus symbol is in lower case letters. For alleles with any degree of dominance to the wild type allele, the first letter of the locus symbol is in upper case. For example, here are some of the alleles at the ''a'' locus of the laboratory mouse, ''Mus musculus'': ''Ay'', dominant yellow; ''a+'', wild type; and ''abt'', black and tan. The ''abt'' allele is recessive to the wild type allele, and the ''Ay'' allele is codominant to the wild type allele. The ''Ay'' allele is also codominant to the ''abt'' allele, but showing that relationship is beyond the limits of the rules for mouse genetic nomenclature. Rules of genetic nomenclature have evolved as genetics has become more complex. Committees have standardized the rules for some species, but not for all. Rules for one species may differ somewhat from the rules for a different species.


Relationship to other genetic concepts


Multiple alleles

Although any individual of a diploid organism has at most two different alleles at any one locus (barring
aneuploidies Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...
), most genes exist in a large number of allelic versions in the population as a whole. If the alleles have different effects on the phenotype, sometimes their dominance relationships can be described as a series. For example, coat color in domestic cats is affected by a series of alleles of the ''TYR'' gene (which encodes the enzyme
tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxy ...
). The alleles ''C'', ''cb'', ''cs'', and ''ca'' (full colour, Burmese, Siamese, and
albino Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...
, respectively) produce different levels of pigment and hence different levels of colour dilution. The ''C'' allele (full colour) is completely dominant over the last three and the ''ca'' allele (albino) is completely recessive to the first three.


Autosomal ''versus'' sex-linked dominance

In humans and other mammal species, sex is determined by two sex chromosomes called the
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 ...
and the
Y chromosome The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...
. Human females are XX; males are XY. The remaining pairs of chromosome are found in both sexes and are called autosomes; genetic traits associated with loci on these chromosomes are described as autosomal, and may be dominant or recessive. Genetic traits on the X and Y chromosomes are called sex-linked, because they are linked to sex chromosomes, not because they are characteristic of one sex or the other. In practice, the term almost always refers to X-linked traits and a great many such traits (such as red-green colour vision deficiency) are not affected by sex. Females have two copies of every gene locus found on the X chromosome, just as for the autosomes, and the same dominance relationships apply. Males, however, have only one copy of each X chromosome gene locus, and are described as
hemizygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
for these genes. The Y chromosome is much smaller than the X, and contains a much smaller set of genes, including, but not limited to, those that influence 'maleness', such as the SRY gene for
testis determining factor Sex-determining region Y protein (SRY), or Testis-determining factor (TDF), is a DNA-binding protein (also known as gene-regulatory protein/transcription factor) encoded by the ''SRY'' gene that is responsible for the initiation of male sex d ...
. Dominance rules for sex-linked gene loci are determined by their behavior in the female: because the male has only one allele (except in the case of certain types of Y chromosome
aneuploidy Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...
), that allele is always expressed regardless of whether it is dominant or recessive. Birds have opposite sex chromosomes: male birds have ZZ and female birds ZW chromosomes. However, inheritance of traits reminds XY-system otherwise; male zebra finches may carry white colouring gene in their one of two Z chromosome, but females develop white colouring always. Grasshoppers have XO-system. Females have XX, but males only X. There is no Y chromosome at all.


Epistasis

Epistasis ''epi'' + ''stasis'' = to sit on top"is an interaction between alleles at two ''different'' gene loci that affect a single trait, which may sometimes resemble a dominance interaction between two ''different'' alleles at the ''same'' locus. Epistasis modifies the characteristic 9:3:3:1 ratio expected for two non-epistatic genes. For two loci, 14 classes of epistatic interactions are recognized. As an example of ''recessive epistasis'', one gene locus may determine whether a flower pigment is yellow (AA or Aa) or green (aa), while another locus determines whether the pigment is produced (BB or Bb) or not (bb). In a bb plant, the flowers will be white, irrespective of the genotype of the other locus as AA, Aa, or aa. The bb combination is ''not'' dominant to the A allele: rather, the B gene shows ''recessive epistasis'' to the A gene, because the B locus when homozygous for the ''recessive'' allele (bb) suppresses phenotypic expression of the A locus. In a cross between two AaBb plants, this produces a characteristic 9:3:4 ratio, in this case of yellow : green : white flowers. In ''dominant epistasis'', one gene locus may determine yellow or green pigment as in the previous example: AA and Aa are yellow, and aa are green. A second locus determines whether a pigment precursor is produced (dd) or not (DD or Dd). Here, in a DD or Dd plant, the flowers will be colorless irrespective of the genotype at the ''A'' locus, because of the epistatic effect of the dominant D allele. Thus, in a cross between two AaDd plants, 3/4 of the plants will be colorless, and the yellow and green phenotypes are expressed only in dd plants. This produces a characteristic 12:3:1 ratio of white : yellow : green plants. ''Supplementary epistasis'' occurs when two loci affect the same phenotype. For example, if pigment color is produced by CC or Cc but not cc, and by DD or Dd but not dd, then pigment is not produced in any genotypic combination with either cc ''or'' dd. That is, ''both'' loci must have at least one dominant allele to produce the phenotype. This produces a characteristic 9:7 ratio of pigmented to unpigmented plants. ''Complementary epistasis'' in contrast produces an unpigmented plant if and only if the genotype is cc ''and'' dd, and the characteristic ratio is 15:1 between pigmented and unpigmented plants. Classical genetics considered epistatic interactions between two genes at a time. It is now evident from molecular genetics that all gene loci are involved in complex interactions with many other genes (e.g., metabolic pathways may involve scores of genes), and that this creates epistatic interactions that are much more complex than the classic two-locus models.


