There are three basic levels of control of aging: 1) the proximate causes leading to senesence in particular cell lines or tissues, 2) regulatory processes that integrate these proximate causes into an individual's aging pattern, and 3) evolutionary forces that operate upon these individual aging patterns to determine the aging pattern characteristic of the species. We have and will continue to study the control of aging at all these levels with abnormal abdomen (aa) syndrome in the fruit-fly, Drosophila mercatorum. Our past work on aa revealed it is a complex polygenic trait characterized by extensive epistasis centered around a major locus on the X-chromosome. Further genetic studies will be performed. Molecular studies will also be done. We now know the major locus is associated with insertions into the coding region of the 28S ribosomal genes found on the X-chromosome. In addition, a male-specific modifier of aa is a deletion of the 18S-28S genes normally found on the Y. The immediate impact of these insertions and deletions is to greatly alter patterns of transcription of the ribosomal genes. These transcriptional effects in turn apparently lead to many developmental manifestations, including a slow down of aging during the larval phase but a speed-up of aging during the adult phase. We intend to investigate how the various transcriptional patterns might lead to these aging effects, and particularly the phenomenon of heterochrony that exists in aa flies: unequal aging rates in different cell lines causing new patterns of traits to co-occur. Finally, the aa genes exist in high frequency in certain natural populations, and natural populations can be surveyed using a recently developed single fly protocol for scoring ribosomal DNA variants. Our past field work has made use of the fact that we can determine the age of wild-caught flies. We now intend to couple this ability with our ability to probe for molecular variants in single wild-caught flies. This will allow us to determine the aging patterns associated with the various aa genotypes in nature and to make strong quantitative inferences about the adaptive significance of the various aa-associated aging patterns. Our past work has already strongly indicated that high levels of adult mortality induced by dessication play the dominant adaptive role in determining the frequency of aa in nature.
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