Abstract
Author SummaryA large proportion of the diversity of living organisms results from differential regulation of gene transcription. Transcriptional regulation is thought to differ between species because of evolutionary changes in the physical interactions between regulatory DNA elements and DNA-binding proteins; these can generate variation in the spatial and temporal patterns of gene expression. The mechanisms by which these protein–DNA interactions evolve is therefore an important question in evolutionary biology. Does adaptive evolution play a role, or is the process dominated by neutral genetic drift? Insulator proteins are a special group of DNA-binding proteins—instead of directly serving to activate or repress genes, they can function to coordinate the interactions between other regulatory elements (such as enhancers and promoters). Additionally, insulator proteins can limit the spreading of chromatin condensation and help to demarcate the boundaries of regulatory domains in the genome. In spite of their critical role in genome regulation, little is known about the evolution of interactions between insulator proteins and DNA. Here, we use ChIP-seq to examine the distribution of binding sites for CTCF, a highly conserved insulator protein, in four closely related Drosophila species. We find that genome-wide binding profiles of CTCF are highly dynamic across evolutionary time, with frequent births of new CTCF-DNA interactions, and we demonstrate that this evolutionary process is driven by natural selection. By comparing these with RNA-seq data, we find that gain or loss of CTCF binding impacts the expression levels of nearby genes and correlates with structural evolution of the genome. Together these results suggest a potential mechanism of regulatory re-wiring through adaptive evolution of CTCF binding.
Highlights
Gene regulation is a major driver in the generation of morphological diversity [1,2]
Simulans, D. yakuba, and D. pseudoobscura, we used chromatin collected from white pre-pupae (WPP) at puparium formation, a developmental stage induced by rising titres of the metamorphosis hormone 20-hydroxyecdysone [38]
CCCTC binding factor (CTCF) binding profile replicates within a species for the same strain were highly reproducible and recapitulated the well-characterized binding peaks previously identified within the Bithorax complex genomic region in D. melanogaster (Figure S2) [13,23]
Summary
Gene regulation is a major driver in the generation of morphological diversity [1,2]. Transcriptional regulators determine spatial and temporal patterns of mRNA level by binding to cis-regulatory DNA elements. Many previous studies have demonstrated that changes at the level of protein-DNA interactions can account for specific phenotypic differences observed in nature [1,3]. Genome-wide studies have shown that binding of transcriptional regulators evolves substantially between different species [4,5,6,7,8,9]. In Drosophila, the binding profiles of some regulatory factors involved in embryonic development, such as the Twist protein, are relatively more conserved [5,8]. In order to address this question, regulatory factors must be mapped in multiple related species and the results interpreted in the light of intraspecific and interspecific cisregulatory DNA variation
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