WHAT IS PLEIOTROPY? (WITH EXAMPLES) - BIOLOGY - 2025

The pleiotropy is the genetic phenomenon in which the expression of a gene in an individual affects the phenotypic expression of other unrelated characters. Etymologically, pleiotropy means "more changes" or "many effects": that is, more effects than expected from the expression of a single gene. It is also known as polyphenia (many phenotypes), but it is a rarely used term.

One of the phenomena of inheritance that most confused geneticists during the infancy of this science was that of mutations that affected more than one character.

At first it was believed that each character was controlled by a single gene. Then we realized that the manifestation of a character could require the participation of more than one gene.

What is most surprising, however, is that a single gene can affect the manifestation of more than one heritable trait, which is essentially what defines pleiotropy.

In general, when pleiotropy is demonstrated it is more appropriate to say that the responsible gene has pleiotropic effects than that the gene is pleiotropic.

Although not all adhere to this convention, it is important to note that the pleiotropic gene encodes a particular trait and not pleiotropy per se.

Otherwise, "normality" would be nothing more than the pleiotropic manifestation of the action of a wild allele of a particular gene on others. However, this is genetically wrong.

History

The term pleiotropy was first used by a German geneticist named Ludwig Plate in 1910. Plate used the term to explain the appearance of several different phenotypic traits that always occur together and can appear to be correlated. According to him, this phenomenon, when it occurs, is due to a unit of pleiotropic inheritance.

Another German, Hans Gruneberg, divided pleiotropy into "genuine" and "spurious." The first was characterized by the emergence of two distinct primary products from a single location.

The second, according to this author, referred to a single primary product that was used in different ways. Today the Gruneberg meaning of genuine pleiotropy has been discarded, while spurious pleiotropy is regarded simply as pleiotropy.

Another division of the pleiotropy concept was made by Ernst Hadorn, who pointed out that there were two types of pleiotropy: mosaic and relational. The first occurs when a gene encodes information that affects two different phenotypic traits.

Relational pleiotropy, on the other hand, occurs when a gene determines the initiation of different events related to each other and that will affect multiple independent traits.

Kacser and Burns, for their part, pointed out that any variation in any part of the genome affects all traits to different degrees, either directly or indirectly. This idea is known by the name of universal pleiotropy.

Examples of genes with pleiotropic effects

Pleiotropy, being a phenomenon that describes some of the consequences of the interaction between the products of genes, is universal.

Viruses, as well as all organisms of a cellular nature, possess genes whose products are important for the manifestation of other characters. These genes, whose wild-type and mutant alleles have pleiotropic effects, are of a different nature.

-The vestigial gene in Drosophila

In Drosophila (the fruit fly), the vestigial gene determines the level of development of the wings. When this gene is inherited from both parents, the descendant fly will present vestigial wings and will not be able to fly.

However, these will not be the only effects of the vestigial gene. This gene is pleiotropic and its presence also leads to a reduction in the number of eggs in the fly's ovaries. It also modifies the number and arrangement of the bristles in the thorax and reduces the life span is this.

-Pigmentation and deafness in cats

The gene that encodes pigmentation information in cats is a pleiotropic gene. Due to this, a fairly high percentage of cats with white fur and blue eyes are also deaf.

Even white cats that have a blue eye and a yellow eye are deaf only in the ear that is on the same side of the head as the blue eye.

Pleiotropy in cats. White cat with heterochromia. Taken and edited from: Keith Kissel, via Wikimedia Commons.

-Chicks with curled feathers

In chickens, a dominant gene produces the effect of ruffled feathers. This gene was shown to have a pleiotropic effect as it manifests other phenotypic effects: increased metabolic rates, increased body temperature, greater food consumption.

Additionally, chickens with this gene show delayed sexual maturity and decreased fertility.

-In humans

Marfan syndrome

Symptoms of this syndrome include: unusually tall body size, progressive heart disorders, dislocation of the lens of the eye, pulmonary disorders.

All of these symptoms are directly related to a single gene mutation. This gene, called FBN1, is pleiotropic, since its function is to encode a glycoprotein that is used in connective tissues in different parts of the body.

Holt-Oram syndrome

Patients with this syndrome have abnormalities in the carpal bones and other bones of the forelimbs. Additionally, about 3 out of 4 patients with this syndrome have heart problems.

Nijmegen syndrome

It is characterized by the fact that those who suffer from it have microcephaly, immunodeficiency, developmental disorders and a propensity for lymphatic cancer and leukemia.

-Phenylketonuria

A well-known case of pleiotropic effect is caused by mutant alleles responsible for phenylketonuria.

Phenylketonuria, a metabolic disease, is due to the mutation of a single gene that codes for the enzyme phenylalanine hydroxylase. The inactive mutant enzyme is unable to break down the amino acid phenylalanine; when this accumulates, the organism becomes intoxicated.

Therefore, the effect observed in individuals carrying the two copies of the mutated gene is multiple (pleiotropic).

The cause of the disease, or syndrome, is the lack of metabolic activity that causes skin eruptions, neurological disorders, microcephaly, fair skin and blue eyes (due to the lack of melanin generation), etc., through different routes.

None of the genes involved in the altered manifestation of these other traits is necessarily mutated.

-Other metabolic pathways

It is very common the case in which several enzymes share or use the same cofactor to be active. This cofactor is the end product of the concerted action of several other proteins that participate in this biosynthetic pathway.

