Transcriptome resilience predicts thermotolerance in Caenorhabditis elegans

Katharina Jovic,Basten L Snoek,Mark G Sterken,Jan E Kammenga,Stefano Allesina,Jacopo Grilli,Joost A G Riksen

doi:10.1186/s12915-019-0725-6

Abstract

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

Highlights

The detrimental effects of a short bout of stress can persist and potentially turn lethal, long after the return to normal conditions
Our results show that transcriptome resilience measured after a mild heat stress early in the development of C. elegans is predictive of its thermotolerance
To characterize the temporal dynamics in genomewide gene expression during heat stress and in recovering C. elegans populations, we have to remove stressindependent variation in gene expression patterns caused by differences in development between samples collected in a time series spanning several hours

Summary

Introduction

The detrimental effects of a short bout of stress can persist and potentially turn lethal, long after the return to normal conditions. To the induction of genes within specific stress response pathways, recent studies in C. elegans have shown that heat stress induces a broad acclimation of transcriptional patterns involving differential expression of thousands of genes [7,8,9]. During prolonged stress exposure, expression changed continuously until lethal stress levels were reached [8]. Those findings illustrate that the state of the transcriptome directly reflects the stress levels the organism was exposed to. While the reactive processes occurring during the heat-shock response are well understood, much less is clear about how organisms recover from a heat shock and how the genome-wide transcriptional state might be used to predict longterm outcome of a short bout of heat stress

Methods

Results

Conclusion