Have you ever run into an unexpected detour on your commute? Whether it be an ice patch, flood, or even a mudslide, mother nature can reroute even the best laid plans, but for some species, changes in the environment have much higher stakes than being late for work or that much needed vacation.
In fact, many species of fish undergo complete sex reversal to adapt to environmental detour signs, including the bluehead wrasse, a coral reef dwelling species where the largest females fully transition when no other males are present. Although this dramatic detour is clearly beneficial, we still don’t understand what signal sets it off or which molecules are involved.
The labs of Timothy Hore, Neil Gemmel (University of Otago, New Zealand), and John Godwin (North Carolina State University, USA), who were the first to assemble the bluehead wrasse genome, decided to explore the molecular and epigenetic landscape of this transformation. The talented team sampled brain and gonadal tissue from fish before, after, and during 6 stages of the transition and used RNA-seq to find that:
- The brain transcriptome barely changes between the stages while the gonadal gene expression profile is strongly varied
- Gene expression changes in the gonads fall into 4 broad patterns during the transition:
- Female-related (oogenic) gene expression decreases
- Male-related (spermatogenic) gene expression increases
- Some genes are more expressed during the transitionary phases than in either fully differentiated state, and are enriched for immune response and proliferation genes
- Other genes are more highly expressed at both differentiated endpoints and are related to protein kinase activity
- The earliest genes that are tuned off in both the brain and the gonads are cyp19a1a and cyp19a1b, which code for aromatase enzymes that converts testosterone to estradiol
- Some genes that are highly sex-specific in mammalian gonads have paralogs that show the opposite expression pattern in wrasses
- Early stages of transition show high expression of genes involved in cortisol production and stress signalling which suggests that stress might be an important trigger for sex change
The talented team also found that key epigenetic modifiers, including members of the Polycomb repressive complex 2 (PRC2), histone acetyltransferases and deacetylases, and DNA methylation machinery (DNMT3As and TET) fluctuate throughout the transition. They used whole genome bisulfite sequencing (WGBS) to examine the DNA methylation profiles of their gonad samples and found that:
- Gonads progressively accumulate cytosine methylation as they transition from ovaries to testes
- Genomic regions that overlap with female-expressed genes gain methylation whereas regions overlapping with male-specific genes lose methylation as fish transition
- Just like transcriptomes, the gonadal methylomes cluster by transitionary stage according to principal component analysis (PCA)
These riveting results suggest that environmental roadblocks, including social cues, are perceived as stressors that start the epigenetic engine driving sex reversal in these fish. They also suggest that it’s not a non-stop route from ovary to testes and that the stages in-between might be distinct pit stops along the road!
If you’re feeling road-weary, take a rest stop with Science Advances, July 2019.