A role for environmental epigenetics in the rapid diversification of East African cichlid fishes

Phenotypic plasticity via gene-environment interaction is a central feature of regulatory biology. By definition, phenotypic plasticity involves a change in gene regulation. These gene regulatory transitions are commonly mediated by an array of epigenetic mechanisms, which exert dynamic, environmentally responsive control over the genome. In vertebrates, these mechanisms include regulation via histone posttranslational modifications, DNA methylation, and non-coding RNAs. By regulating genetic processes in response to external signals, epigenetic mechanisms have an evident role in phenotypic adaptation. Recent explorations have revealed that the eukaryotic epigenome detects and responds to a range of environmental inputs, including nutrition, temperature, and toxicant exposure. However, studies in environmental epigenetics have focused primarily on DNA methylation, leaving the role of other epigenetic mechanisms largely unexplored. This is particularly true regarding vertebrate models. Moreover, very few studies in vertebrates show robust support for the link between epigenetics and adaptive plasticity. The relevance of other epigenetic mechanisms in vertebrate gene-environment interactions remains unclear. Here, I use East African cichlid fishes—a model system for phenotypic plasticity and rapid evolution—to decipher the role of chromatin regulation in the establishment of phenotypic diversity in novel environments. To illustrate chromatin state dynamics genome-wide, I focus on four major histone modifications associated with enhancer/promoter activity and gene silencing: H3K4me3, H3K27ac, H3K4me1, and H3K27me3. I began by establishing natural epigenetic variability in a lake environment. On the basis of ecomorphological diversity and genetic similarity, four species were selected from Lake Malawi, an ecosystem containing the most extensive cichlid adaptive radiation, which houses more fish species than any other lake in the world. Using Cut&Run, I profiled genome-wide enrichment of the chosen histone modifications in adult males from each species. Incorporating a supervised model to integrate mark enrichment with gene expression, I defined a set of functional chromatin states in Malawi cichlids. Results from differential binding analysis reveal ecotype-specific regulatory variation in key metabolic and developmental pathways, reflecting trophic adaptation and regulation of alternate developmental trajectories. To date, these results present the most comprehensive characterization of chromatin features in cichlid fishes. To further dissect the influence of environment on the epigenome, I present an experiment simulating short-term nutritional adaptation in a controlled setting. Here, I supply generalist cichlid Astatotilapia calliptera with two alternate diets, formulated to mimic piscivorous and algivorous trophic regimes. Within one generation of this experiment, fish of each diet treatment developed novel craniofacial and body shape morphologies, accompanied by changes in relative eye size, brain size, pigmentation, and growth patterns. To study the epigenetic basis of these phenotypic changes, I measured chromatin landscape variation in liver from each treatment. Interestingly, the regulatory differences between treatments occur in the same pathways identified as most variable between the Malawi ecotypes, in patterns that emulate the standing epigenetic variation in the lake. In these investigations, I detect consistent patterns of epigenetic variation in conspecific treatment groups under environmental stress and between species phylogenetically separated by thousands of years. In the context of cichlid trophic expansion, I conclude that chromatin regulatory mechanisms might mediate dietary adaptation through modulation of metabolic pathways in a conserved crosstalk between genes and environment