Antagonistic Pleiotropy

Antagonistic Pleiotropy is a theory proposed by George C Williams in 1957 suggesting an evolutionary explanation for senescence.

Senescence

Senescence is biological ageing due to the gradual deterioration of functional characteristics of an organism. Senescence can refer to bother cellular senescence whereby cells irreversibly stop dividing without undergoing cell death, or senescence on the scale of the whole organism .

Pleiotropy is a phenomena where one gene influences multiple phenotypic (observed) characteristics, where genes are sequences of DNA nucleotides which act as the basic the unit for genetic inheritance.

Antagonistic Pleiotropy is the instance where a gene that controls a trait which is beneficial to the organism’s fitness early on in life also controls a trait which is detrimental to the organism’s fitness later on in life. A useful way to envisage this is to picture the gene as a scale which weighs heavily to a pro survival trait early on in an organism’s lifetime but as the organism ages the gene shifts to the opposite side of the scale where it favours a anti survival phenotype.(figure 1)

Figure 1: Visualisation of Antagonistically Pleiotropic genes

A whole organism example of senescence controlled by an Antagonistically Pleiotropic gene, is that which codes for the increased production of testosterone in human males. In youths high testosterone levels result in increased fitness, due to factors such as an increased ability to develop muscle mass, and increased sex drive. These both have evolutionary advantages and are beneficial for the elongation of an organism’s life span. However the same gene also has harmful effects, as the individual gets older higher levels of testosterone also puts them at risk of Prostate Cancer. This is an example of an Antagonistically Pleiotropic gene which has been selected for.

A cellular level example of senescence controlled by an Antagonistically Pleiotropic gene is that coding for the enzyme Telomerase. All cells have nuclei which contain genetic information stored as chromosomes. At the end of the chromosomes there are what are essentially DNA caps called Telomeres, which protects the DNA which is stored in the chromosome from being degraded- ie prone to mutation or fragmentation. With each cell division Telomeres shorten, until ,normally around the 60th division, the Telomeres become too short and the DNA is unstable. The cell is then signalled to become senescent and stop dividing. However the enzyme Telomerase, whose production is coded for by DNA, extend the length of Telomeres allowing cells to continue to divide by mitosis.

Figure 2: Telomeres

Therefore one would think that it would make sense that we humans should produce a lot of Telomerase so our cells never die, so humans can have long life spans in which they can produce many offspring. However in reality this doesn’t happen, as increased Telomerase expression is correlated with the uncontrolled cell division associated with cancer. We exist on a knife’s edge balance in regards to Telomerase, which allows Telomeres to shorten rather than remain the same size (as is the case in Tetrahymena cells).Therefore the shortening of Telomeres complies with the Antagonistic Pleiotropy theory, as there is a trade of between the cell benefiting from the expression of Telomerase, as it is balanced in the human body, because it prevents cancerous uncontrolled cell division, but also allows Telomere shortening which is associated by loss of cell functionality.

Genes like the previous 2 examples I have provided, are selected for because they tend to have a larger impact on the organism’s fitness in their prime rather than old age, placing them in a better position to survive and reproduce acting as vectors to proliferate genes to the next generation. Furthermore, Antagonistic Pleiotropy is posited as a reason why organisms can’t reach perfection through evolution because the very genes that code for favourable life span extending characteristics also code for harmful phenotypes.

Bibliography

https://link.springer.com/article/10.1134/S0006297919120058

2-Minute Neuroscience: Basal Ganglia

Telomeres and cell senescence | Cells | MCAT | Khan Academy

The science of cells that never get old | Elizabeth Blackburn

https://en.wikipedia.org/wiki/Antagonistic_pleiotropy_hypothesis

Free radical damage – causes, symptoms, diagnosis, treatment, pathology

https://www.youtube.com/watch?v=2ZRAUO51Wf8

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