Pleiotropic Effects: Definition and Examples

Pleiotropy refers to the phenomenon where a single gene has multiple effects on an organism’s phenotype or observable traits. It can affect the phenotypic behavior or characteristics in one or different ways.

A pleiotropic effect, thus, refers to the specific effect of a single gene on multiple areas, with mixed symptoms, or organ functions. For an instance, a gene that affects the color of the hair might also indirectly affect eye color or the pigmentation of the skin.

Good thing is, pleiotropic effects can also be beneficial if not mostly detrimental. It is observed in many different organisms like bacteria, plants, and animals.

Is the Pleiotropic effect applicable only in genetics?

While pleiotropy is a concept that is most commonly applied in genetics it can also denote broadly to other areas of biology.

A single molecule or protein could affect different cellular processes, or a single environmental factor could bring multiple changes in different plants or ecosystems. There are other examples in terms of human health where a single risk factor drags on different aspects of health. Also, a drug could have multiple side effects.

Thus the term “pleiotropy” might not remain such specific. It can be broadly applicable to a single factor influencing multiple systems.

Examples of pleiotropic effects

Sickle cell disease related pleiotropic effects

Possibly the oldest monogenic disease ever described in the literature. This is a genetic disease that affects the structure of red blood cells which become twisted into a crescent shape. It is how the disease gets its characteristic name.

In this disease, a single nucleotide substitution occurs in the HBB gene causing the production of hemoglobin S (with defective beta globin protein). If a single allele is mutated, half of the cells produced are sickle-shaped (referred to as sickle cell trait) and if both alleles are mutated all the cells are affected (referred to as sickle cell disease). The result is the malformed hemoglobin molecule with the characteristic “sickling of the red blood cell” that is unable to carry oxygen.

This can cause a variety of health problems, including anemia, organ damage, and pain crises with further complications.

However, due to this, the people who carry the sickle cell trait (meaning they have one copy of the sickle cell gene but not two) have a low risk of developing malaria. The reason is that the sickle-shaped red blood cells are less habitable by the malaria parasite (Plasmodium), reducing the likelihood of infection.

This is an example of a pleiotropic effect where a single gene mutation produces multiple effects.

Lactase persistence related pleiotropic effects

Another example of pleiotropic effect is lactase persistence. Lactase is an enzyme that breaks down lactose, which is he sugar found in milk.

In mammals including humans, lactase production decreases after weaning.

However, in many human populations, lactase production persists into adulthood. This allows individuals to continue digesting lactose.

The responsible gene, lactase persistence allele (LCT) is thought to have evolved in populations that relied heavily on dairy products for their nutrition. However, the allele has also been associated with increased risk of certain health conditions like osteoporosis and some types of cancer.

This is an example of pleiotropy because a single genetic mutation has both positive effects (allowing individuals to digest lactose and access an important source of nutrition) and also negative effects (increasing the risk of certain health conditions).

The BRCA1 Gene related pleiotropy

Mutations in BRCA1 gene are known to increase the risk of breast and ovarian cancers. However, they are also linked to other health conditions.

Studies have found that women with BRCA1 mutations may be at increased risk of developing osteoporosis heart disease compared to women without the mutation. There are also evidence that BRCA1 mutations may affect the immune system and increase the risk of autoimmune disorders.

This is also an example of pleiotropy because a single gene mutation has effects and association with multiple aspects of health.

The PCSK9 gene related pleiotropic effects

This gene is involved in regulating cholesterol levels in the blood. Mutations in PCSK9 can result in either abnormally high or low cholesterol levels.

 It is also found that individuals with specific PCSK9 mutations may also have a reduced risk of developing Alzheimer’s disease. The reason for this is thought to be related to the role of PCSK9 in clearing amyloid-beta (a protein that can accumulate in the brain) is associated with Alzheimer’s disease.

Here, a single gene has effects on both cholesterol regulation and the risk of Alzheimer’s disease – a perfect example of pleiotropic effects.

TP53 related pleiotropic effect

The TP53 gene is a tumor suppressor gene that plays a critical role in preventing the development of cancer. Mutations in TP53 have been linked to a wide range of cancers, including breast, colon, and lung cancer.

However, TP53 is also linked to other important roles in the body. It is involved in the regulation of the immune system and can play a role in the development of autoimmune disorders. Simultaneously, TP53 has been shown to be involved in the regulation of cell growth and the aging process.

Angiotensin Converting Enzyme (ACE) related pleiotropy

ACE codes for the angiotensin converting enzyme (ACE). The enzyme is involved in regulating blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor.

Variations in the ACE gene have been associated with increased risk for a variety of health conditions, including hypertension, myocardial infarction, and chronic kidney disease. On the other side, ACE gene is also linked to other health outcomes like endurance performance in athletes.

The common ACE gene variant called the “I allele” has been associated with better endurance performance in certain athletic activities like long-distance running.

The mechanism underlying this effect is not entirely clear, but it may involve differences in the ability of the ACE enzyme to break down other signaling molecules involved in muscle metabolism.

Pleiotropic effects of statins

Pleiotropic effects of statins
Pleiotropic effects of statins: Medcrave

Statins are a class of medications that are widely used to lower cholesterol levels in the blood. They work by inhibiting an enzyme called HMG-CoA reductase that is involved in the production of cholesterol in the liver.

By lowering cholesterol levels, statins can reduce the risk of heart disease, stroke, and other cardiovascular events.

In addition to their cholesterol-lowering effects, statins have been found to have a number of other beneficial effects on health.

Studies have suggested that statins may have anti-inflammatory and antioxidant properties –  they could help to reduce the risk of other diseases – cancer and Alzheimer’s disease.

Statins have also shown to improve endothelial function, which is the ability of blood vessels to dilate in response to changes in blood flow. This can help to reduce blood pressure and improve blood flow to the heart and other organs.

While statins are generally considered safe and effective, they can also cause side effects in some people. These including muscle pain, liver damage, and increased risk of diabetes.

For this reason, it is important to weigh the potential benefits and risks of statin use on a case-by-case basis taking into account the factors such as age, family history, and other health conditions.

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