If a mutation is generated in any of the genes that codes for the proteins of this pathway, the cofactor will not be produced. These mutations will have a pleiotropic effect, since none of the proteins that depend on the cofactor to be active will be able to be active, although their own genes are perfectly functional.

Molybdenum

In both prokaryotes and eukaryotes, for example, molybdenum is essential for the functioning of certain enzymes.

Molybdenum, to be biologically useful, must be complexed with another organic molecule, the product of the action of various enzymes in a complex metabolic pathway.

Once this cofactor complexed with molybdenum is formed, it will be used by all the molybdoproteins to each exercise its own function.

The pleiotropic effect in a mutation that prevents the synthesis of molybdocofactor will be manifested not only in the absence of it, but also in the loss of the enzymatic activity of all molybdoenzymes of the individual carrying the mutation.

-Laminopathies

The nuclear lamina is an intricate mesh inside the nucleus, dynamically attached to its inner membrane. The nuclear lamina regulates the architecture of the nucleus, the partition between euchromatin and heterochromatin, gene expression, as well as DNA replication, among other things.

The core lamina is made up of few proteins collectively known as laminins. As these are structural proteins that a multitude of many others interact with, any mutation that affects your genes will have pleiotropic effects.

The pleiotropic effects of mutations in laminin genes will manifest as diseases that are called laminopathies.

That is, a laminopathy is the pleiotropic manifestation resulting from mutations in laminin genes. The clinical manifestations of laminopathies include, but are not limited to, Progeria, Emery-Dreifuss muscular dystrophy, and a host of other conditions.

-Transcriptional regulators

Other genes whose mutations give rise to a multitude of different pleiotropic effects are those that code for transcriptional regulators.

These are proteins that specifically control gene expression; there are others that are general regulators of transcription. In any case, the absence of these products determines that other genes are not transcribed (that is, not expressed).

A mutation that determines the absence or malfunction of a general or specific transcriptional regulator will have pleiotropic effects in the organism, since no gene under its control will be expressed.

Pleiotropy and epigenetics

The discovery of mechanisms of alteration in gene expression that do not depend on changes in the nucleotide sequence of genes (epigenetics) has enriched our vision of pleiotropy.

One of the most studied aspects of epigenetics is the action of endogenous microRNAs. These are the product of the transcription of genes called mir.

The transcription of a mir gene gives rise to an RNA that, after being processed, acts in the cytoplasm as a small inactivating RNA.

These RNAs are called small silencing RNAs because they have the ability to be complementary to target messenger RNAs. By joining them, the messenger is degraded and the character is not expressed.

In some cases this small molecule can bind to more than one different messenger, giving rise, of course, to a pleiotropic effect.

Pleiotropy and aging

The explanation for the natural causes of senescence could lie in the effect of pleiotropic genes. According to a hypothesis put forward by GC Williams, senescence is the consequence of what he called antagonistic pleiotropy.

If there are genes whose products have antagonistic effects at different stages in an organism's life, then these genes could contribute to aging.

If the beneficial effects manifest before reproduction and the harmful effects after it, then they would be favored by natural selection. But otherwise, natural selection would work against those genes.

In this way, if the genes are really pleiotropic, senescence would be inevitable, since natural selection would always act in favor of genes that favor reproduction.

Pleiotropy and speciation

Sympatric speciation is a type of speciation that occurs without geographic barriers between populations. This type of speciation is apparently favored by pleiotropic mutations.

Mathematical simulation models developed by Kondrashov show that reproductive isolation between sympatric populations can occur due to the appearance of ecologically important quantitative traits under disruptive selection.

These same models indicate that these traits must be related to pleiotropic genes. If the changes are due to several genes, and not a pleiotropic one, recombination of genes during reproduction would prevent speciation. Pleiotropy would avoid the disruptive effects of recombination.

Pleiotropy and adaptation

The land is constantly changing. Organisms must constantly change to adapt to new conditions. These changes lead to what is known as evolution.

Many authors argue that evolution leads to an increasing complexity of organisms. This complexity can be morphological, where a particular character could evolve independently of another under specific environmental conditions.

However, as organisms become more complex, their ability to respond to changes slows down. This is what is called the “evolutionary cost of complexity”.

Mathematical models argue that adaptations due to changes in pleiotropic genes would be evolutionarily less costly than those due to changes in characters encoded by individual genes.

References

1. Brooker, RJ (2017). Genetics: Analysis and Principles. McGraw-Hill Higher Education, New York, NY, USA.
2. Goodenough, UW (1984) Genetics. WB Saunders Co. Ltd, Pkiladelphia, PA, USA.
3. Griffiths, AJF, Wessler, R., Carroll, SB, Doebley, J. (2015). An Introduction to Genetic Analysis (11 ^th ed.). New York: WH Freeman, New York, NY, USA.
4. Ho, R., Hegele, RA (2018) Complex effects of laminopathy mutations on nuclear structure and function. Clinical Genetics, doi: 10.1111 / cge.13455.
5. Lobo, I. (2008). Pleiotropy: one gene can affect multiple traits. Nature Education, 1:10.
6. Stitzer, MC, Ross-Ibarra, J. (2018) Maize domestication and gene interaction. The New Phytologist, 220: 395-408.