Antagonistic pleiotropy and mutation accumulation influence human senescence and disease
Rodríguez, J.A.; Marigorta, U.M.; Hughes, D.A.; Spataro, N.; Bosch, E.; Navarro, A. (2017)
Nature Ecology and Evolution 1(3):55. doi: 10.1038/s41559-016-0055
Human ageing has long been a public health issue as well as a fascinating evolutionary problem. This paper gives support, at a genome-wide level, to two of the most well-known theories of ageing: The Mutation Accumulation (MA) and the Antagonistic Pleiotropy (AP). As theoretically predicted by MA, we observe higher risk allele frequencies (panel A) combined with large effect sizes for late-onset diseases (panel B). Also, and in concordance with AP, we found that human genomes carry a significant excess of variants, increasing reproductive fitness at young ages, but at the cost of an increased risk for some age-related diseases later on, when humans are no longer fertile anymore (panel C).