D.V. CLARK, BSc (UBC), PhD (SFU).Genetics of purine nucleotide
biosynthesis in the fruit fly Drosophila melanogaster.
Teaching Responsibilities:
Biol 2053 (Genetics)
Biol 4082 (Advanced Genetics)
Biol 4553 (Bioinformatics)
Research Interests:
From studies of purine disorders in humans, it is clear that the
maintenance of the correct level of purine nucleotides is essential
for normal growth and development. Using the fruit fly Drosophila
melanogaster as a model system, we are exploring how the expression
of purine synthesis genes is regulated during animal development.
We are focusing on the Prat gene which encodes the enzyme
that performs the first and rate-determining step in the de novo
purine nucleotide synthesis pathway, amidophosphoribosyltransferase.
We use the tools of genetic analysis, transgenic technology, and
molecular biology to study cis-regulatory DNA sequences and trans-regulatory
gene products important for Prat gene expression.
There is a second
amidophosphoribosyltransferase gene in Drosophila called
Prat2. However, the duplicated Prat genes
are not redundant in function, since Prat is essential
for fly development. In addition, the two genes have distinctive
expression patterns in development, where Prat is exclusively
expressed in the female germline. Consequently, we are generating
mutations in Prat2 to explore its function. In addition,
we are conducting comparative analysis of these two genes in other
insect species to identify conserved sequences and to determine
how the two genes diversified since the duplication event.
The analysis of the Prat gene duplication, which appears
to have occured by a retrotransposition event, serves as a starting
point for a second research program focused on the evolution of
gene duplication by retrotransposition in Drosophila.
Recent Publications:
Malmanche, N., and D. V. Clark. (2003) Identification of trans-dominant modifiers of Prat expression in Drosophila melanogaster. Genetics, Aug;164(4):1419-33.
Malmanche, N., D. Drapeau, P. Cafferty, Y. Ji, D. V. Clark. (2003) The PRAT purine synthesis gene duplication in Drosophila melanogaster and Drosophila virilis is associated with a retrotransposition event and diversification of expression patterns. J. Molecular Evolution 56:630-42.
O'Donnell, A. F., S. Tiong, D. Nash, and D. V. Clark. 2000.
The Drosophila melanogaster ade5 gene encodes a bifunctional
enzyme for two steps in the de novo purine synthesis pathway.
Genetics 154:1239-53
Clark, D. V., and N. MacAfee. 2000. The purine biosynthesis
enzyme PRAT detected in proenzyme and mature forms during development
of Drosophila melanogaster. Insect Biochem. Mol. Biol.
30:315-23
Clark, D.V., J.F. Sabl and S. Henikoff. 1998. Repetitive arrays
containing a housekeeping gene alter polytene chromosome morphology
in Drosophila. Chromosoma, 107:96-104.
Wines, D. R., P. B. Talbert, D. V. Clark and S. Henikoff. 1996.
Introduction of a DNA methyltransferase into Drosophila
to probe chromatin structure in vivo. Chromosoma 104:332-340.
e-mail to: clarkd@unb.ca
Maintained by: casey@unb.ca
Last Update: 9 January 2003
This document: http://www.unb.ca/fredericton/science/biology/Faculty/Clark.html