Dominance relationship
Encyclopedia
Dominance in genetics
is a relationship between two variant forms (allele
s) of a single gene
, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms (A & B), three combinations of alleles (genotypes) are possible: AA, AB, and BB. If AA and BB individuals (homozygotes
) show different forms of the trait (phenotype
), and AB individuals (heterozygotes
) show the same phenotype as AA individuals, then allele A is said to dominate or be dominant to allele B, and B is said to be recessive to A. If instead AB has the same phenotype as BB, B is dominant to A.
s, and are described as diploid
. One chromosome of each pair is contributed by each parent: one by the female parent in her ovum
, and one by the male parent in his sperm
, which are joined at fertilization. The ovum and sperm cells have only one copy of each chromosome and are described as haploid
. Production of haploid gametes occurs through a process called meiosis
.
, singular locus). The genetic material in each chromosome comprises a series of discrete genes
that influence various traits. Thus, each gene also has a corresponding homologue, which may exist in different forms: the variant forms are called allele
s. The alleles at the same locus on the two homologous chromosomes may be identical or different.
In popular usage, "gene" and "allele" are often used interchangeably. This produces misunderstandings. Properly, "gene" refers to a hereditary unit, ordinarily at a fixed position on a chromosome, that influences a particular trait. Genes are now understood to comprise DNA
. "Allele" refers to any of the many particular forms of a gene that may be present in a population of individuals from a particular species, at a particular locus. E.g., it is inaccurate to say "This pea plant has a pair of wrinkled genes", and it is more accurate to say, "This plant has two 'w' alleles for the 'Seed Shape' gene, and will produce wrinkled peas." Consider also the example of blood type in humans. Near the long arm of chromosome nine appears a gene that determines whether an individual will be blood type, A, B, or O. 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.
. The genotype of an organism directly or indirectly affects its molecular, physical,and other traits, which individually or collectively are called the phenotype
. At heterozygous gene loci, the two alleles interact to produce the phenotype. The simplest form of allele interaction is the one described by Mendel, now called Mendelian, in which the appearance/phenotype caused by one allele is apparent, called dominant, and the appearance/phenotype caused by the other allele is not apparent, called recessive.
In the simplest case, the phenotypic effect of one allele completely masks the other in heterozygous combination; that is, the phenotype produced by the two alleles in heterozygous combination is identical to that produced by one of the two homozygous genotypes. The allele that masks the other is said to be dominant to the latter, and the alternative allele is said to be recessive to the former.
Dominance is a genotypic relationship between alleles, as manifested in the phenotype. It is unrelated to the nature of the phenotype itself, e.g., whether it is regarded as normal or abnormal, standard or nonstandard, healthy or diseased, stronger or weaker, or more or less extreme. It is also important to distinguish between the "round" gene locus, the "round" allele at that locus, and the "round" phenotype it produces. It is inaccurate to say that "the round gene dominates the wrinkled gene" or that "round peas dominate wrinkled peas."
Another system of notation designates the gene involved in seed shape as the "Shp" gene, which exists in two allelic forms, ShpR and Shpw, the dominance relationships of the two being indicated by the case of the superscripts. This system is the standard system in Drosophila
genetics.
, comprises three sets of alleles at the I locus, IA, IB, and IO. The first two are dominant to the latter: that is, the AA and AO genotypes produce indistinguishable blood group phenotypes, called "Type A", as do BB and BO, which produce "Type B" blood. In another example, coat color in siamese cats
and related breeds is determined by a series of alleles at the albino
gene locus (c) that produce different levels of pigment and hence different levels of color dilution. Four of these are c+, cb, cs, and ca (standard, Burmese
, siamese
, and albino
, respectively), where the first allele is completely dominant to the last three, and the last is completely recessive to the first three.
Co-dominance occurs when the contributions of both alleles are visible in the phenotype. In the ABO example, the IA and IB allele classes are co-dominant in producing the AB blood group phenotype, in which both A-type and B-type antigen
s are made. A third allele class, IO, produces no antigens and is recessive to both the others. Thus, a cross between an AO father and a BO mother produces four possible genotypes AO, AB, BO, and OO, corresponding to four phenotypes, A, AB, B, and O.
