Thursday, 25 October 2012

Pleiotropically Linked Genes

Pleiotropy is defined as the production of two or more unrelated traits by a single gene. Pleiotropy was first described by Mendel in his 1866 paper but the term was not officially coined until 1910 by Ludwig Plate, German geneticist. Pleiotropy has played a role in multiple theories including senescence, direction of selection, adaption and genetic disease. A major goal in genetics is to determine when pleiotropy is caused by a single gene with multiple products and when a single product is incorporated in many different ways.
It was not until the 1970s when gene sequencing became refined enough to shed light on molecular pleiotropic mechanisms. Current research has explored two questions; how extensive is pleiotropy in the genome and how do common mechanisms of pleiotropy work? Whilst originally it was thought that a change to a gene would have a universal effect on an organism recent experiments conducted by molecular geneticists have suggested that there are a few genes that have an effect on a significant number of proteins when they are changed but the majority of genes have little effect to more than one protein.
Dmitry K. Belyaev, a Russian geneticist, did an experiment with foxes. He bred 35 generations with the focus on a single trait, docility. By the end of the experiment the foxes were docile but major physiological traits had changed. The foxes legs and tails had grown shorter, their ears had grown floppy (like dogs) and vixens were now ovulating much more frequently. Clearly the gene responsible for the behavioural changes had also changed proteins responsible for these physical traits.
Pleiotropy can be antagonistic; one trait will be beneficial and another trait detrimental. High testosterone levels in early life will cause an increased level of fitness but will cause an increase to the risk of prostate cancer in later life. The p53 gene when highly expressed suppresses stem cells reducing the replenishment of tissue but reduces the risk of cancer.
Antagonistic pleiotropy is a reason an organism can never reach perfection in its environment. If a gene is pleiotropic and selection favours high expression for one trait and low expression for a different trait then a compromise must be made; middling expression, causing no benefits and no drawbacks.
As the cost of gene sequencing continues to decrease it is becoming more and more feasible to sequence an individual’s genome. Enabling us with the ability to pre-diagnose and treat people for genetic diseases they are likely to have.

Stearns, F.W. 2010, ‘One Hundred Years of Pleiotropy: A Retrospective’, Genetics Society of America, No. 186, pp. 767-773

Trut, L.N. 1996. Early canid domestication: the farm-fox experiment. American Scientist 87:2:160-159.

Gann, P.H., C.H. Hennekens, J. Ma, C. Longcope, M.J. Stampfer. 1996. Prospective Study of Sex Hormone Levels and Risk of Prostate Cancer. Journal of the National Cancer Institute 88:16:1118-1126.


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