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Relaxed Selection Limits Lifespan by Increasing Mutation Load

R. Cui, T. Medeiros, D. Willemsen, LNM. Iasi, GE. Collier, M. Graef, M. Reichard, DR. Valenzano,

. 2019 ; 178 (2) : 385-399.e20. [pub] 20190627

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20023826

To uncover the selective forces shaping life-history trait evolution across species, we investigate the genomic basis underlying adaptations to seasonal habitat desiccation in African killifishes, identifying the genetic variants associated with positive and relaxed purifying selection in 45 killifish species and 231 wild individuals distributed throughout sub-Saharan Africa. In annual species, genetic drift led to the expansion of nuclear and mitochondrial genomes and caused the accumulation of deleterious genetic variants in key life-history modulating genes such as mtor, insr, ampk, foxo3, and polg. Relaxation of purifying selection is also significantly associated with mitochondrial function and aging in human populations. We find that relaxation of purifying selection prominently shapes genomes and is a prime candidate force molding the evolution of lifespan and the distribution of genetic variants associated with late-onset diseases in different species. VIDEO ABSTRACT.

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$a Medeiros, Tania $u Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
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$a Willemsen, David $u Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
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$a Iasi, Leonardo N M $u Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
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$a Collier, Glen E $u Department of Biological Science, University of Tulsa, Tulsa, OK 74104, USA.
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$a Graef, Martin $u Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; CECAD, University of Cologne, 50931 Cologne, Germany.
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$a Reichard, Martin $u The Czech Academy of Sciences, Institute of Vertebrate Biology, 603 65 Brno, Czech Republic.
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$a Valenzano, Dario Riccardo $u Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; CECAD, University of Cologne, 50931 Cologne, Germany. Electronic address: dvalenzano@age.mpg.de.
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