recessive

In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect 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 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 (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see Sex linkage). Since there is only one copy of the Y chromosome, 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 and classical genetics. Letters and Punnett squares 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 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) individuals have round peas, and the ''rr'' (homozygous) individuals have wrinkled peas. In ''Rr'' (heterozygous) 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). 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. 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 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 proposed that dominance acted based on natural selection through the contribution of modifier genes. In 1929, American geneticist Sewall Wright 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 chromosomes, 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 gametes, described as haploid, and created through meiosis. These gametes then fuse during fertilization during sexual reproduction, into a new single cell zygote, 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 (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 alleles. 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 and is said to be homozygous with respect to that gene; if instead the two alleles are different, the organism is a heterozygote 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. 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) 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 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, 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, 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 (''I^A'', ''I^B'') and dominant over the recessive ''i'' at the ABO locus. The ''I^A'' and ''I^B'' alleles produce different modifications. The enzyme coded for by ''I^A'' adds an N-acetylgalactosamine to a membrane-bound H antigen. The ''I^B'' enzyme adds a galactose. The ''i'' allele produces no modification. Thus the ''I^A'' and ''I^B'' alleles are each dominant to ''i'' (''I^AI^A'' and ''I^Ai'' individuals both have type A blood, and ''I^BI^B'' and ''I^Bi'' individuals both have type B blood), but ''I^AI^B'' individuals have both modifications on their blood cells and thus have type AB blood, so the ''I^A'' and ''I^B'' alleles are said to be co-dominant.

Another example occurs at the locus for the beta-globin component of hemoglobin, where the three molecular phenotypes of ''Hb^A/Hb^A'', ''Hb^A/Hb^S'', and ''Hb^S/Hb^S'' are all distinguishable by protein electrophoresis. (The medical condition produced by the heterozygous genotype is called '' sickle-cell trait'' and is a milder condition distinguishable from '' sickle-cell anemia'', 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 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 disorders.

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'': ''A^y'', dominant yellow; ''a⁺'', wild type; and ''a^bt'', black and tan. The ''a^bt'' allele is recessive to the wild type allele, and the ''A^y'' allele is codominant to the wild type allele. The ''A^y'' allele is also codominant to the ''a^bt'' 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), 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). The alleles ''C'', ''c^b'', ''c^s'', and ''c^a'' (full colour, Burmese, Siamese, and albino, 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 ''c^a'' 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 and the Y chromosome. 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 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. 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), 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 phenotyp