Another example occurs at the locus for the Beta-globin
component of hemoglobin
, 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 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 or semi-dominance, where the quantitative interaction of allele products produces an intermediate phenotype. For example, pink flowers might be the product of two co-dominant alleles that produce red and white pigments, which become mixed uniformly in the petals, or the result of one allele that produces the usual amount of red pigment and another non-functional allele that produces no pigment, so as to produce an intermediate amount of red pigment resulting in a diluted pink color.
species, sex is determined
by two sex chromosomes called the X chromosome
and the Y chromosome
. Human females are typically XX; males are typically XY. The remaining pairs of chromosome are found in both sexes and are called autosome
s; genetic traits due to 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 tend to be characteristic of one sex or the other. In practice, the term almost always refers to X-linked traits. 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 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, that allele is always expressed regardless of whether it is dominant or recessive. An example of sex-linked is: Hair loss is a trait caused by a gene located on the X chromosomes.
["epi + stasis = to sit on top"] is an interaction between genotypes at two different gene loci, which sometimes resembles a dominance interaction at a single locus. Epistasis modifies the characteristic 9:3:3:1 ratio expected for two non-epistatic genes. Most genetic systems involve complex epistatic interactions among multiple gene loci. 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 b allele is not dominant to the A allele: the B locus shows recessive epistasis to the A locus, 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 and 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 D- 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 produced only in C-D- genotypes, and not in any genotype combination with cc or dd. That is, both loci must have at least one dominant allele to produce the phenotype. This produces a characteristic ratio 9:7 ratio of pigmented to unpigmented plants.
or nucleotide
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
", 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 forms of the same protein (called isoform
s). Proteins often function as enzyme
s that catalyze chemical reactions in the cell, which directly or indirectly produce phenotypes. 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 (allozyme
s), it is likely that they produce the same phenotype with respect to enzyme action, and again neither allele can be said to be dominant.
Dominance typically occurs when one of the two alleles is non-functional at the molecular level, that is, it is not transcribed or else does not produce a protein product. This can be the result of a mutation
that alters the DNA sequence of the allele. An organism homozygous for the non-functional allele will generally show a distinctive phenotype, due to the absence of the protein product. For example, in humans and other organisms, the unpigmented skin of the albino
phenotype results when an individual is homozygous for an allele that prevents synthesis of the skin pigment protein melanin
. It is important to understand that it is not the lack of function that allows the allele to be described as recessive: this is the interaction with the alternative allele in the heterozygote. Three general types of interaction are possible:
In some cases, dominance of a non-standard allele results when that 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 variant alleles. This phenomenon occurs in a number of trinucleotide repeat diseases: for an example and more details see Huntington Disease.
(PKU) results from any of a large number (>60) of alleles at the gene locus for the enzyme phenylalanine hydroxylase
(PAH). Many of these alleles produce little or no PAH, as a result of which the substrate phenylalanine
and its metabolic byproducts accumulate in the central nervous system
and can cause severe mental retardation
if untreated.
The genotypes and phenotypic consequences of interactions among three 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 [phe] is about 60 uM. In untreated persons homozygous for one of the PKU alleles (BB), PAH activity is close to zero, [phe] ten to forty times standard, and the individual manifests PKU.
In the AB heterozygote, PAH activity is only 30% (not 50%) of standard, blood [phe] is 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 an incomplete dominant to B with respect to [phe], as 60 uM < 120 uM << 600 uM. Note once more that it is irrelevant to the question of dominance that the recessive allele produces a more extreme [phe] phenotype.
For a third allele C, a CC homozygote produces a very small amount of PAH enzyme, which results in a somewhat elevated level of [phe] in the blood, a condition called hyperphenylalanemia
, which does not result in mental retardation.
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.
, in the 1860s. Mendel observed that, for a variety of traits of garden peas having to do with the appearance of seeds, seed pods, and plant appearance, there occurred two discrete phenotypes: round vs wrinkled, or yellow vs green seeds, red vs white flowers, tall vs short plants, and so on. 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, and so on. However, when these hybrid plants were crossed, the offspring plants showed the two original phenotypes, in a characteristic 3:1 ratio, with the more common type having the phenotype of the parental hybrid plants. Mendel reasoned that each of the parents in the first cross were homozygotes for different alleles (AA and aa), that each contributed one allele to the offspring, such 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 three 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 afterward. He did introduce the notation of capital and lowercase letters for dominant and recessive alleles, respectively, still in use today.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
is a relationship between two variant forms (allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s) of a single gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms (A & B), three combinations of alleles (genotypes) are possible: AA, AB, and BB. If AA and BB individuals (homozygotes
Zygosity
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...
