Genomic changes that influence gene expression can have significant impacts on the evolution of novel morphological traits and play important roles in diseases such as cancer. While much effort has been dedicated towards defining networks of co-regulated genes, comparatively little is known about the relative importance of processes that result in the recruitment of gene expression regulators to novel and previously unbound locations within the genome. The neo-X chromosome of Drosophila miranda represents an ideal system for studying such processes. This chromosome is young (~1 MYA) yet is already capable of recruiting a regulatory complex which up-regulates gene expression levels across the entire male X chromosome by a factor of two. This process is known as dosage compensation and occurs specifically in males to compensate for their missing X chromosome (e.g. XY versus XX). Genome assemblies from close relatives of D. miranda will be used to identify the mutational path leading to the evolution of the dosage compensation complex binding sites on the neo-X chromosome. From this analysis, it will be possible to determine the relative importance of the various mechanisms by which a binding motif evolves at a novel location in the genome, including de novo evolution from a pre-site or random sequence, transpositions from other genomic locations, or the local amplification of weak binding sites. In addition, polymorphism data from wild D. miranda lines will be analyzed to determine if these binding sites evolved under positive selection, which has implications for the process of Y chromosome degeneration.

Public Health Relevance

This research project seeks to understand basic principles underlying the regulation of gene expression. The results of this project will be relevant to the treatment and diagnosis of human diseases caused by improper regulation of gene expression such as anemia and many types of cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM103186-03
Application #
8706190
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hoodbhoy, Tanya
Project Start
2012-08-20
Project End
2015-08-19
Budget Start
2014-08-20
Budget End
2015-08-19
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Ellison, Christopher E; Bachtrog, Doris (2015) Non-allelic gene conversion enables rapid evolutionary change at multiple regulatory sites encoded by transposable elements. Elife 4:
Zhou, Qi; Ellison, Christopher E; Kaiser, Vera B et al. (2013) The epigenome of evolving Drosophila neo-sex chromosomes: dosage compensation and heterochromatin formation. PLoS Biol 11:e1001711
Alekseyenko, Artyom A; Ellison, Christopher E; Gorchakov, Andrey A et al. (2013) Conservation and de novo acquisition of dosage compensation on newly evolved sex chromosomes in Drosophila. Genes Dev 27:853-8
Ellison, Christopher E; Bachtrog, Doris (2013) Dosage compensation via transposable element mediated rewiring of a regulatory network. Science 342:846-50