Epigenetic modification and inheritance in sexual reversal of fish

Abstract

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, cooccurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

Epigenetic regulation of sex ratios may explain natural variation in self-fertilization rates

“…These genes had been previously identified as being involved in sex reversal regulated by temperature and controlled by DNA methylation [36,40]. We found significantly higher levels of methylation in males incubated at low temperature compared with the other three groups (hermaphrodites at low temperature and males and hermaphrodites at high temperature for Sox9a; figure 3a).…”

“…The inactivation of one X chromosome in female mammals [46] is a well-known example of epigenetic control, and there are indications that there is a similar mechanism in some dioecious plants [57]; experimental modification of DNA methylation in plants has also been shown to induce sex reversal [58]. For some time DNA methylation was hypothesized to be involved in sex determination of fish [59], and more recently methylation of the gonadal aromatase promoter (cyp 19a) has been related to the regulation of temperature-mediated sex ratios in two fish with environmental and genetic sex determination, the European sea bass (Dicentrarchus labrax) [40] and the half-smooth tongue sole (Cynoglossus semilaevis) [36], suggesting that DNA methylation is indeed a crucial mechanism linking environmental temperature and sex determination in some fish species.…”

“…Epigenetic regulation of gene expression during gonad differentiation is involved in the adaptive sex reversal observed in some fish and other organisms with genetic sex determination [45]. For example, methylation has been related to sexual reversal in relation to incubation temperature in the half-smooth tongue sole [36]. This is because, although also linked to genomic imprinting [46], transposon immobilization [47] and suppression of transcriptional noise [48], the major biological consequence of DNA methylation throughout plants, fungi and animals is gene silencing [49].…”

“…Converted DNA concentration was then assessed using a NanoDrop 1000 spectrophotometer with the RNA setting. PCRs for cyp19a and dmrt1 were carried out using primers designed for Japanese flounder as described by Shao et al [36]. PCRs for Sox9a were carried out using primers designed for alligator by Parrott et al [37].…”

Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes

“…; Table 1), showed heat responses with delayed effects, as their expression was altered in adults but not in juveniles following termination of the heat treatment. These results indicate that heat-induced masculinization likely requires or involves epigenetic mechanisms and, based on the evidence from other fish species (70,71), further studies should focus on transgenerational effects of heat and investigate whether these lasting effects could be detected in subsequent generations.…”