Dosage compensation and the rewiring of regulatory netoworks in Drosophila

NIH RePORTER · NIH · R01 · $313,308 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
9908079
Project number
5R01GM076007-14
Recipient
UNIVERSITY OF CALIFORNIA BERKELEY
Principal Investigator
Doris Bachtrog
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$313,308
Award type
5
Project period
2006-04-01 → 2021-02-28