D.V. CLARK, BSc (UBC), PhD (SFU). 1) Genetics of purine nucleotide biosynthesis and 2) Functional analysis of gene duplications in the fruit fly Drosophila melanogaster.
Biology Undergraduate Advisor
Biol 1001 (Biological Principles, Part I)
4082 (Advanced Genetics)
Biol 4533 (Bioinformatics)
Two different areas of research focus on 1) the regulation and role of purine nucleotide synthesis genes in animal development and 2) functional analysis of gene duplications. 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 currently examining the relationship between purine gene regulation and pathways involved in cell proliferation, stress, and aging. In addition, the cellular and developmental effects of purine depletion are being examined. 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 regulation of purine gene expression.
Another area of research arose from our studies on a duplicated pair of purine synthesis genes, Prat and Prat2, which both encode the enzyme amidophosphoribosyltransferase, yet are not redundant in function. Both are essential genes for fly development and they have diversified with respect to their expression patterns in development, where Prat is exclusively expressed in the female germline and imaginal tissue and Prat2 is expressed in the fat body. The analysis of this gene duplication, which appears to have occured by a retrotransposition event, served as a starting point for our second research program focusing on the functional analysis of gene duplication by retrotransposition in Drosophila.
Holland C., Lipsett D.B., and Clark, D.V. (2011) A link between impaired purine nucleotide synthesis and apoptosis in Drosophila melanogaster. Genetics Jun;188(2):359-67.
Hackett, J.M. and D.V. Clark. (2009) Modifiers of Prat, a de novo purine synthesis gene, in Drosophila melanogaster. Genome 52(11): 957–967.
Penney, J., J. Bossé J. and D.V. Clark. (2008) Expression pattern diversity and functional conservation between retroposed PRAT genes from Drosophila melanogaster and Drosophila virilis. J Mol Evol. May;66(5):457-471.
Langille, Morgan G. I., and D. V. Clark. (2007) Parent genes of retrotransposition-generated gene duplicates in Drosophila melanogaster have distinct expression profiles. Genomics, Sep;90(3):334-43.
Ji, Y. and D. V. Clark. (2006) The purine synthesis gene Prat2 is required for Drosophila metamorphosis, as revealed by inverted-repeat-mediated RNA interference. Genetics, Mar;172(3):1621-31.
Malmanche, N., and D. V. Clark. (2004) Drosophila melanogaster Prat, a purine de novo synthesis gene, has a pleiotropic maternal effect phenotype. Genetics, Dec;168(4):2011-23.
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.
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Last Update: 01 September 2011
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