Divergent evolution toward sex chromosome-specific gene regulation in Drosophila

  1. Peter B. Becker1
  1. 1Molecular Biology Division, Biomedical Center, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany;
  2. 2Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany;
  3. 3Core Facility Bioimaging, Biomedical Center, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany;
  4. 4Protein Analysis Unit, Biomedical Center, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany;
  5. 5Bioinformatics Unit, Biomedical Center, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany
  1. Corresponding authors: pbecker{at}bmc.med.lmu.de, raffaella.villa{at}med.uni-muenchen.de

Abstract

The dosage compensation complex (DCC) of Drosophila identifies its X-chromosomal binding sites with exquisite selectivity. The principles that assure this vital targeting are known from the D. melanogaster model: DCC-intrinsic specificity of DNA binding, cooperativity with the CLAMP protein, and noncoding roX2 RNA transcribed from the X chromosome. We found that in D. virilis, a species separated from melanogaster by 40 million years of evolution, all principles are active but contribute differently to X specificity. In melanogaster, the DCC subunit MSL2 evolved intrinsic DNA-binding selectivity for rare PionX sites, which mark the X chromosome. In virilis, PionX motifs are abundant and not X-enriched. Accordingly, MSL2 lacks specific recognition. Here, roX2 RNA plays a more instructive role, counteracting a nonproductive interaction of CLAMP and modulating DCC binding selectivity. Remarkably, roX2 triggers a stable chromatin binding mode characteristic of DCC. Evidently, X-specific regulation is achieved by divergent evolution of protein, DNA, and RNA components.

Keywords

Footnotes

  • Received February 26, 2021.
  • Accepted May 4, 2021.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

| Table of Contents

Life Science Alliance