) show different forms of the trait (phenotype
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...
), and AB individuals (heterozygotes
Zygosity
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...
) show the same phenotype as AA individuals, then allele A is said to dominate or be dominant to allele B, and B is said to be recessive to A. If instead AB has the same phenotype as BB, B is dominant to A.
Diploid / haploid
Most familiar plants, like peas, and familiar animals, like fruit flies and humans, have paired chromosomeChromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s, and are described as diploid
Ploidy
Ploidy is the number of sets of chromosomes in a biological cell.Human sex cells have one complete set of chromosomes from the male or female parent. Sex cells, also called gametes, combine to produce somatic cells. Somatic cells, therefore, have twice as many chromosomes. The haploid number is...
. One chromosome of each pair is contributed by each parent: one by the female parent in her ovum
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
, and one by the male parent in his sperm
Sperm
The term sperm is derived from the Greek word sperma and refers to the male reproductive cells. In the types of sexual reproduction known as anisogamy and oogamy, there is a marked difference in the size of the gametes with the smaller one being termed the "male" or sperm cell...
, which are joined at fertilization. The ovum and sperm cells have only one copy of each chromosome and are described as haploid
Ploidy
Ploidy is the number of sets of chromosomes in a biological cell.Human sex cells have one complete set of chromosomes from the male or female parent. Sex cells, also called gametes, combine to produce somatic cells. Somatic cells, therefore, have twice as many chromosomes. The haploid number is...
. Production of haploid gametes occurs through a process called meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
.
Chromosomes, genes, and alleles
Each chromosome of a matching pair is structurally similar to the other, and each member of a homologous pair has the same genetic material arranged in the same order and physical locations (lociLocus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
, singular locus). The genetic material in each chromosome comprises a series of discrete genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
that influence various traits. Thus, each gene also has a corresponding homologue, which may exist in different forms: the variant forms are called allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s. The alleles at the same locus on the two homologous chromosomes may be identical or different.
In popular usage, "gene" and "allele" are often used interchangeably. This produces misunderstandings. Properly, "gene" refers to a hereditary unit, ordinarily at a fixed position on a chromosome, that influences a particular trait. Genes are now understood to comprise DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. "Allele" refers to any of the many particular forms of a gene that may be present in a population of individuals from a particular species, at a particular locus. E.g., it is inaccurate to say "This pea plant has a pair of wrinkled genes", and it is more accurate to say, "This plant has two 'w' alleles for the 'Seed Shape' gene, and will produce wrinkled peas." Consider also the example of blood type in humans. Near the long arm of chromosome nine appears a gene that determines whether an individual will be blood type, A, B, or O. 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.
Homozygous, heterozygous
If two alleles of a given gene are identical, the organism is called a homozygote and is 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 the genotypeGenotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
. The genotype of an organism directly or indirectly affects its molecular, physical,and other traits, which individually or collectively are called the phenotype
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...
. At heterozygous gene loci, the two alleles interact to produce the phenotype. The simplest form of allele interaction is the one described by Mendel, now called Mendelian, in which the appearance/phenotype caused by one allele is apparent, called dominant, and the appearance/phenotype caused by the other allele is not apparent, called recessive.
In the simplest case, the phenotypic effect of one allele completely masks the other in heterozygous combination; that is, the phenotype produced by the two alleles in heterozygous combination is identical to that produced by one of the two homozygous genotypes. The allele that masks the other is said to be dominant to the latter, and the alternative allele is said to be recessive to the former.
Which trait is dominant?
The terms dominant and recessive refer to the interaction of alleles in producing the phenotype of the heterozygote. If there are two alternative phenotypes, by definition the phenotype exhibited by the heterozygote is called "dominant" and the "hidden" phenotype is called "recessive". The key concept of dominance is that the heterozygote is phenotypically identical to one of the two homozygotes. That trait corresponding to the dominant allele may then be called the "dominant" trait.Dominance is a genotypic relationship between alleles, as manifested in the phenotype. It is unrelated to the nature of the phenotype itself, e.g., whether it is regarded as normal or abnormal, standard or nonstandard, healthy or diseased, stronger or weaker, or more or less extreme. It is also important to distinguish between the "round" gene locus, the "round" allele at that locus, and the "round" phenotype it produces. It is inaccurate to say that "the round gene dominates the wrinkled gene" or that "round peas dominate wrinkled peas."
