Development of epigenetic biomarkers with diagnostic and prognostic value to assess the lasting effects of early temperature changes in farmed fish

Abstract

Epigenetic changes such as DNA methylation modifications at specific loci in the genome in response to environmental cues can appear long before the appearance of transcriptomic or other phenotypic changes with potential consequences for performance. Thus, epigenetic DNA methylation-based biomarkers hold great promise in aquaculture and conservation biology because they can have prognostic value. However, to the best of our knowledge, a clear demonstration of such biomarkers has not been provided yet. Temperature during early stages of development is the main abiotic factor determining larval quality, with effects potentially persisting until adulthood and influencing performance. The objective of this study was to test whether epigenetic biomarkers could be developed as reliable indicators of the quality of the thermal environment during European sea bass (Dicentrarchus labrax) early development and their relation to long-lasting phenotypic consequences. We exposed European sea bass embryos and newly hatched larvae to different temperature regimes and sampled fish thereafter at three time points: at larval, juvenile and adult stages. Here, we provide an analytical strategy combining Reduced Representation Bisulfite sequencing (RRBS) and RNA-sequencing (RNA-seq) to develop epigenetic and transcriptomic biomarkers with both prognostic and diagnostic value. Specifically, we report a series of DNA-methylation biomarkers linked to short-term, mid-term, long-term, and very-long term effects of temperature in both somatic and reproductive tissues. Among the different biomarkers identified, one promising example is the methylation status of keratin-associated protein 10–4 (krtap10–4), which fulfills the criteria of an epigenetic biomarker with both prognostic and diagnostic value. This study constitutes a first step toward providing the European sea bass farming sector with a set of epigenetic biomarkers that can be used to screen batches of larvae to determine the quality of their thermal environment and to anticipate their performance when juveniles and adults. Our study provides the way for similar developments for other species, farmed or not.