Background |
Ross MacIntyre is Professor of Genetics in the Department of Molecular Biology & Genetics and also a member of the Graduate Field of Ecology and Evolutionary Biology. He received a B.A. in Biology at Gonzaga University in 1960 and a Ph.D. in Genetics (Cytology) at The Johns Hopkins University in 1964. He was a National Institutes of Health Postdoctoral Fellow with Dr. Bruce Wallace at Cornell University from 1964-66. He joined the faculty at Cornell in 1966, became a full professor in 1978, and was Chairman of the Section from 1985-1990. Dr. MacIntyre was a recipient of a Guggenheim Award in 1980-1981, and served on the National Institutes of Health Study Section in Genetics (1984-1988). He is currently an Associate Editor of the Journal of Heredity (1987-present) and is also the editor of an annual series of books entitled Evolutionary Biology. He is a member of the Genetics Society of America,the Society for the Study of Evolution, and the Society for Molecular Biology and Evolution. |
Research Description |
There are three projects currently under investigation in my laboratory. First we are carrying out genetic and molecular analyses of two genes whose enzymes, alpha-glycerophosphate dehydrogenasealpha (alphaGPDH) in the cytoplasm and alpha-glycerophosphate oxidase (alphaGPO) in the mitochondrion, are responsible for the continued production of ATP in the Dipteran insect flight muscle. The accompanying diagram illustrates the roles of the two enzymes in the so called alpha-glycerophosphate cycle. We have mapped, cloned and sequenced both genes in Drosophila melanogaster. Null mutants for either enzyme survive to adulthood but cannot fly. alphaGPDH consists of three isoforms, resulting from the differential splicing of three C terminal exons. In the flight muscle, the C terminal exon specifies three amino acids which anchor the protein at the Z line. Correct alphaGPDH localization is essential for the Z line localization of at least two other glycolytic enzymes, aldolase and glyceraldehyde-3-phosphate dehydrogenase. We are currently assessing the role of different mutant forms of the flight muscle specific alphaGPDH in assembling this putative glycolytic enzyme complex, and its association with the structural proteins of the myofibril. alphaGPDH and alphaGPO will also be used to study the evolution of the order Diptera. We are cloning the homologous alphaGPDH and alphaGPO genes from other Drosophila species, the housefly, the blackfly and the mosquito Anopheles gambiae. A comparison of the sequence differences in the coding regions will allow us to begin a phylogenetic reconstruction of the order and establish a time frame for its evolution. Evolutionary changes in the regulation and function of the two enzymes will be examined via transformation of the genes from the other Dipteran species into single and double null mutant hosts from D. melanogaster. In addition to assaying the ability of the heterologous enzymes to supply the missing enzymatic activity (i.e. will the mutant Drosophila now be able to fly, and, if so how well?), we will determine if the genes from the other species are properly regulated (i.e. is the gene product from another Dipteran species found in the right tissues at the right times during development, and, if not, why not?)
In the second project, we are studying the molecular evolution of cytochrome P450 genes whose products allow four species of Drosophila to utilize, as host plants, four diferent columnar cacti from the Sonoran desert from the Southwestern United States and Northern Mexico. The P450 enzymes break down the normally toxic alkaloids present in the cacti. After cloning these genes, we will establish their role in detoxification via their transformation into Drosophila melanogaster (which cannot survive on the cacti) and determine the contributions of structural and regulatory genes to this adaptation. We are also mapping the members of this large P450 multigene family on the polytene chromosomes of the four species by in situ hybridization of biotinylated probes.
Thirdly we are analyzing the structure and the product of the complex dumpy gene in Drosophila melanogaster. Mutants of this huge gene - which are recovered at unusually high frequencies - can affect singly, or in various combinations, three different phenotypes. This very large gene has been cloned via a chromosomal walk, and its dimensions are being determined from the positions of mutant breakpoints and by analyses of its messenger RNAÕs. We want to understand the nature of the dumpy gene product and its role in imaginal wing disc differentiation, the nature of the various mutant phenotypes, the spatial relationships of the various kinds of dumpy mutants within the gene, and, finally, whether the large size of this gene (currently over 200 kilobases) is an evolutionarily conserved. |
Selected Publications |
- A genetic analysis of the alpha-glycerophosphate oxidase locus in Drosophila melanogaster. Genetics 120:755-766 (1988). With M.B. Davis.
- Structural characterization of the alphaGPDH gene of Drosophila melanogaster. Proc. Nat'l. Acad. Sci. USA 86:5020-5024 (1989). With L. Von Kalm, J. Weaver, J. DeMarco, and D. Sullivan.
- The isolation and identification of the acid phosphatase-1 gene from Drosophila melanogaster. Mol. Gen. Genet. 224:49-56. (1990). With C. Shaffer.
- Molecular Evolution: Codes, clocks, genes and genomes. Bioessays 16:699-0703 (1994).
- Molecular characterization of the lysosomal acid phosphatase from Drosophila melanogaster. Mol. Gen. Genet. 250:635-646 (1996). With H.J. Chung, and C. Shaffer.
Click here to view Dr. MacIntyre's PubMed listings. |