Nomenclature
In genetics, the common convention is that dominant alleles are written as capital letters and recessive alleles as lower-case letters. In the pea example, once the dominance relationships of the two alleles are known, it is possible to designate the dominant allele that produces a round shape by a capital-letter symbol R, and the alternative 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. Note that the choice or "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.Another system of notation designates the gene involved in seed shape as the "Shp" gene, which exists in two allelic forms, ShpR and Shpw, the dominance relationships of the two being indicated by the case of the superscripts. This system is the standard system in Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
genetics.
Relationship to other genetic concepts
The concept of dominance is involved with a number of other genetic concepts.Multiple alleles
Although any individual has at most two different alleles, most genes exist in a large number of allelic forms in the population as a whole. In some cases, the alleles have different effects on the phenotype, and their dominance interactions with each other can be described as a series. For example, the best known human blood groups, the ABO systemABO blood group system
The ABO blood group system is the most important blood type system in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food,...
, comprises three sets of alleles at the I locus, IA, IB, and IO. The first two are dominant to the latter: that is, the AA and AO genotypes produce indistinguishable blood group phenotypes, called "Type A", as do BB and BO, which produce "Type B" blood. In another example, coat color in siamese cats
Siamese (cat)
The Siamese is one of the first distinctly recognized breeds of Oriental cat. The origins of the breed are unknown, but it is believed to be from Thailand. In Thailand, where they are one of several native breeds, they are called Wichian Mat...
and related breeds is determined by a series of alleles at the albino
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
gene locus (c) that produce different levels of pigment and hence different levels of color dilution. Four of these are c+, cb, cs, and ca (standard, Burmese
Burmese (cat)
The Burmese is a breed of domesticated cats split into two subgroups: the American Burmese and the British Burmese . Most modern Burmese are descendants of one female cat called Wong Mau, which was brought from Burma to America in 1930...
, siamese
Siamese (cat)
The Siamese is one of the first distinctly recognized breeds of Oriental cat. The origins of the breed are unknown, but it is believed to be from Thailand. In Thailand, where they are one of several native breeds, they are called Wichian Mat...
, and albino
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
, respectively), where the first allele is completely dominant to the last three, and the last is completely recessive to the first three.
Incomplete and semi-dominance
Complete dominance occurs when the phenotype of the heterozygote is completely indistinguishable from that of the dominant homozygote. This is frequently not the case. Incomplete dominance occurs when the phenotype of the heterozygous genotype is an intermediate of the phenotypes of the homozygous genotypes. For example, the snapdragon flower color is either homozygous for 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.Co-dominance
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s are made. A third allele class, IO, produces no antigens and is recessive to both the others. Thus, a cross between an AO father and a BO mother produces four possible genotypes AO, AB, BO, and OO, corresponding to four phenotypes, A, AB, B, and O.
Another example occurs at the locus for the Beta-globin
HBB
Beta globin Beta globin Beta globin (HBB, β-globinprotin that, along with alpha globin (HBA), makes up the most common form of hemoglobin in adult humans. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains.-Gene locus:...
component of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
, where the three molecular phenotypes of HbA/HbA, HbA/HbS, and HbS/HbS are all distinguishable by protein electrophoresis
Protein electrophoresis
Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel electrophoresis Protein electrophoresis is a method...
. (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
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
into RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
.
Co-dominance, where allelic products co-exist in the phenotype, is different from incomplete or semi-dominance, where the quantitative interaction of allele products produces an intermediate phenotype. For example, pink flowers might be the product of two co-dominant alleles that produce red and white pigments, which become mixed uniformly in the petals, or the result of one allele that produces the usual amount of red pigment and another non-functional allele that produces no pigment, so as to produce an intermediate amount of red pigment resulting in a diluted pink color.
