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.