Pleiotropy

 The term pleiotropy is derived from the Greek words pleio, which means "many," and tropic, which means "affecting." Genes that affect multiple, apparently unrelated, phenotypes are thus called pleiotropic genes.

Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. The underlying mechanism is genes that code for a product that is either used by various cells or has a cascade-like signaling function that affects various targets.

During his study of inheritance in pea plants, Gregor Mendel made several interesting observations regarding the color of various plant components. Specifically, Mendel noticed that plants with colored seed coats always had colored flowers and colored leaf axils.

Mendel also observed that pea plants with colorless seed coats always had white flowers and no pigmentation on their axils. In other words, in Mendel's pea plants, seed coat color was always associated with specific flower and axil colors. Today, we know that Mendel's observations were the result of pleiotropy or the phenomenon in which a single gene contributes to multiple phenotypic traits. In this case, the seed coat color gene was not only responsible for seed coat color, but also for flower and axil pigmentation.

A single gene might be involved in multiple pathways. For instance, consider the amino acid tyrosine. This substance is needed for general protein synthesis, and it is also a precursor for several neurotransmitters (e.g., dopamine, norepinephrine), the hormone thyroxine, and the pigment melanin. Thus, mutations in any one of the genes that affect tyrosine synthesis or metabolism may affect multiple body systems.

Examples of pleiotropy

Vestigial wings in the fruit fly

In the fruit fly Drosophila, the vestigial gene plays a critical role in wing development. In fact, if these flies are homozygous for the recessive form of the vestigial gene (vg), they will develop short wings, and they will be unable to fly as a direct result. Along with regulating wing development, the vg gene is also pleiotropic. Indirectly, the gene changes the number of egg strings in a fly's ovaries, alters the position of bristles on a fly's scutellum, and decreases the length of a fly's life.

Albinism

Albinism is the mutation of the TYR gene, also termed tyrosinase. This mutation causes the most common form of albinism. The mutation alters the production of melanin, thereby affecting melanin-related and other dependent traits throughout the organism. Melanin is a substance made by the body that is used to absorb light and provides coloration to the skin. Indications of albinism are the absence of color in an organism's eyes, hair, and skin, due to the lack of melanin. Some forms of albinism are also known to have symptoms that manifest themselves through rapid-eye movement, light sensitivity, and strabismus.

Phenylketonuria

A common example of pleiotropy is the human disease phenylketonuria (PKU). This disease causes mental retardation and reduced hair and skin pigmentation and can be caused by any of a large number of mutations in the single gene on chromosome 12 that codes for the enzyme phenylalanine hydroxylase, which converts the amino acid phenylalanine to tyrosine. Depending on the mutation involved, this conversion is reduced or ceases entirely. Unconverted phenylalanine builds up in the bloodstream and can lead to levels that are toxic to the developing nervous system of newborn and infant children. The most dangerous form of this is called classic PKU, which is common in infants. The baby seems normal at first but actually incurs permanent intellectual disability. This can cause symptoms such as mental retardation, abnormal gait and posture, and delayed growth. Because tyrosine is used by the body to make melanin (a component of the pigment found in the hair and skin), failure to convert normal levels of phenylalanine to tyrosine can lead to fair hair and skin.

Sickle cell anemia

Sickle cell anemia is a genetic disease that causes deformed red blood cells with a rigid, crescent shape instead of the normal flexible, round shape. It is caused by a change in one nucleotide, a point mutation in the HBB gene. The HBB gene encodes information to make the beta-globin subunit of hemoglobin, which is the protein red blood cells use to carry oxygen throughout the body. Sickle cell anemia is a pleiotropic disease because the expression of a single mutated HBB gene produces numerous consequences throughout the body. The mutated hemoglobin forms polymers and clumps together causing the deoxygenated sickle red blood cells to assume the disfigured sickle shapes result, the cells are inflexible and cannot easily flow through blood vessels, increasing the risk of blood clots and possibly depriving vital organs of oxygen. Some complications associated with sickle cell anaemia include pain, damaged organs, strokes, high blood pressure, and loss of vision. Sickle red blood cells also have a shortened lifespan and die prematurely.