Abstract
Thermotolerance of an organism is a complex trait that is influenced by a multitude of genetic and environmental factors. Many factors controlling thermotolerance in Caenorhabditis elegans are known to extend life. To understand the regulation of thermotolerance, we performed a genetic screen for mutants with better survival at warm temperature. Here we identified by dauer survival a tax-2 mutation and several mutations disrupting an insulin signaling pathway including the daf-2 gene. While the tax-2 mutant has improved thermotolerance and long life span, the newly identified daf-2 and other insulin signaling mutants, unlike the canonical daf-2(e1370), do not show improved thermotolerance despite being long-lived. Examination of tax-2 mutations and their mutant phenotypes suggest that the control of thermotolerance is not coupled with the control of life span or dauer survival. With genetic interaction studies, we concluded that tax-2 has complex roles in life span and dauer survival and that tax-2 is a negative regulator of thermotolerance independent of other known thermotolerance genes including those in the insulin signaling pathway. Moreover, cold growth temperature during development weakens the improved thermotolerance associated with tax-2 and other thermotolerance-inducing mutations. Together, this study reveals previously unknown genetic and environmental factors controlling thermotolerance and their complex relationship with life span regulation.
Highlights
The ability of a living organism to survive high temperature, or thermotolerance, could be related to molecular mechanisms of stress response and life span regulation
We started with a proposition that mutants that could reproduce at normally inhospitable temperature have improved thermotolerance and that a direct genetic screen of such mutant is feasible
We started a genetic screen looking for mutants that could reproduce at the restrictive temperature of 28◦C starting with N2 and at 26.5◦C starting with hsf-1(sy441) hoping to identify new thermotolerance genes
Summary
The ability of a living organism to survive high temperature, or thermotolerance, could be related to molecular mechanisms of stress response and life span regulation. Loss-of-function mutation in daf-16 FOXO, which acts downstream of daf-2 in the insulin branch dauer pathway, suppresses both life span extension and improved thermotolerance conferred by mutations in both the insulin branch and TGFβ dauer pathways (Hsu et al, 2003; Shaw et al, 2007). Another major focus in the study of C. elegans thermotolerance is the gene hsf-1 heat shock transcription factor (Garigan et al, 2002). Other reports suggest that the daf-2 and hsf-1 control of thermotolerance are not coupled to their control of life span (Wolff et al, 2006; McColl et al, 2010; Douglas et al, 2015), and the presence and the nature of shared underlying mechanism between these biological processes overall are unclear
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