Hardy–Weinberg principle (estimation of carrier frequency)

The frequency of the heterozygous state (which is the carrier state for a recessive trait) can be estimated using the Hardy–Weinberg formula: p^2+2pq+q^2=1 This formula applies to a gene with exactly two alleles and relates the frequencies of those alleles in a large population to the frequencies of their three genotypes in that population. For example, if ''p'' is the frequency of allele A, and ''q'' is the frequency of allele a then the terms ''p''2, 2''pq'', and ''q''2 are the frequencies of the genotypes AA, Aa and aa respectively. Since the gene has only two alleles, all alleles must be either A or a and . Now, if A is completely dominant to a then the frequency of the carrier genotype Aa cannot be directly observed (since it has the same traits as the homozygous genotype AA), however it can be estimated from the frequency of the recessive trait in the population, since this is the same as that of the homozygous genotype aa. i.e. the individual allele frequencies can be estimated: , , and from those the frequency of the carrier genotype can be derived: . This formula relies on a number of assumptions and an accurate estimate of the frequency of the recessive trait. In general, any real-world situation will deviate from these assumptions to some degree, introducing corresponding inaccuracies into the estimate. If the recessive trait is rare, then it will be hard to estimate its frequency accurately, as a very large sample size will be needed.


Dominant versus advantageous

The property of "dominant" is sometimes confused with the concept of advantageous and the property of "recessive" is sometimes confused with the concept of deleterious, but the phenomena are distinct. Dominance describes the phenotype of heterozygotes with regard to the phenotypes of the homozygotes and without respect to the degree to which different phenotypes may be beneficial or deleterious. Since many genetic disease alleles are recessive and because the word dominance has a positive connotation, the assumption that the dominant phenotype is superior with respect to fitness is often made. This is not assured however; as discussed below while most genetic disease alleles are deleterious and recessive, not all genetic diseases are recessive. Nevertheless, this confusion has been pervasive throughout the history of genetics and persists to this day. Addressing this confusion was one of the prime motivations for the publication of the
Hardy–Weinberg principle In population genetics, the Hardy–Weinberg principle, also known as the Hardy–Weinberg equilibrium, model, theorem, or law, states that allele and genotype frequencies in a population will remain constant from generation to generation in t ...
.


Molecular mechanisms

The molecular basis of dominance was unknown to Mendel. It is now understood that a gene locus includes a long series (hundreds to thousands) of bases or
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
s of deoxyribonucleic acid (DNA) at a particular point on a chromosome. The central dogma of molecular biology states that "'' DNA makes RNA makes
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
''", that is, that DNA is transcribed to make an RNA copy, and RNA is translated to make a protein. In this process, different alleles at a locus may or may not be transcribed, and if transcribed may be translated to slightly different versions of the same protein (called
isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...
s). Proteins often function as
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s that catalyze chemical reactions in the cell, which directly or indirectly produce phenotypes. Mutations within the genome can alter catalytic activity, and therefore affect dominance. In any diploid organism, the DNA sequences of the two alleles present at any gene locus may be identical (homozygous) or different (heterozygous). Even if the gene locus is heterozygous at the level of the DNA sequence, the proteins made by each allele may be identical. In the absence of any difference between the protein products, neither allele can be said to be dominant (see ''co-dominance'', above). Even if the two protein products are slightly different ( allozymes), it is likely that they produce the same phenotype with respect to enzyme action, and again neither allele can be said to be dominant.


