Epigenetic mapping of the somatotropic axis in Nile tilapia reveals differential DNA hydroxymethylation marks associated with growth.

In vertebrates, the somatotropic axis comprising the pituitary gland, liver and muscle plays a major role in myogenesis. Its output in terms of muscle growth is highly affected by nutritional and environmental cues, and thus likely epigenetically regulated. Hydroxymethylation is emerging as a DNA modification that modulates gene expression but a holistic characterization of the hydroxymethylome of the somatotropic axis has not been investigated to date. Using reduced representation 5-hydroxymethylcytosine profiling we demonstrate tissue-specific localization of 5-hydroxymethylcytosines at single nucleotide resolution. Their abundance within gene bodies and promoters of several growth-related genes supports their pertinent role in gene regulation. We propose that cytosine hydroxymethylation may contribute to the phenotypic plasticity of growth through epigenetic regulation of the somatotropic axis.

Differences in brain gene transcription profiles advocate for an important role of cognitive function in upstream migration and water obstacles crossing in European eel.

BACKGROUND: European eel is a panmictic species, whose decline has been recorded since the last 20 years. Among human-induced environmental factors of decline, the impact of water dams during species migration is questioned. The main issue of this study was to pinpoint phenotypic traits that predisposed glass eels to successful passage by water barriers. The approach of the study was individual-centred and without any a priori hypothesis on traits involved in the putative obstacles selective pressure. We analyzed the transcription level of 14,913 genes. RESULTS: Transcriptome analysis of three tissues (brain, liver and muscle) from individuals sampled on three successive forebays separated by water obstacles indicated different gene transcription profiles in brain between the two upstream forebays. No differences in gene transcription levels were observed in liver and muscle samples among segments. A total of 26 genes were differentially transcribed in brain. These genes encode for, among others, keratins, cytokeratins, calcium binding proteins (S100 family), cofilin, calmodulin, claudin and thy-1 membrane glycoprotein. The functional analysis of these genes highlighted a putative role of cytoskeletal dynamics and synaptic plasticity in fish upstream migration. CONCLUSION: Synaptic connections in brain are solicited while eels are climbing the obstacles with poorly designed fishways. Successful passage by such barriers can be related to spatial learning and spatial orientation abilities when fish is out of the water.

Early fish domestication affects methylation of key genes involved in the rapid onset of the farmed phenotype.

Animal domestication is a process of environmental modulation and artificial selection leading to permanent phenotypic modifications. Recent studies showed that phenotypic changes occur very early in domestication, i.e., within the first generation in captivity, which raises the hypothesis that epigenetic mechanisms may play a critical role on the early onset of the domestic phenotype. In this context, we applied reduced representation bisulphite sequencing to compare methylation profiles between wild Nile tilapia females and their offspring reared under farmed conditions. Approximately 700 differentially methylated CpG sites were found, many of them associated not only with genes involved in muscle growth, immunity, autophagy and diet response but also related to epigenetic mechanisms, such as RNA methylation and histone modifications. This bottom-up approach showed that the phenotypic traits often related to domestic animals (e.g., higher growth rate and different immune status) may be regulated epigenetically and prior to artificial selection on gene sequences. Moreover, it revealed the importance of diet in this process, as reflected by differential methylation patterns in genes critical to fat metabolism. Finally, our study highlighted that the TGF-ß1 signalling pathway may regulate and be regulated by several differentially methylated CpG-associated genes. This could be an important and multifunctional component in promoting adaptation of fish to a domestic environment while modulating growth and immunity-related traits.

Differences in the fast muscle methylome provide insight into sex-specific epigenetic regulation of growth in Nile tilapia during early stages of domestication.

Growth is a complex trait whose variability within a population cannot be explained solely by genetic variation. Epigenetic regulation is often suggested as an important factor shaping the phenotype, but its association with growth can be highly context- and species-dependent. Nevertheless, the mechanisms involved in epigenetic regulation of growth in fish are poorly understood. We have used reduced representation bisulphite sequencing to determine the genome-wide CpG methylation patterns in male and female Nile tilapia of different sizes but at the same early stage of domestication. The average CpG methylation level in the reduced genome representation was 63% across groups but many sites displayed group-specific methylation patterns. The number of differentially methylated (DM) CpGs was much higher when the interaction between sex and weight was included rather than when these factors were considered separately. There were 1128 DM CpGs between large and small females and 970 DM CpGs between large and small males. We have found many growth-related genes associated with DM CpGs, namely map3k5 and akt3 in females and gadd45g and ppargc1a in males. Only 5% of CpG locations associated with growth were common to both sexes. In particular, the autophagy-related gene atg14 displayed a high association of methylation with growth exclusively in males. The sexually dimorphic association between atg14 methylation and growth may uncover novel metabolic mechanisms at play during mouth brooding in Nile tilapia females. Taken together, our data suggest that epigenetic regulation of growth in Nile tilapia involves different gene networks in males and females.