Phenotypic covariance of longevity, immunity and stress resistance in the caenorhabditis nematodes.
Phenotypic covariance of longevity, immunity and stress resistance in the caenorhabditis nematodes.
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DOI：
10.1371/journal.pone.0009978
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发表时间：
2010-04-01
期刊：
影响因子：
3.7
通讯作者：
May RC
中科院分区：
文献类型：
--
作者：
Amrit FR;Boehnisch CM;May RC
衰老、免疫和应激耐受性是所有生物体的固有特征。在动物中，这些性状至少在一定程度上受到叉头转录因子对胰岛素/胰岛素样生长因子信号通路上游信号的调节。在秀丽隐杆线虫中，这些表型在分子上是相互关联的，因此激活叉头转录因子DAF-16既延长了寿命，又增加了免疫力和抗逆性。众所周知，在Caenorhabditis物种之间的寿命差异很大，但是，尽管DAF-16信号是高度保守的，但尚不清楚这种表型连锁是否发生在其他物种中。在这里，我们通过比较四种隐杆线虫的寿命、抗逆性和免疫力来研究这种表型协方差。通过对DAF-16影响的表型进行表型分析，我们发现，在四种密切相关的隐杆线虫中，雌雄同体的隐杆线虫（隐杆线虫和布伦纳隐杆线虫）明显分化，其寿命更长，抗逆性更好，免疫力更高，而雌雄同体的隐杆线虫（秀丽隐杆线虫和briggsae隐杆线虫）更强。有趣的是，我们还通过Real-Time PCR观察到这些物种中daf-16同源物的表达水平存在显著差异，这与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，提供了支持DAF-16在调节表型偶联中的作用的额外证据。雌雄同体比雌雄同体表现出更长的寿命（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介导的表型差异可能是这四种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相关的高daf-16表达水平的支持，并且组成活性daf-16雌雄同体突变体的寿命、免疫力和应激耐受性显著提高。
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. 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. The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, 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.