Zygosity

Historically, Mendel's
Law of Independent Assortment Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later populariz ...
assumed that alleles will sort independently, with one allele being "dominant".
Zygosity Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...
, degree of similarity of an organism's alleles, may affect dominance. Within a diploid organism, these would be defined by the Haplotype interactions of the alleles. Gene haploidy may result in a single, functional allele making sufficient protein to produce a phenotype identical to that of the homozygote. Three general types of haplotype interactions are possible: # Haplosufficiency. In a diploid, a functional allele of a haplosufficient gene would be considered dominant, while a non-functional allele would be considered recessive. For example, suppose the standard amount of enzyme produced in the functional homozygote is 100%, with the two functional alleles contributing 50% each. The single functional allele in the heterozygote produces 50% of the standard amount of enzyme, which is sufficient to produce the standard phenotype. If the heterozygote and the functional-allele homozygote have identical phenotypes, the functional allele is dominant to the non-functional allele. This occurs at the albino gene locus: the heterozygote produces sufficient enzyme to convert the pigment precursor to melanin, and the individual has standard pigmentation. For example, in humans and other organisms, the unpigmented skin of the
albino Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...
phenotype results when an individual is homozygous for an allele that encodes a non-functional version of an enzyme needed to produce the skin pigment
melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
. # Incomplete Haploinsufficiency. Less commonly, the presence of a single functional allele gives a phenotype that is not normal, but less severe, than that of the non-functional homozygote. This occurs when the functional allele is not haplo-sufficient thus the terms haplo-insufficiency and incomplete dominance are typically applied to these cases. The intermediate interaction occurs where the heterozygous genotype produces a phenotype intermediate between the two homozygotes. Depending on which of the two homozygotes the heterozygote most resembles, one allele is said to show ''incomplete dominance'' over the other. For example, in humans the ''Hb'' gene locus is responsible for the Beta-chain protein ( HBB) that is one of the two
globin The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myogl ...
proteins that make up the blood pigment
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
. Many people are homozygous for an allele called ''HbA''; some persons carry an alternative allele called ''HbS'', either as homozygotes or heterozygotes. The hemoglobin molecules of ''HbS''/''HbS'' homozygotes undergo a change in shape that distorts the morphology of the red blood cells, and causes a severe, life-threatening form of
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
called
sickle-cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
. Persons heterozygous ''HbA''/''HbS'' for this allele have a much less severe form of anemia called
sickle-cell trait Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that all ...
. Because the disease phenotype of ''HbA''/''HbS'' heterozygotes is more similar to but not identical to the ''HbA''/''HbA'' homozygote, the ''HbA'' allele is said to be ''incompletely dominant'' to the ''HbS'' allele. # Complete Haploinsufficiency. A single functional allele in the heterozygote may produce insufficient gene product for any function of the gene, causing the usually non-functional alleles to become dominant. The phenotype will then resemble that of a homozygote with non-functional allele instead of the wild type. The non-functional allele would be said to be dominant to the wild-type phenotype's functional allele. This situation may occur when the non-functional allele produces a defective protein that interferes with the proper function of the protein produced by the standard allele. The presence of the defective protein "dominates" the standard protein, and the disease phenotype of the heterozygote more closely resembles that of the homozygote for two defective alleles. The term "dominant" is often incorrectly applied to defective alleles whose homozygous phenotype has not been examined, but which cause a distinct phenotype when heterozygous with the normal allele. This phenomenon occurs in a number of trinucleotide repeat diseases, one example being
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...
. In Huntington's Disease, complete haploinsufficiency causes the dominant effect of the mutant protein. Normally, a person has about 20 C-A-G nucleotide repeats in their HTT gene, but those with Huntington Disease have 40+ C-A-G repeats. Another example is Marfan syndrome, an inherited connective tissue disorder, caused by a mutation in the fibrillin-1 (FBN1) gene. One normal copy of the FBN1 gene is inherited from one parent while a dominant abnormal FBN1 gene copy in inherited by another parent.


