Transcriptome dynamics predict thermotolerance in Caenorhabditis elegans

Abstract

20The detrimental effects of a short bout of stress can persist, and potentially turn lethal, long after the return 21 to normal conditions. Thermotolerance, which is the capacity of an organism to withstand relatively extreme 22 temperatures, is influenced by the response during stress exposure, as well as the recovery process 23 afterwards. While heat-shock response mechanisms have been studied intensively, predicting thermal 24 tolerance remains a challenge. Here, we use the nematode Caenorhabditis elegans to measure 25 transcriptional resilience to heat stress and predict thermotolerance. Using high dimensionality reduction 26 techniques in combination with genome-wide gene expression profiles collected in three high resolution 27 time-series during control, heat stress and recovery conditions, we infer a quantitative scale capturing the 28 extent of stress-induced transcriptome dynamics in a single value This scale provides a basis for evaluating 29 transcriptome resilience, defined here as the ability to depart from stress-expression dynamics during 30 recovery. Independent replication across multiple highly divergent genotypes reveals that the transcriptional 31 resilience parameter measured after a spike in temperature is quantitatively linked to long-term survival 32 after heat stress. Our findings imply that thermotolerance is an intrinsic property that pre-determines long 33 term outcome of stress and can be predicted by the transcriptional resilience parameter. Inferring the 34 transcriptional resilience parameters of higher organisms could aid in evaluating rehabilitation strategies 35 after stresses such as disease and trauma. 36

Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

“…Thus, N2 showed a IPR to OrV infection, however we did not detect increased expression of IPR genes in CB4856 nematodes. Yet, the IPR can also be activated by heat stress and by re-analyzing a previous dataset we observed that pals-genes were activated after heat shock in CB4856 (Supplemental Text S2, Supplemental Figure S7) (Jovic et al, 2017(Jovic et al, , 2019. Therefore, the lack of a transcriptional response 30h post OrV infection could result from early activation of IPR genes or the infection stress being too mild stress to trigger the IPR.…”

“…(Supplemental Text S2, Supplemental Figure S7) (Jovic et al, 2017(Jovic et al, , 2019. Therefore, the lack of a transcriptional response 30h post OrV infection could result from early activation of IPR genes or the infection stress being too mild stress to trigger the IPR.…”