Antagonistic pleiotropy hypothesis
[8] Antagonistic pleiotropy also provides a framework for understanding why many genetic disorders, even those causing life threatening health impacts (e.g. sickle cell anaemia), are found to be relatively prevalent in populations.
Seen through the lens of simple evolutionary processes, these genetic disorders should be observed at very low frequencies due to the force of natural selection.
These tradeoffs can result from selection at the level of the organism or, more subtly, via mechanisms for the allocation of scarce resources in cellular metabolism.
This genetic balancing act determines how many individuals survive to flower in a short growing season (viability) while also influencing the seed set of survivors (fecundity).
The authors find that tradeoffs between plant viability and fecundity can engender a stable polymorphism under surprisingly general conditions.
However, in terms of cardiovascular risk, these same inflammatory responses have turned out to be harmful as the material conditions of human existence improved – in affluent countries, where life expectancy is much longer than in the ancestral environment, strong inflammatory responses carry greater risks of cardiovascular disease as individuals age.
It also linked specific alleles to a combination of higher fertility, stronger inflammatory response and greater cardiovascular problems in old age.
This finding supports the hypothesis that this gene was prevalent because it helped women in the ancestral environment to more effectively combat infection during their reproductive years.
[15] The survival of many serious genetic disorders in human evolutionary history has led researchers to explore the role of antagonistic pleiotropy in disease.
[18] In another study of genetic diseases, 99 individuals with Laron syndrome (a rare form of dwarfism) were monitored alongside their non-dwarf kin for a period of ten years.
Laron syndrome patients experienced a lower incidence of cancer mortality and diabetes compared to their non-dwarf kin.
[9] Another instance of antagonistic pleiotropy is manifested in Huntington's disease, a rare neurodegenerative disorder characterized by a high number of CAG repeats within the Huntingtin gene.
The onset of Huntington's is usually observed post-reproductive age and generally involves involuntary muscle spasms, cognitive difficulties and psychiatric problems.
[20] It is generally accepted that the evolution of secondary sexual characteristics persists until the relative costs of survival outweigh the benefits of reproductive success.
Rowe and Houle answer this question (the lek paradox) using the notion of genetic capture, which couples the sexually-selected traits with the overall condition of the organism.
Thus proteins that regulate the level of DNA repair activity appear to have the antagonistic pleiotrophic effect of being beneficial during youthful development, but insufficient to prevent aging during maturity.
