TitleThermosensitive splicing of a clock gene and seasonal adaptation
NameLow, Kwang Huei (author), Edery, Isaac (chair), Gunderson, Samuel (internal member), Belden, William (internal member), Liu, Fang (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectMicrobiology and Molecular Genetics,
DescriptionPrior work showed that the thermosensitive splicing of an intron found in the 3’ untranslated region (UTR) of the Drosophila melanogaster period (per) gene, termed dmpi8 (Drosophila melanogaster per intron 8), is critical for temperature-induced adjustments in the distribution of daily activity. Using a simplified cell culture system, we showed that an intricate balance between multiple suboptimal splicing signals is the underlying molecular basis for the thermosensitive splicing of dmpi8. We confirmed the physiological significance of this model in transgenic Drosophila by altering the splice site strengths of dmpi8. Presumably, at higher temperatures, the interaction between the spliceosome and the sub-optimal splicing signals is weaker and hence results in less efficient splicing. Further studies of Drosophila species from different geographical regions strongly suggest that the thermal regulation in the splicing efficiency of the D. melanogaster per 3’-terminal intron is an important mechanism for seasonal adaptation in this species. Temperature dependent splicing of dmpi8 contributed to the ability of cosmopolitan D. melanogaster to adapt to temperate regions by providing a mechanism that can extent midday siesta during the long warm days typical of temperate climates. However, Drosophila species indigenous to Afro-equatorial regions, wherein temperature undergoes little seasonal variation, do not exhibit thermal adjustments in their daily activity patterns. Intriguingly, 3’-terminal introns were also found in their per genes, but these introns have strong splice sites and are not spliced in a thermosensitive manner. Thus, the strengths of key splicing signals underlies species-specific differences in the thermosensitivities of per 3’-terminal intron removal that correlate with the ability to adjust daily activity patterns in a temperature dependent manner. In related work we identified natural polymorphisms in non-intronic regions of the per 3’-UTR that modulate dmpi8 splicing. Preliminary analysis suggests that the effects of some of these polymorphisms might be mediated by SR proteins. Finally, we also identified a novel role for the per 3’-terminal intron on sleep homeostasis. In summary, this thesis utilized a multi-faceted strategy, including simplified mechanistic studies and comparative analysis, which led to new ecological and evolutionary perspectives on the role of circadian clock function on thermal and seasonal adaptation.
NoteIncludes bibliographical references
Noteby Kwang Huei Low
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.