Pleiotropy

Pleiotropy (from Ancient Greek πλείων (pleíōn) 'more' and τρόπος (trópos) 'turn, way, manner, style') is a condition in which a single gene or genetic variant influences multiple phenotypic traits. A gene that has such multiple effects is referred to as a pleiotropic gene. Mutations in pleiotropic genes can affect several traits simultaneously, often because the gene product is used in various cells and affects different biological targets through shared signaling pathways.

Pleiotropy can result from several distinct but potentially overlapping mechanisms, including gene pleiotropy, developmental pleiotropy, and selectional pleiotropy. Gene pleiotropy occurs when a gene product interacts with multiple proteins or catalyzes different reactions. Developmental pleiotropy refers to mutations that produce several phenotypic effects during development. Selectional pleiotropy occurs when a single phenotype influences evolutionary fitness in multiple ways (depending on factors such as age and sex).

There are also three main types of genetic pleiotropic effects when a variant or gene is associated with more than one trait:

A well-known example of pleiotropy is phenylketonuria (PKU), a genetic disorder caused by a mutation in a single gene on chromosome 12 that encodes the enzyme phenylalanine hydroxylase. This mutation leads to the accumulation of the amino acid phenylalanine in the body, affecting multiple systems, such as the nervous and integumentary system.

Pleiotropic gene action can limit the rate of multivariate evolution when natural selection, sexual selection or artificial selection on one trait favors one allele, while selection on other traits favors a different allele. Pleiotropic mutations can sometimes be deleterious, especially when they negatively affect essential traits. Genetic correlations and responses to selection most often exemplify pleiotropy.

Pleiotropy is widespread in the genome, with many genes influencing biological traits and pathways. Understanding pleiotropy is crucial in genome-wide association studies (GWAS), where variants are often linked to multiple traits or diseases.

Pleiotropic traits had been previously recognized in the scientific community but had not been experimented on until Gregor Mendel's 1866 pea plant experiment. Mendel recognized that certain pea plant traits (seed coat color, flower color, and axial spots) seemed to be inherited together; however, their correlation to a single gene has never been proven.

The term "pleiotropie" was first coined by Ludwig Plate in his Festschrift, which was published in 1910. He originally defined pleiotropy as occurring when "several characteristics are dependent upon ... [inheritance]; these characteristics will then always appear together and may thus appear correlated". This definition is still used today.