Autosomal versus sex-linked dominance
In humans and other mammalMammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
species, sex is determined
Sex-determination system
A sex-determination system is a biological system that determines the development of sexual characteristics in an organism. Most sexual organisms have two sexes. In many cases, sex determination is genetic: males and females have different alleles or even different genes that specify their sexual...
by two sex chromosomes called the X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
and the Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
. Human females are typically XX; males are typically XY. The remaining pairs of chromosome are found in both sexes and are called autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
s; genetic traits due to 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
Sex linkage
Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...
, because they tend to be characteristic of one sex or the other. In practice, the term almost always refers to X-linked traits. 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
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...
for these genes. The Y chromosome is much smaller than the X, and contains a much smaller set of genes that influence 'maleness', such as the SRY gene for testis determining factor
Testis determining factor
Testis-determining factor is a general term for the gene that results in maleness in humans and some other species.Certain genes cause chemical reactions that result in the development of testes...
. Dominance rules for sex-linked gene loci are determined by their behavior in the female: because the male has only one allele, that allele is always expressed regardless of whether it is dominant or recessive. An example of sex-linked is: Hair loss is a trait caused by a gene located on the X chromosomes.
Epistasis
EpistasisEpistasis
In 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...
["epi + stasis = to sit on top"] is an interaction between genotypes at two different gene loci, which sometimes resembles a dominance interaction at a single locus. Epistasis modifies the characteristic 9:3:3:1 ratio expected for two non-epistatic genes. Most genetic systems involve complex epistatic interactions among multiple gene loci. 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 b allele is not dominant to the A allele: the B locus shows recessive epistasis to the A locus, 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 and 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 D- 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 produced only in C-D- genotypes, and not in any genotype combination with cc or dd. That is, both loci must have at least one dominant allele to produce the phenotype. This produces a characteristic ratio 9:7 ratio of pigmented to unpigmented plants.
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 basesBases
Bases may refer to:*Bases , a military style of dress adopted by the chivalry of the sixteenth century.*Business Association of Stanford Entrepreneurial Students...
or nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s of deoxyribonucleic acid
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
(DNA) at a particular point on a chromosome. The central dogma of molecular biology
Central dogma of molecular biology
The central dogma of molecular biology was first articulated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970:In other words, the process of producing proteins is irreversible: a protein cannot be used to create DNA....
states that "DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
makes RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
makes protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
", that is, that DNA is transcribed
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
to make an RNA copy, and RNA is translated
Translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. Whereas interpreting undoubtedly antedates writing, translation began only after the appearance of written literature; there exist partial translations of the Sumerian Epic of...
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 forms of the same protein (called isoform
Protein isoform
A protein isoform is any of several different forms of the same protein. Different forms of a protein may be produced from related genes, or may arise from the same gene by alternative splicing. A large number of isoforms are caused by single-nucleotide polymorphisms or SNPs, small genetic...
s). Proteins often function as 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...
s that catalyze chemical reactions in the cell, which directly or indirectly produce phenotypes. 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 (allozyme
Allozyme
Variant forms of an enzyme that are coded by different alleles at the same locus are called allozymes. These are opposed to isozymes, which are enzymes that perform the same function, but which are coded by genes located at different loci....
s), it is likely that they produce the same phenotype with respect to enzyme action, and again neither allele can be said to be dominant.
Dominance typically occurs when one of the two alleles is non-functional at the molecular level, that is, it is not transcribed or else does not produce a protein product. This can be the result of 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...
that alters the DNA sequence of the allele. An organism homozygous for the non-functional allele will generally show a distinctive phenotype, due to the absence of the protein product. For example, in humans and other organisms, the unpigmented skin of the albino
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
phenotype results when an individual is homozygous for an allele that prevents synthesis of the skin pigment protein melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
. It is important to understand that it is not the lack of function that allows the allele to be described as recessive: this is the interaction with the alternative allele in the heterozygote. Three general types of interaction are possible:
- In the typical case, the single functional allele makes sufficient protein to produce a phenotype identical to that of the homozygote: this is called haplosufficiency. 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.
- Alternatively, a single functional allele in the heterozygote may produce insufficient gene product for proper function, and the phenotype resembles that of the homozygote for the non-functional allele. This haploinsufficiencyHaploinsufficiencyHaploinsufficiency occurs when a diploid organism only has a single functional copy of a gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state...
is much less common: usually the deficiency of gene product results in incomplete dominance (below). - 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 (HBBHBBBeta globin Beta globin Beta globin (HBB, β-globinprotin that, along with alpha globin (HBA), makes up the most common form of hemoglobin in adult humans. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains.-Gene locus:...
