Complete dominance

SIGNIFICANCE: Complete dominance represents one of the classic Mendelian forms of inheritance. In an individual that is heterozygous for a trait, the allele that displays complete dominance will determine the phenotype of the individual. Knowing whether the pattern of expression of a trait is dominant or recessive helps in making predictions concerning the inheritance of a particular genetic condition or disorder in a family’s history.

The Discovery and Definition of Dominance

Early theories of inheritance were based on the idea that fluids carrying materials for the production of a new individual were transmitted to offspring from the parents. It was assumed that substances in these fluids from the two parents mixed and that the children would therefore show a blend of the parents’ characteristics. For instance, an individual with dark hair mated to an individual with very light hair would be expected to produce offspring with medium-colored hair. The carefully controlled breeding studies carried out in the 1700s and 1800s did not produce the expected blended phenotypes, but no other explanation was suggested until Gregor Mendel proposed his model of inheritance. In the 1860s, Mendel repeated studies using the garden pea and obtained the same results seen by other investigators, but he counted the numbers of each type produced from each mating and developed his theory based on those observations.

One of the first observations Mendel dealt with was the appearance of only one of the parental traits in the first generation of offspring (the first filial, or F₁, generation). For example, a cross of tall plants and dwarf plants resulted in offspring that were all tall. Mendel proposed that the character expression (in this case height) was controlled by a determining “factor,” later called the “gene.” He then proposed that there were different forms of this controlling factor corresponding to the different expressions of the characteristic and termed these “alleles.” In the case of plant height, one allele produced tall individuals and the other produced dwarf individuals. He further proposed that in the cross of a tall (D) plant and a dwarf (d) plant, each parent contributed one factor for height, so the offspring were Dd. (Uppercase letters denote dominant alleles, while lowercase letters denote recessive alleles.) These plants contained a factor for both the tall expression and the dwarf expression, but the plants were all tall, so “tall” was designated the dominant for the height trait.

Mendel recognized from his studies that the determining factors occurred in pairs—each sexually reproducing individual contains two alleles for each inherited characteristic. When he made his crosses, he carefully selected pure breeding parents that would have two copies of the same allele. In Mendel’s terminology, the parents would be homozygous: a pure tall parent would be designated DD, while a dwarf parent would be designated dd. His model also proposed that each parent would contribute one factor for each characteristic to each offspring, so the offspring of such a mating should be Dd (heterozygous). The tall appearance of the defines the character expression (the phenotype) as dominant. Dominance of expression for any characteristic cannot be guessed but must be determined by observation. When variation is observed in the phenotype, individuals must be examined to determine which expression is observed. For phenotypes that are not visible, such as blood types or enzyme-activity variations, a test of some kind must be used to determine which phenotype expression is present in any individual.

Mendel’s model and the appearance of the dominant phenotype also explain the classic 3:1 ratio observed in the second (F₂) generation. The crossing of two heterozygous individuals (Dd × Dd) produces a progeny that is ¼ DD, ½ Dd, and ¼ dd. Because there is a dominant phenotype expression, the ¼ DD and the ½ Dd progeny all have the same phenotype, so ¾ of the individuals are tall. It was this numerical relation that Mendel used to establish his model of inheritance.

The Functional Basis of Dominance

The development of knowledge about the molecular activity of genes through the 1950s and 1960s provided information on the nature of the synthesis of proteins using the genetic code passed on in the DNA molecules. This knowledge has allowed researchers to explain variations in phenotype expression and explain why a dominant allele behaves the way it does at the functional level. An enzyme’s function is determined by its structure, and that structure is coded for in the genetic information. The simplest situation is one in which the gene product is an enzyme that acts on a specific chemical reaction that results in a specific chemical product, the phenotype. If that enzyme is not present or if its structure is modified so that it cannot properly perform its function, then the chemical action will not be carried out. The result will be an absence of the normal product and a phenotype expression that varies from the normal expression. For example, melanin is a brown pigment produced by most animals. It is the product of a number of chemical reactions, but one enzyme early in the process is known to be defective in albino animals. Lacking normal enzyme activity, these animals cannot produce melanin, so there is no color in the skin, eyes, or hair. When an animal has the genetic composition cc (c designates colorless, or albino), it has two alleles that are the same, and neither can produce a copy of the normal enzyme. Animals with the genetic composition CC (C designates colored or normal) have two copies of the allele that produces normal enzymes and are therefore pigmented. When homozygous normal (CC) and albino (cc) animals are crossed, heterozygous (Cc) animals are produced. The c allele codes for production of an inactive enzyme, while the C allele codes for production of the normal, active enzyme. The presence of the normal enzyme promotes pigment production, and the animal displays the pigmented phenotype. The presence of pigment in the heterozygote leads to the designation that the pigmented phenotype is dominant to albinism or, conversely, that albinism is a recessive phenotype because it is seen only in the homozygous (cc) state.

The same absence or presence of an active copy of an enzyme explains why blood types A and B are both dominant to O. When an A allele or a B allele is present, an active enzyme promotes the production of a substance that is identified in a blood test; the blood type A expression or the blood type B expression is seen. When neither of these alleles is present, the individual is homozygous (OO). There is no detectable product present, and the blood test is negative; therefore, the individual has blood type O. When the A allele and the B allele are both present in a heterozygous individual, each produces an active enzyme, so both the A and the B product are detected in blood tests; such an individual has blood type AB. The two phenotypes are both expressed in the heterozygote, a mode of called codominance.

