Identification of European se bass neomales through epigenomic analysis

Abstract

The European sea bass is a teleost with polygenic sex determination (PSD), where genetics and environmental factors contribute to sex ratios. However, in farming, many fish that would become females under natural conditions develop as phenotypic males, called neomales. Identifying males that produce progeny resistant to the masculinizing effects of elevated temperature is desirable. However, neomales are indistinguishable genetically from regular females and transcriptomically from regular males. Here, we compared the gonadal epigenome of heat-resistant females (n=23) and neomales (n=24) of six different families obtained from the cross of the same female with six different males. After several data pre-processing steps of more than 1,4 x10^6 CpGs we filtered out the 118,2x10^3 DMCs between testes (n=24) and ovaries (n= 23) to eliminate differences due to tissue. We ended up with 128,1 x10^3 most variable regions of 200 bp each. Then we applied multi-omics factor analysis (MOFA) taking as informative layers promoters, exons, introns and CpG islands (D=1000). The unsupervised model revealed four hidden factors. Factor 1 discriminated neomales from females and allowed the identification of biomarkers such as a CpG in the sfxn2 promoter, the methylation of which was higher in females than in neomales. To our knowledge, this constitutes the first example where epigenetics is used to reveal differences in the susceptibility of the gonads to high temperature in a PSD species