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Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

机译:秀丽隐杆线虫线虫寿命,免疫力和抗逆性的表型协方差

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Background Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. Methodology/Principal Findings We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. Conclusions The gonochoristic species display a significantly longer lifespan (p0.0001) and more robust immune and stress response (p0.0001, thermal stress; p0.01, heavy metal stress; p0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants.
机译:背景技术老化,免疫力和压力耐受性是所有生物的固有特征。在动物中,这些性状至少部分受到叉头转录因子的调节,以响应来自胰岛素/胰岛素样生长因子信号传导(IIS)途径的上游信号。在线虫秀丽隐杆线虫中,这些表型是分子连接的,因此叉头转录因子DAF-16的激活既延长了寿命,又同时提高了免疫力和抗逆性。众所周知,秀丽隐杆线虫之间的寿命差异很大,尽管DAF-16信号传导高度保守,但尚不清楚该表型连锁是否在其他物种中发生。在这里,我们通过比较四种秀丽隐杆线虫的寿命,抗逆性和免疫力来研究这种表型协方差。方法/主要发现我们通过对DAF-16影响表型的表型分析表明,在四个密切相关的秀丽隐杆线虫中,生殖生殖物种(Remanei隐杆线虫和brenneri隐杆线虫)的分化显着,寿命更长,抗应激性更高,免疫力比雌激素高。种(秀丽隐杆线虫和Caenorhabditis briggsae)。有趣的是,我们还使用实时PCR在这些物种的daf-16同源物之间观察到表达水平的显着差异,这与所观察到的表型呈正相关。最后,我们通过使用野生型分离株,组成型活性daf-16突变体和生物信息学分析的组合,提供了其他证据来支持DAF-16在调节表型偶联中的作用。结论与雌雄同体的物种相比,性腺变种具有更长的寿命(p <0.0001)和更强的免疫和应激反应(p <0.0001,热胁迫; p <0.01,重金属胁迫; p <0.0001,致病胁迫)。我们的数据表明,DAF-16介导的表型的差异可能是这四种线虫秀丽隐杆线虫之间观察到的许多差异的基础。这些发现进一步得到了促性腺激素相关物种中较高的daf-16表达水平以及组成性活性daf-16雌雄同体突变体中显着更高的寿命,免疫力和胁迫耐受性的支持。

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