A fln-2 mutation affects lethal pathology and lifespan in C. elegans

Yuan Zhao, Hongyuan Wang, Richard J. Poole and David Gems ()
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Yuan Zhao: University College London
Hongyuan Wang: University College London
Richard J. Poole: University College London
David Gems: University College London

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Differences in genetic background in model organisms can have complex effects on phenotypes of interest. We previously reported a difference in hermaphrodite lifespan between two wild-type lines widely used by C. elegans researchers (N2 hermaphrodite and male stocks). Here, using pathology-based approaches and genome sequencing, we identify the cause of this difference as a nonsense mutation in the filamin gene fln-2 in the male stock, which reduces early mortality caused by pharyngeal infection. We show how fln-2 variation explains previous discrepancies involving effects of sir-2.1 (sirtuin deacetylase) on ageing, and show that in a fln-2(+) background, sir-2.1 over-expression causes an FUDR (DNA synthesis inhibitor)-dependent reduction in pharyngeal infection and increase in lifespan. In addition we show how fln-2 variation confounds effects on lifespan of daf-2 (insulin/IGF-1 signalling), daf-12 (steroid hormone signalling), and eat-2 (putative dietary restriction). These findings underscore the importance of identifying and controlling genetic background variation.

Date: 2019
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DOI: 10.1038/s41467-019-13062-z

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