Antagonistic pleiotropy hypothesis

Strength of natural selection plot as a function of age

The antagonistic pleiotropy hypothesis (APT) is a theory in evolutionary biology that suggests certain genes may confer beneficial effects early in an organism's life, enhancing reproductive success, while also causing detrimental effects later in life, contributing to the aging process.

APT was first proposed in a 1952 paper on the evolutionary theory of ageing by Peter Medawar and developed further in a paper by George C. Williams in 1957[1] as an explanation for senescence.[2] Pleiotropy is the phenomenon where a single gene influences more than one phenotypic trait in an organism.[3][4] It is one of the most commonly observed attributes of genes.[5] A gene is considered to exhibit antagonistic pleiotropy if it controls more than one phenotypic trait, where at least one of these traits is beneficial to the organism's fitness and at least one is detrimental to fitness.

This line of genetic research began as an attempt to answer the following question: if survival and reproduction should always be favoured by natural selection, why should ageing – which in evolutionary terms can be described as the age-related decline in survival rate and reproduction – be nearly ubiquitous in the natural world?"[2] The antagonistic pleiotropy hypothesis provides a partial answer to this question. As an evolutionary explanation for ageing, the hypothesis relies on the fact that reproductive capacity declines with age in many species and, therefore, the strength of natural selection also declines with age (because there can be no natural selection without reproduction).[6][7] Since the strength of selection declines over the life cycles of human and most other organisms, natural selection in these species tends to favor "alleles that have early beneficial effects, but later deleterious effects".[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. Genetic models of populations show that antagonistic pleiotropy allows genetic disorders to be maintained at reasonably high frequencies "even if the fitness benefits are subtle".[9] In this sense, antagonistic pleiotropy forms the basis of a "genetic trade-off between different fitness components."[10]

  1. ^ Williams GC (1957). "Pleiotropy, natural selection, and the evolution of senescence". Evolution. 11 (4): 398–411. doi:10.2307/2406060. JSTOR 2406060.
  2. ^ a b Austad SN, Hoffman JM (2018). "Is antagonistic pleiotropy ubiquitous in aging biology?". Evolution, Medicine, and Public Health. 2018 (1): 287–294. doi:10.1093/emph/eoy033. PMC 6276058. PMID 30524730.
  3. ^ Cheverud J (1996). "Developmental integration and the evolution of pleiotropy". American Zoology. 36: 44–50. CiteSeerX 10.1.1.526.8366. doi:10.1093/icb/36.1.44.
  4. ^ He X, Zhang J (August 2006). "Toward a molecular understanding of pleiotropy". Genetics. 173 (4): 1885–1891. doi:10.1534/genetics.106.060269. PMC 1569710. PMID 16702416.
  5. ^ Otto SP (April 2004). "Two steps forward, one step back: the pleiotropic effects of favoured alleles". Proceedings. Biological Sciences. 271 (1540): 705–714. doi:10.1098/rspb.2003.2635. PMC 1691650. PMID 15209104.
  6. ^ Elena SF, Sanjuán R (December 2003). "Evolution. Climb every mountain?". Science. 302 (5653): 2074–2075. doi:10.1126/science.1093165. PMID 14684807. S2CID 83853360.
  7. ^ Flatt T (May 2011). "Survival costs of reproduction in Drosophila" (PDF). Experimental Gerontology. 46 (5): 369–375. doi:10.1016/j.exger.2010.10.008. PMID 20970491. S2CID 107465469.
  8. ^ Rose MR, Rauser CL (2007). "Evolution and Comparative Biology". Encyclopedia of Gerontology. 2: 538–547. doi:10.1016/B0-12-370870-2/00068-8. ISBN 978-0-12-370870-0.
  9. ^ Cite error: The named reference Carter_2011 was invoked but never defined (see the help page).
  10. ^ Brown KE, Kelly JK (January 2018). "Antagonistic pleiotropy can maintain fitness variation in annual plants". Journal of Evolutionary Biology. 31 (1): 46–56. doi:10.1111/jeb.13192. PMID 29030895.