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

ABSTRACT

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.

KEYWORDS:

• DNA methylation
• RRBS
• sexual dimorphism
• teleosts
• muscle growth
• Oreochromis niloticus

Acknowledgments

We are thankful to Hilde Ribe, Steinar Johnsen, Øivind Torslett and particularly to Kaspar Klaudiussen (Nord University, Norway) for their assistance with fish husbandry.

Authors’ contributions

TP carried out the wet lab and bioinformatics analysis, interpreted the results, and wrote the article. SB contributed significantly to wet lab analysis (DNA extraction and RRBS protocol) and revised the article. IK contributed significantly to sampling, to bioinformatics analysis and revised the article. JMOF conceived the study, designed the experiment, provided reagents, and contributed significantly to wet lab analysis, bioinformatics analysis, interpretation of results, and article revision. All authors read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics statement

All procedures involving animals were performed according to the guidelines of the Norwegian Animal Research Authority (FOTS ID 1042) and approved by the Nord University (Norway) ethics committee.

Supplemental material

Supplemental data for this article can be accessed here.

Additional information

Funding

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme [grant agreement no 683210] and from the Research Council of Norway under the Toppforsk programme [grant agreement no 250548/F20].