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Retesting the influences of mutation accumulation and antagonistic pleiotropy on human senescence and disease

Nature Ecology & Evolution volume 3, pages 992–993 (2019)Cite this article

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Matters Arising to this article was published on 24 June 2019

The Original Article was published on 30 January 2017

arising from Rodríguez, J. A. et al. Nature Ecology & Evolution https://doi.org/10.1038/s41559-016-0055 (2017)

Multiple hypotheses have been proposed to explain the origin of senescence, which refers to the gradual deterioration of functional characteristics with ageing1. Two of the leading hypotheses are mutation accumulation (MA)2 and antagonistic pleiotropy (AP)3. The MA hypothesis states that natural selection is ineffective in purging mutations that cause senescence as these mutations have little fitness consequence due to the absence of phenotypic effects until after the reproductive age. The related AP hypothesis asserts that these mutations may even be selectively favoured because they promote growth or reproduction owing to their pleiotropic effects. By examining genetic variants associated with diseases that appear at different life stages, Rodríguez and colleagues claimed to have found genomic evidence for these two hypotheses in humans4. Our further analyses of their data, however, show that their results are not robust and their conclusions unsupported.

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Fig. 1: Retesting the influences of MA and AP on human senescence and disease.

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Authors and Affiliations

  1. Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, USA

    Erping Long & Jianzhi Zhang

  2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

    Erping Long

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  1. Erping Long
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  2. Jianzhi Zhang
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Contributions

E.L. and J.Z. designed the tests and wrote the paper; E.L. analyzed the data.

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Correspondence to Jianzhi Zhang.

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Long, E., Zhang, J. Retesting the influences of mutation accumulation and antagonistic pleiotropy on human senescence and disease. Nat Ecol Evol 3, 992–993 (2019). https://doi.org/10.1038/s41559-019-0925-z

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