Relaxed Selection Limits Lifespan by Increasing Mutation Load

Highlights

• Whole-genome sequences of 45 African killifish species

• Relaxed selection leads to larger genomes in short-lived, annual killifish

• Population bottlenecks affect the distribution of aging variants in fish and humans

• Natural polg variants in annual killifish cause high rate of mtDNA mutations

Summary

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.

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