Evolution of chromatin accessibility associated with traits of cichlid phenotypic diversity

The radiations of cichlid fishes in East African Lakes Victoria, Malawi, and Tanganyika showcase a remarkable example of rapid adaptive speciation, with over 2000 species evolving diverse morphological and ecological adaptations within the last few million years. Understanding the molecular basis of this phenotypic diversity remains a key challenge. Building on prior evidence of gene regulatory network (GRN) rewiring underpinning adaptive traits, we profiled chromatin accessibility (ATAC-seq) and matched transcriptomes across brain, eye, liver, and testis tissues in five representative cichlid species using optimised protocols. We show extensive divergence in chromatin accessibility corresponding to phylogenetic lineages and tissue identity, with many regulatory regions exhibiting accelerated nucleotide evolution. Transcription factor binding site (TFBS) variation correlates with both chromatin accessibility and differential gene expression, particularly in genes linked to sensory systems. By integrating TF footprinting with regulatory motif turnover analyses, we demonstrate that dynamic nucleotide changes drive GRN rewiring, concordant with ecological niche and lineage-specific adaptations. Our findings highlight regulatory variation at conserved and novel TFBSs as critical drivers of phenotypic innovation across radiating and non-radiating East African cichlids. This study provides foundational epigenomic evidence establishing GRN divergence as a key mechanism facilitating rapid adaptive diversification in this iconic vertebrate radiation.