When there are multiple alleles present for the expression of a characteristic, a dominance relation among the phenotype expressions can be established. In some animal coats, very light colors result from enzymes produced by a specific allele that is capable of producing melanin but at a much less efficient rate than the normal version of the enzyme. In the rabbit, chinchilla (c^ch) is such an allele. In the Cch heterozygote, the normal allele (C) produces a normal, rapidly acting enzyme, and the animal has normal levels of melanin. The normal pigment phenotype expression is observed because the animals are dark in color, so this expression is dominant to the chinchilla phenotype expression. In the heterozygote c^chc, the slow-acting enzyme produced by the c^ch allele is present and produces pigment in a reduced amount, so the chinchilla phenotype expression is observed and is dominant to the albino phenotype expression. The result is a dominance hierarchy in which the normal pigment phenotype is dominant to both the chinchilla and the albino phenotypes, and the chinchilla expression is dominant to the albino expression.

It is important to note that the dominant phenotype is the result of the protein produced by each allele. In the previous examples, both the albino allele and the chinchilla allele produce a product—a version of the encoded enzyme—but the normal allele produces a version of the enzyme that produces more pigment. The relative ability of the enzymes to carry out the function determines the observed phenotype expression and therefore the dominance association. The C allele does not inhibit the activity of either of the other two alleles or their enzyme products, and the allele does not, therefore, show dominance; rather, its enzyme expression does.

Dominant Mutant Alleles

Dominance of a normal phenotype is fairly easy to explain at the level of the functioning protein because the action of the normal product is seen, but dominance of mutant phenotypes is more difficult. Polydactyly, the presence of extra fingers on one hand or extra toes on one foot, is a dominant phenotype. The mechanism that leads to this expression and numerous other developmental abnormalities is not yet understood.

One insight comes from the genetic expression of enzymes that are composed of two identical subunits. In this situation, the gene locus codes for one polypeptide, but it takes two polypeptide molecules joined together to form a functional enzyme molecule. In order to function normally, both of the polypeptide subunits must be normal. A heterozygote can have one allele coding for a normal polypeptide and the other allele coding for a mutant, nonfunctional polypeptide. These polypeptides will join together at random to form the enzyme. The possible combinations will be defective-defective, which results in a nonfunctional enzyme; defective-normal, which also results in a nonfunctional enzyme; and normal-normal, which is a normal, functional enzyme. The majority of the enzyme molecules will be nonfunctional, and their presence will interfere with the action of the few normal units. The normal function will be, at best, greatly reduced, and the overall phenotype will be abnormal. One form of hereditary blindness is dominant because the presence of abnormal proteins interferes with the transport of both protein types across a membrane to their proper location in the cells that react to light. The abnormal phenotype appears in the heterozygote, so the abnormal phenotype is dominant. A number of human disease conditions, including some forms of cancer, display a dominant mode of inheritance.

Sometimes a trait that appears to be dominant is actually more complex. The Manx trait in cats, which results in a very short, stubby tail, occurs only in heterozygous individuals. On the surface, this would appear to be a simple case of dominance, where the Manx allele, T, is dominant to the normal tail allele, t. Recall that when two heterozygotes are mated, the expected phenotype ratio in the offspring is 3:1, dominant:recessive. If two Manx cats are mated, the phenotype ratio in the offspring is 2:1, Manx:normal, because kittens that are homozygous for the Manx allele (TT) die very early in development and are reabsorbed by the mother cat. Therefore, the Manx allele does not display complete dominance but rather incomplete dominance. The Manx allele is lethal in the homozygous state and causes a short, stubby tail in the heterozygous state. This occurs because the Manx allele causes a developmental defect that affects spinal development. If one normal allele is present, the spine develops enough for the cat to survive, although it will display the Manx trait. In mutant homozygotes (TT), the spine is unable to develop, which proves lethal to the developing fetus.

Impact and Applications

One of the aims of human genetic research is to find cures for inherited conditions. When a condition shows the recessive phenotype expression, treatment may be effective. The individual lacks a normal gene product, so supplying that product can have a beneficial effect. This is the reason for the successful treatment of diabetes using insulin. There are many technical issues to be considered in such treatments, but current successes give hope for the treatment of other recessive genetic conditions.

Dominant disorders, on the other hand, will be much more difficult to treat. An affected heterozygous individual has a normal allele that produces normal gene product. The nature of the interactions between the products results in the defective phenotype. Supplying more normal product may not improve the situation. A great deal more knowledge about the nature of the underlying mechanisms will be needed to make treatment effective.

Key terms

• allelesdifferent forms of a gene at a specific locus; in most organisms, including humans, there are typically two alleles for each genetic trait
• genotypea description of the alleles at a gene locus
• heterozygotean individual with two different alleles at a gene locus
• homozygotean individual with two like alleles at a gene locus
• incomplete dominancethe expression of a trait that results when one allele can only partly dominate or mask the other
• locus: (pl.loci) the specific location of a particular gene on a chromosome
• phenotypethe observed expression of a genotype

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