Pleiotropy

Pleiotropy

[plahy-o-truh-pee]
Pleiotropy occurs when a single gene influences multiple phenotypic traits. Consequently, a new mutation in the gene will have an effect on all traits simultaneously. This can become a problem when selection on one trait favours one specific mutant, while the selection at the other trait favors another mutant.

Etymology

The term pleiotropy comes from the Greek πλείων pleion, meaning "more", and τρέπειν trepein, meaning "to turn, to convert". A common mistake is to use "pleiotrophic" instead of "pleiotropic"

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 signalling 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 an enzyme (phenylalanine hydroxylase) that 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. Williams suggested that some genes responsible for increased fitness in the younger, fertile organism contribute to decreased fitness later in life. One such example in male humans is the gene for the hormone testosterone. In youth, testosterone has positive effects including reproductive fitness but, later in life, there are negative effects such as increased susceptibility to prostate cancer. Another example is the p53 gene which suppresses cancer, but also suppresses stem cells which replenish worn-out tissue.

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.

See also

References

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