Antagonistic pleiotropy hypothesis

The antagonistic pleiotropy hypothesis was first proposed by George C. Williams in 1957 as an evolutionary explanation for senescence. Pleiotropy is the phenomenon where one gene controls for more than one phenotypic trait in an organism. Antagonistic pleiotropy is when one gene controls for more than one trait, where at least one of these traits is beneficial to the organism's fitness and at least one is detrimental to the organism's fitness. The theme of G.C. William's idea about antagonistic pleiotropy was that if a gene caused both increased reproduction in early life and aging in later life, then senescence would be adaptive in evolution. For example, one study suggests that since follicular depletion in human females causes both more regular cycles in early life and loss of fertility later in life through menopause, it can be selected for by having its early benefits outweigh its late costs. The antagonistic pleiotropy hypothesis was first proposed by George C. Williams in 1957 as an evolutionary explanation for senescence. Pleiotropy is the phenomenon where one gene controls for more than one phenotypic trait in an organism. Antagonistic pleiotropy is when one gene controls for more than one trait, where at least one of these traits is beneficial to the organism's fitness and at least one is detrimental to the organism's fitness. The theme of G.C. William's idea about antagonistic pleiotropy was that if a gene caused both increased reproduction in early life and aging in later life, then senescence would be adaptive in evolution. For example, one study suggests that since follicular depletion in human females causes both more regular cycles in early life and loss of fertility later in life through menopause, it can be selected for by having its early benefits outweigh its late costs. Antagonistic pleiotropy is one of the several reasons evolutionary biologists give for organisms never being able to reach perfection through natural selection. Antagonistically pleiotropic genes are the explanation for fitness trade-offs. This means that genes that are pleiotropic control for some beneficial traits and some detrimental traits; thus, if they happen to persist through natural selection, this will prevent organisms from reaching perfection because if they possess the benefits of the gene, they must also possess the imperfections or faults. An example of this would be female rodents that live in a nest with other females and may end up feeding young that are not theirs due to their intense parental drive. This strong parental drive will be selected for, but the organisms will still make the mistake of feeding young that are not theirs and misallocating their resources. Antagonistic pleiotropy has several negative consequences. It results in delayed adaptation, an altered path of evolution, and reduced adaptation of other traits. In addition, the overall benefit of alleles is cut down significantly (by about half) by pleiotropy. Still, antagonistic pleiotropy has some evolutionary benefits. In fact, the conservation of genes is directly related to the pleiotropic character of an organism. This implies that genes that control for multiple traits, even if the traits have different implications for the organism's fitness, have more staying power in an evolutionary context. It is generally accepted that the evolution of secondary sexual characteristics persists until the relative costs of survival outweigh the benefits of reproductive success. At the level of genes, this means a trade-off between variation and expression of selected traits. Strong, persistent sexual selection should result in decreased genetic variation for these traits. However, higher levels of variation have been reported in sexually-selected traits compared to non-sexually selected traits. This phenomenon is especially clear in lek species, where males confer no immediate advantage to the female. Female choice presumably depends on correlating male displays (secondary sexual characteristics) with overall genetic quality. If such directional sexual selection depletes variation in males, why would female choice continue to exist? 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. They posit that the genes for secondary sexual characteristics must be pleiotropically linked to condition, a measure of the organism's fitness. In other words, the genetic variation in secondary sexual characteristics is maintained due to variation in the organism's condition. The survival of many serious genetic disorders in our long evolutionary history has led researchers to reassess the role of antagonistic pleiotropy in disease. If genetic disorders are defined by the existence of deleterious alleles, then natural selection acting over evolutionary time would result in a lower frequency of mutations than are currently observed. In a recent article, Carter and Nguyen identify several genetic disorders, arguing that far from being a rare phenomenon, antagonistic pleiotropy might be a fundamental mechanism for the survival of these non-optimal alleles. In one of these studies, 99 individuals with Laron syndrome (a rare form of dwarfism) were monitored alongside their non-dwarf kin for a period of ten years. Patients with Laron syndrome possess one of three genotypes for the growth hormone receptor gene (GHR). Most patients have an A->G splice site mutation in position 180 in exon 6. Some others possess a nonsense mutation (R43X), while the rest are heterozygous for the two mutations. Laron syndrome patients experienced a lower incidence of cancer mortality and diabetes compared to their non-dwarf kin. This suggests a role for antagonistic pleiotropy, whereby a deleterious mutation is preserved in a population because it still confers some survival benefit. 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. Incidentally, the high number of CAG repeats is associated with increased activity of p53, a tumor suppressing protein that participates in apoptosis. It has been hypothesized that this explains the lower rates of cancer among Huntington's patients. Huntington's disease is also correlated with high fecundity. Additionally, it was found that individuals with a higher pro-inflammatory ratio TNFα/IL-10 had a significantly higher incidence of death due to cardiovascular disease in old age. Yet, it was hypothesized that this genotype was prevalent because higher ratios of TNFα/IL-10 allow individuals to more effectively combat infection during reproductive years. Sickle cell anemia, Beta-thalassemia, and cystic fibrosis are some other examples of the role antagonistic pleiotropy may play in genetic disorders.