Evolutionary innovations and adaptations often require rapid and concerted changes in regulation of gene expression at many loci. Transposable elements (TEs) constitute the most dynamic part of eukaryotic genomes, and insertions of transposable elements can influence the expression of surrounding genes by donating new regulatory elements. A longstanding hypothesis, first proposed by Barbara McClintock, postulates that the dispersal of transposable elements may allow for the same regulatory motif to be recruited at many genomic locations, thereby drawing multiple genes into the same regulatory network. Empirical evidence for this model is however scarce, and most putative examples of TE-mediated rewiring of regulatory networks rely on a statistical association between remnants of a TE at a subset of genes or genomic regions. We recently provided the first direct functional evidence of an active TE rewiring a regulatory network by showing that the acquisition of novel binding sites for the dosage compensation complex at young neo-sex chromosomes in Drosophila was driven by dispersal of a domesticated TE. Here we propose to quantify the involvement of TEs vs. acquisition of regulatory sites by other mutations in rewiring regulatory networks, by systematically studying the evolution of dosage compensation binding sites at over a dozen independently formed young neo-sex chromosomes in Drosophila. Our detailed understanding of how dosage compensation in Drosophila works at the molecular level makes it an ideal model system to study the rewiring of regulatory networks, and recent methodological development make the investigation of binding site evolution at newly formed X chromosomes in non-model Drosophila species feasible, making this a timely and exciting proposal.
Expression networks are often fine-tuned, and chromosomal aneuploidy and changes in gene dosage can disturb the overall balance of gene expression networks, and are associated with several known human diseases and birth defects (Down syndrome results from an extra copy of Chromosome 21), and chromosomal aneuploidies are also frequent in cancer cells. Sex chromosomes, in contrast, provide systems of naturally occurring 'aneuploidy', with females having two X chromosomes and males having one X and a Y, resulting in X monosomy in males, and unique gene regulation strategies have evolved to compensate for this gene-dose deficiency in males. We will use the model species Drosophila to investigate evolutionary and functional aspects of dosage compensation, which will help to understand the effects of aneuploidy on gene expression and the mechanisms that alleviate aneuploidy-induced expression imbalances of the genome.
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