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REVIEW: What Is Antagonistic Pleiotropy?

J. Mitteldorf1,2,a

1Washington University School of Medicine, St. Louis, MO 63110, USA

2National Institute for Biological Sciences, 102206 Beijing, China

Received July 5, 2019; Revised September 19, 2019; Accepted September 19, 2019
Antagonistic Pleiotropy (AP) is today the best-accepted theory for the evolutionary origin of aging. According to AP theory, aging is a side effect of genes that are selected for their contribution to fertility and other essential components of individual fitness. In this standard view, aging exists because the benefits of enhanced fertility early in life are linked logically or physically to the long-term deterioration of the body, and evolution has been compelled to accept the latter as a cost of the former. What is the evidence for this proposition? Indeed, biological aging has sometimes been observed to be genetically associated with enhancement of fertility or survivability early in life, but the association is not universal or consistent. There are known examples of mutations that lead to longer lifespan without apparent cost. This is a major problem for AP theory, because AP theory supposes that senescence could never have evolved on its own, and (according to AP theory) there should be a substantial fitness dividend for any individual that manages to extend its lifespan without curtailing its fertility. How can we understand the observed fact that genetic mechanisms of aging are sometimes pleiotropic and sometimes not? I propose herein an alternative interpretation, in which antagonistic pleiotropy is not a precondition imposed on evolution, but an evolved adaptation in its own right. My hypothesis is that aging is selected because of important long-term benefits for the community, but in the short term, individual selection is stronger than group selection. Therefore, the communal benefits are in danger of being lost. Antagonistic pleiotropy evolves as an evolvability adaptation that protects long term group-level benefits from being lost to short term individual selection. The mechanism of selection is indirect, the benefit long-term, and it accrues only to the group at the expense of the individual. By standard population genetic reasoning, selection for pleiotropy should be too weak to matter; but in our individual-based simulation, pleiotropy evolves consistently under a broad swath of parameter space. A key feature of the model contributing to the viability of group adaptations is the assumption of a predator species in a geographically structured population, such that any population that evolves a reproduction rate exceeding the local prey population is punished by high rates of starvation. The combination of high fertility and long lifespan is a temptation for individuals, but a danger for the stability of populations. Once a sustainable mix of fertility and longevity has been established by multilevel natural selection, pleiotropy can help to assure that it is not lost. The population is free to shift from (high fertility/short lifespan) to (lower fertility/longer lifespan) as varying environmental conditions demand, without risking population overshoot and collapse.
KEY WORDS: aging, senescence, programmed aging, antagonistic pleiotropy, group selection, multilevel selection

DOI: 10.1134/S0006297919120058