Subterranean Fishes of the World

3263

2017

AIM 2017

The cave morph of Astyanax mexicanus has a number of anatomical and physiological differences from the surface morph including increased number of facial hair cells and lack of eyes and pigmentation. Several critical eye development genes are down-regulated in the cave compared to the surface morph, however, the mechanism down-regulating these genes is largely unknown. Previous studies on eye specification genes did not identify any inactivating mutations in the coding regions. This observation suggested that other mechanisms including epigenetic and cisregulatory changes may down-regulate gene expression in cavefish eyes. Here, we report a role for DNA methylation in cavefish eye gene repression. We performed RNA sequencing and whole genome bisulfite sequencing (WGBS) from isolated surface and cave morph embryonic eyes. Combined analyses of the RNA and WGBS revealed that more than three hundred genes show both down-regulation and promoter hypermethylation. Further analysis revealed that out of the top thirty-five down-regulated and hypermethylated genes, twenty-two genes are associated with human eye disorders. We also found that QTLs responsible for the retinal thickness in cavefish eyes contain genes from this category. These observations suggest DNA methylation based gene repression may be an important mechanism responsible for down-regulation of multiple eyespecific gene expression, and contribute to the reduced eye phenotype. We also found upregulation of Dnmt3bb.1 transcripts in isolated eyes of both the Pachon and Sabinos cave morphs, suggesting changes in DNA methylation may be a common mechanism for modulating eye-specific gene expression in cave-adapted Astyanax.

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