Long-lived rodents reveal signatures of positive selection in genes associated with lifespan and eusociality

Sahm, A.; Bens, M.; Szafranski, K.; Holtze, S.; Groth, M.; Goerlach, M.; Calkhoven, C.; Mueller, C.; Schwab, M.; Kestler, H. A.; Cellerino, A.; Burda, H.; Hildebrandt, T.; Dammann, P.; Platzer, M.

doi:10.1101/191999

bioRxiv · 10.1101/191999

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan and eusociality

Sahm, A.·Bens, M.·Szafranski, K.·Holtze, S.·Groth, M.·Goerlach, M.·Calkhoven, C.·Mueller, C.·Schwab, M.·Kestler, H. A.·Cellerino, A.·Burda, H.·Hildebrandt, T.·Dammann, P.·Platzer, M.

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Abstract

The genetic mechanisms that determine lifespan are poorly understood. Most research has been done on short lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. We obtained genomic and transcriptomic data from 17 rodent species and systematically scanned eleven lineages associated with the evolution of longevity and eusociality for positively selected genes (PSGs). The set of 319 PSGs contains regulators of mTOR and is enriched in functional terms associated with (i) processes that are regulated by the mTOR pathway, e.g. translation, autophagy and mitochondrial biogenesis, (ii) the immune system and (iii) antioxidant defense. Analyzing gene expression of PSGs during aging in the long-lived naked mole-rat and up-regulation in the short-lived rat, we found a pattern fitting the antagonistic pleiotropy theory of aging.

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Sahm, A., Bens, M., Szafranski, K., Holtze, S., Groth, M., Goerlach, M., Calkhoven, C., Mueller, C., Schwab, M., Kestler, H. A., Cellerino, A., Burda, H., Hildebrandt, T., Dammann, P., Platzer, M.. 2017-09-21. Long-lived rodents reveal signatures of positive selection in genes associated with lifespan and eusociality. https://doi.org/10.1101/191999

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