Pleiotropy

This article is about genetic pleiotropy. For drug pleiotropy, see Pleiotropy (drugs).

Pleiotropy occurs when one gene influences multiple phenotypic traits. Consequently, a mutation in a pleiotropic gene may have an effect on some or all traits simultaneously. This can become a problem when selection on one trait favors one specific version of the gene (allele), while the selection on the other trait favors another allele.

Etymology

The term pleiotropy comes from the Greek πλείων pleion, meaning "more", and τροπή tropí, meaning "turn, convert". A common mistake is to use "pleiotrophic" instead of "pleiotropic"^{[citation needed]}.

History

The term "pleiotropie" was coined in a 1910 Festschrift written by the german geneticist Ludwig Plate, a former student of Ernst Haeckel. The term "polyphaeon" was also suggested in 1925 by Haeckel but did not persist^[1]. Even before the term was proposed there were examples of distinct traits that seemed to be inherited together. In his classic 1866 paper, Gregor Mendel listed his trait number three in peas as having brown seed coat, violet flowers, and axial spots.

Mechanism

Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. The underlying mechanism is that the gene codes for a product that is, for example, used by various cells, or has a signaling function on various targets.

A classic example of pleiotropy is the human disease PKU (phenylketonuria). This disease can cause mental retardation and reduced hair and skin pigmentation, and can be caused by any of a large number of mutations in a single gene that codes for the enzyme (phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine, another amino acid. Depending on the mutation involved, this results in reduced or zero conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to toxic levels, causing damage at several locations in the body. PKU is totally benign if a diet free from phenylalanine is maintained.

Antagonistic pleiotropy

Antagonistic pleiotropy refers to the expression of a gene resulting in multiple competing effects, some beneficial but others detrimental to the organism.

This is central to a theory of aging first developed by G. C. Williams in 1957.^[2] Williams suggested that some genes responsible for increased fitness in the younger, fertile organism contribute to decreased fitness later in life. An example is the p53 gene, which suppresses cancer, but also suppresses stem cells, which replenish worn-out tissue^[3].

Whether or not pleiotropy is antagonistic may depend upon the environment; for instance, a bacterial gene that enhances glucose utilization efficiency at the expense of the ability to use other energy sources (such as lactose) has positive effects when there is plenty of glucose, but can be lethal if lactose is the only available food source.

Evolution

Pleiotropy of genes impacts the evolutionary rate of genes. Traditionally it has been expected that evolutionary rate of genes is related negatively with pleiotropy, however this has not been clearly found in empirical data ^[4][5]. Contrary to this traditional expectation, it has been theoretically demonstrated that evolutionary rate should be positively related with pleiotropy by itself as the square root of gene pleiotropy ^[6], however other effects of pleiotropy may explain why a clear relationship between evolutionary rate and gene pleiotropy has not been found at genomic scale ^[6].

See also

• Epistasis
• Metabolic network
• Metabolic supermice
• Enhancer (genetics)

References

1. ^ Stearns, F. W. (2010). One Hundred Years of Pleitropy: A Retrospective. Genetics 186(3):767-773. http://www.genetics.org/content/186/3/767.abstract
2. ^ Williams, G.C. (1957) Pleiotropy, natural selection, and the evolution of senescence. Evolution 11: 398–411
3. ^ Rodier F, Campisi J, Bhaumik D (2007). "Two faces of p53: aging and tumor suppression". Nucleic Acids Res 35 (22): 7475–84. doi:10.1093/nar/gkm744. PMC 2190721. PMID 17942417. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2190721. 
4. ^ Pál, C. et al. (2001). Highly expressed genes in yeast evolve slowly. Genetics 158:927–931.
5. ^ Camps, M. et al. (2007). Genetic constraints on protein evolution. Crit. Rev. Biochem. Mol. 42:313-326.
6. ^ ^{a b} Razeto-Barry, P. et al. (2011). Molecular Evolution, Mutation Size and Gene Pleiotropy: a Geometric Reexamination. Genetics 187(3):877-885. http://www.genetics.org/content/187/3/877.abstract

External links

• Pleiotropy is 100 years old