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

Abstract

AbstractDifferences 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 byC. elegansresearchers (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 genefln-2in the male stock, which reduces early mortality caused by pharyngeal infection. We show howfln-2variation explains previous discrepancies involving effects ofsir-2.1(sirtuin deacetylase) on ageing, and show that in afln-2(+)background,sir-2.1over-expression causes an FUDR (DNA synthesis inhibitor)-dependent reduction in pharyngeal infection and increase in lifespan. In addition we show howfln-2variation confounds effects on lifespan ofdaf-2(insulin/IGF-1 signalling),daf-12(steroid hormone signalling), andeat-2(putative dietary restriction). These findings underscore the importance of identifying and controlling genetic background variation.