Evolution of Dosage Compensation for Amylase in             Drosophila
{'Code': '08010207', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'DEB', 'LongName': 'Division Of Environmental Biology'}}
{'SignBlockName': 'Gregory J. McCants', 'PO_EMAI': None, 'PO_PHON': None}
Sex-linked dosage compensation is a mechanism of gene                      regulation that results in the level of X-linked gene product                   being equal in both sexes, although males have a single active                  gene copy for the product while females have two.  In Drosophila                miranda, the structural gene for alpha-amylase, Amy, is sex-                    linked and located in a relatively "new" X chromosome, X2, which                evolved in response to an ancestral translocation of one arm of                 an autosome to the Y chromosome.  The unexpressed homolog of Amy                is in the "neo-Y" chromosome of males.  Male and female larvae                  express equivalent levels of amylase activity, suggesting full                  dosage compensation at this developmental stage.  By contrast,                  the compensatory mechanism appears to have been, at best, only                  partially evolved in adults.  Since Amy is not sex-linked in very               closely related Drosophila species - pseudoobscura and                          persimilis, this group of three sibling species provides an                     opportunity to study evolution of a eukaryotic gene regulatory                  mechanism.                                                                           The ultimate goal is to understand the molecular basis of                  dosage compensation for amylase in D. miranda and how it may have               evolved through DNA sequence changes.  Doane and Norman have                    cloned and partially characterized the Amy region of miranda and                isolated a clone that contains the functional Amy gene from its                 X2 chromosome.  They also have begun to characterize dosage                     compensation of Amy expression at the level of amylase messenger                RNA.  The aims of this proposal are to:  (1) complete the amylase               RNA studies and assay dosage compensation at the RNA level in                   male midguts during development; (2) clone and characterize the                 autosomal Amy region of a selected strain of D. persimilis; (3)                 sequence and compare the functional Amy gene and a putative Amy                 pseudogene from miranda and compare the former sequence with the                functional Amy sequence of persimilis; (4) attempt to clone and                 characterize Amy-homologous sequences from the neo-Y chromosome                 of miranda; (5) establish a radiation-induced Amy null (no                      amylase) strain of miranda to provide hosts for Amy gene                        transformation experiments; and (6) delineate the regulatory                    sequences that are important in dosage compensation of Amy                      expression in males of miranda through transformation experiments               coupled with the deletion or alteration of specific DNA sequences               adjacent to the amylase coding region.  Transformation                          experiments, intra- and interspecific, will include both                        transient expression assays ( somatic transformations) and P.                   element-induced germline transformations, both of which entail                  the injection of DNA sequences to be tested in Amy null host                    embryos..Z.  The significance of this basic research lies in the limited        understanding of gene regulatory mechanisms in higher animals.                  This is especially true of mechanisms like Drosophila dosage                    compensation which augments activity of an already                              transcriptionally active gene.  The opportunity provided by the                 amylase system is unique in that the compensatory mechanism is                  not yet fully evolved, so an intermediate stage in DNA sequence                 reorganization leading to it may be analyzed.  Information about                this should add significantly to our understanding of how gene                  regulatory mechanisms may evolve and how important they may be to               the process of evolution.  Such knowledge would be of potential                 value in the application of genetic engineering techniques to                   species in which it would be useful to alter the expression of a                given gene for beneficial or economic reasons, or for                           experimental purposes in population studies.
[{'FirstName': 'Rodney', 'LastName': 'Norman', 'PI_MID_INIT': 'A', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Rodney A Norman', 'EmailAddress': None, 'NSF_ID': '000261325', 'StartDate': '08/01/1988', 'EndDate': None, 'RoleCode': 'Co-Principal Investigator'}, {'FirstName': 'Winifred', 'LastName': 'Doane', 'PI_MID_INIT': 'W', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Winifred W Doane', 'EmailAddress': None, 'NSF_ID': '000129547', 'StartDate': '08/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}]
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[{'Code': '1127', 'Text': 'Evolutionary Processes'}, {'Code': '9120', 'Text': 'CROSS-DIRECTORATE PROGRAMS'}]
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