) that is one of the two globinGlobinGlobins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
proteins that make up the blood pigment hemoglobinHemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
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 anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
called sickle-cell anemia. Persons heterozygous HbA/HbS for this allele have a much less severe form of anemia called sickle-cell trait. 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.
In some cases, dominance of a non-standard allele results when that 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 variant alleles. This phenomenon occurs in a number of trinucleotide repeat diseases: for an example and more details see Huntington Disease.
Dominant and recessive genetic diseases in humans
In humans, many genetic traits or diseases are classified simply as "dominant" or "recessive." Especially with respect to so-called recessive diseases, this can oversimplify the underlying molecular basis and lead to misunderstanding of the nature of dominance. For example, the genetic disease phenylketonuriaPhenylketonuria
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...
(PKU) results from any of a large number (>60) of alleles at the gene locus for the enzyme 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...
(PAH). Many of these alleles produce little or no PAH, as a result of which the substrate 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...
and its metabolic byproducts accumulate in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and can cause severe 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...
if untreated.
The genotypes and phenotypic consequences of interactions among three alleles are shown in the following table:
| Genotype | PAH activity | [phe] conc | PKU ? |
|---|---|---|---|
| AA | 100% | 60 uM | No |
| AB | 30% | 120 uM | No |
| CC | 5% | 200 ~ 300 uM | Hyperphenylalanemia |
| BB | 0.3% | 600 ~ 2400 uM | Yes |
In unaffected persons homozygous for a standard functional allele (AA), PAH activity is standard (100%), and the concentration of phenylalanine in the blood [phe] is about 60 uM. In untreated persons homozygous for one of the PKU alleles (BB), PAH activity is close to zero, [phe] ten to forty times standard, and the individual manifests PKU.
In the AB heterozygote, PAH activity is only 30% (not 50%) of standard, blood [phe] is 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 an incomplete dominant to B with respect to [phe], as 60 uM < 120 uM << 600 uM. Note once more that it is irrelevant to the question of dominance that the recessive allele produces a more extreme [phe] phenotype.
For a third allele C, a CC homozygote produces a very small amount of PAH enzyme, which results in a somewhat elevated level of [phe] in the blood, a condition called hyperphenylalanemia
Hyperphenylalanemia
Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated levels of the amino acid phenylalanine in the blood. Severe hyperphenylalaninemia results in phenylketonuria . Phenylalanine concentrations are routinely screened in newborns by the Guthrie test, which takes...
, which does not result in mental retardation.
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.
History
The concept of dominance was first described by the "Father of Genetics," Gregor MendelGregor 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...
, in the 1860s. Mendel observed that, for a variety of traits of garden peas having to do with the appearance of seeds, seed pods, and plant appearance, there occurred two discrete phenotypes: round vs wrinkled, or yellow vs green seeds, red vs white flowers, tall vs short plants, and so on. 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, and so on. However, when these hybrid plants were crossed, the offspring plants showed the two original phenotypes, in a characteristic 3:1 ratio, with the more common type having the phenotype of the parental hybrid plants. Mendel reasoned that each of the parents in the first cross were homozygotes for different alleles (AA and aa), that each contributed one allele to the offspring, such 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 three 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 afterward. He did introduce the notation of capital and lowercase letters for dominant and recessive alleles, respectively, still in use today.
See also
- Mitochondrial DNAMitochondrial DNAMitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
- Sex linkageSex linkageSex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...
- Evolution of dominanceEvolution of dominanceThe evolution of dominance concerns the evolution of genetic dominance. The central argument, that modifier genes act upon other genes to make them dominant or recessive, and that these are then themselves subject to natural selection was first proposed by the British population geneticist Ronald...
- List of Mendelian traits in humans
External links
- "Online Mendelian Inheritance in Man (OMIM)"
- "Autosomal dominance of Huntington's Disease". Huntington's Disease Outreach Project for Education at StanfordHuntington's Disease Outreach Project for Education at StanfordThe Huntington’s disease Outreach Project for Education at Stanford is a student-run project at Stanford University dedicated to making scientific information about Huntington’s disease more readily accessible to patients and the public. Initiated by Professor William H...