Accumulation of Detrimental Mutations Cause for Premature Aging in Killifish

Researchers at the Max Planck Institute for Biology of Ageing made use of African killifish to investigate how different lifespan strategies have evolved in nature, as different African killifish species vary extensively in their lifespans—from just a few months to several years.

They sequenced and analysed the genome of 45 African killifish species and found that short-lived species have an expanded genome, full of highly redundant DNA sequences between and within genes. Additionally, the genome of the short-lived fish accumulates detrimental mutations, including in genes coding for central processes, such as DNA repair, metabolism control, mitochondrial function and in other known aging genes.

These findings suggest that natural selection does not work as efficiently for genes important in late life and relaxed selection prominently shapes the evolution of lifespan and the distribution of genetic variants associated with late-onset diseases in different species.

It doesn’t matter if a mutation makes you a little bit sick when you are old, because you have reproduced already and transmitted that mutation to your offspring. We found that this basic principle explains the expanded genome and the accumulation of detrimental mutations in short-lived killifish.

Dario Valenzano, senior author