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  Relaxed Selection Limits Lifespan by Increasing Mutation Load

Cui, R., Medeiros, T. C., Willemsen, D., Iasi, L., Collier, G. E., Graef, M., et al. (2019). Relaxed Selection Limits Lifespan by Increasing Mutation Load. Cell, 178(2), 385-399 e20. doi:10.1016/j.cell.2019.06.004.

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 Creators:
Cui, R.1, Author           
Medeiros, T. C.2, Author           
Willemsen, D.1, Author           
Iasi, L.N.M.1, Author           
Collier, G. E., Author
Graef, M.2, Author           
Reichard, M., Author
Valenzano, D. R.1, Author           
Affiliations:
1Valenzano – Evolutionary and Experimental Biology of Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942297              
2Graef – Autophagy and Cellular Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_1942295              

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Free keywords: aging distribution of fitness effects genome evolution human genetics killifishes life history lifespan mitochondrial dysfunction mutation rate neutral evolution
 Abstract: 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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 Dates: 2019-07-112019-07-02
 Publication Status: Issued
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 Identifiers: Other: 31257025
DOI: 10.1016/j.cell.2019.06.004
ISSN: 1097-4172 (Electronic)0092-8674 (Linking)
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Title: Cell
Source Genre: Journal
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Pages: - Volume / Issue: 178 (2) Sequence Number: - Start / End Page: 385 - 399 e20 Identifier: -