Dominant-negative mutations

Many proteins are normally active in the form of a multimer, an aggregate of multiple copies of the same protein, otherwise known as a homomultimeric protein or homooligomeric protein. In fact, a majority of the 83,000 different enzymes from 9800 different organisms in the BRENDA Enzyme Database represent homooligomers. When the wild-type version of the protein is present along with a mutant version, a mixed multimer can be formed. A mutation that leads to a mutant protein that disrupts the activity of the wild-type protein in the multimer is a dominant-negative mutation. A dominant-negative mutation may arise in a human somatic cell and provide a proliferative advantage to the mutant cell, leading to its clonal expansion. For instance, a dominant-negative mutation in a gene necessary for the normal process of programmed cell death ( Apoptosis) in response to DNA damage can make the cell resistant to apoptosis. This will allow proliferation of the clone even when excessive DNA damage is present. Such dominant-negative mutations occur in the tumor suppressor gene ''
p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
''. The P53 wild-type protein is normally present as a four-protein multimer (oligotetramer). Dominant-negative ''p53'' mutations occur in a number of different types of cancer and pre-cancerous lesions (e.g. brain tumors, breast cancer, oral pre-cancerous lesions and oral cancer). Dominant-negative mutations also occur in other tumor suppressor genes. For instance two dominant-negative germ line mutations were identified in the Ataxia telangiectasia mutated (ATM) gene which increases susceptibility to breast cancer. Dominant negative mutations of the transcription factor C/EBPα can cause acute myeloid leukemia. Inherited dominant negative mutations can also increase the risk of diseases other than cancer. Dominant-negative mutations in
Peroxisome proliferator-activated receptor gamma Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a tran ...
(PPARγ) are associated with severe insulin resistance, diabetes mellitus and hypertension. Dominant-negative mutations have also been described in organisms other than humans. In fact, the first study reporting a mutant protein inhibiting the normal function of a wild-type protein in a mixed multimer was with the bacteriophage T4 tail fiber protein GP37. Mutations that produce a truncated protein rather than a full-length mutant protein seem to have the strongest dominant-negative effect in the studies of P53, ATM, C/EBPα, and bacteriophage T4 GP37. File:Autosomal recessive inheritance for affected enzyme.png, Hereditary defects in enzymes are generally inherited in an autosomal fashion because there are more non-X chromosomes than X-chromosomes, and a recessive fashion because the enzymes from the unaffected genes are generally sufficient to prevent symptoms in carriers. Exceptions include cases of
haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...
, where the unaffected gene cannot compensate for the affected one. Autosomal dominant inheritance for structural protein.png, On the other hand, hereditary defects in structural proteins (such as
osteogenesis imperfecta Osteogenesis imperfecta (; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that break easily. The range of symptoms—on the skeleton as well as on the body's other organs—may b ...
,
Marfan's syndrome Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have exceptionally flexible joints a ...
and Ehlers–Danlos syndromes) are generally autosomal dominant, because it is enough that some components are defective to make the whole structure dysfunctional. This is a dominant-negative process, wherein a mutated gene product adversely affects the non-mutated gene product within the same cell.


Dominant and recessive genetic diseases in humans

In humans, many genetic traits or diseases are classified simply as "dominant" or "recessive". Especially with so-called recessive diseases, which are indeed a factor of recessive genes, but can oversimplify the underlying molecular basis and lead to misunderstanding of the nature of dominance. For example, the recessive genetic disease
phenylketonuria Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also re ...
(PKU) results from any of a large number (>60) of alleles at the gene locus for the enzyme
phenylalanine hydroxylase Phenylalanine hydroxylase. (PAH) () is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class ...
(PAH). Many of these alleles produce little or no PAH, as a result of which the substrate phenylalanine (Phe) and its metabolic byproducts accumulate in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
and can cause severe
intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...
if untreated. To illustrate these nuances, the genotypes and phenotypic consequences of interactions among three hypothetical PAH alleles are shown in the following table: In unaffected persons homozygous for a standard functional allele (AA), PAH activity is standard (100%), and the concentration of phenylalanine in the blood ''Pheis about 60 μM (= μmol/L). In untreated persons homozygous for one of the PKU alleles (BB), PAH activity is close to zero, heten to forty times standard, and the individual manifests PKU. In the AB heterozygote, PAH activity is only 30% (not 50%) of standard, blood ''Pheis elevated two-fold, and the person does not manifest PKU. Thus, the A allele is dominant to the B allele with respect to PKU, but the B allele is incompletely dominant to the A allele with respect to its molecular effect, determination of PAH activity level (0.3% < 30% << 100%). Finally, the A allele is incompletely dominant to the B allele with respect to he as 60 μM < 120 μM << 600 μM. Note once more that it is irrelevant to the question of dominance that the recessive allele produces a more extreme hephenotype. For a third allele C, a CC homozygote produces a very small amount of PAH enzyme, which results in a somewhat elevated level of ''Phein the blood, a condition called
hyperphenylalaninemia Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations ( ...
, which does not result in intellectual disability. That is, the dominance relationships of any two alleles may vary according to which aspect of the phenotype is under consideration. It is typically more useful to talk about the phenotypic consequences of the allelic interactions involved in any genotype, rather than to try to force them into dominant and recessive categories.


See also

* Ambidirectional dominance *
List of Mendelian traits in humans Mendelian traits in humans are human traits that are substantially influenced by Mendelian inheritance. Most — if not all — Mendelian triaits are also influenced by other genes, the environment, immune responses, and chance. Therefore no ...
* Mitochondrial DNA * Punnett square


References


"On-line notes for Biology 2250 – Principles of Genetics"
Memorial University of Newfoundland. * — Sickle-Cell Anemia * — ABO blood groups


External links


"Online Mendelian Inheritance in Man"
(OMIM)

Huntington's Disease Outreach Project for Education at Stanford {{DEFAULTSORT:Dominance (Genetics) Classical genetics Genetics concepts * Quantitative genetics