title: Natural variation in the Drosophila melanogaster clock gene period modulates splicing of its 3'-terminal intron and mid-day siesta.
abstract: Drosophila melanogaster exhibits circadian (≅24 hr) regulated morning and evening bouts of activity that are separated by a mid-day siesta. Increases in daily ambient temperature are accompanied by a progressively longer mid-day siesta and delayed evening activity. Presumably, this behavioral plasticity reflects an adaptive response that endows D. melanogaster with the ability to temporally optimize daily activity levels over a wide range of physiologically relevant temperatures. For example, the shift in activity towards the cooler nighttime hours on hot days might minimize the risks associated with exposure to mid-day heat, whereas on cold days activity is favored during the warmer daytime hours. These temperature-induced shifts in the distribution of daily activity are partly based on the thermal sensitive splicing of an intron found in the 3' untranslated region (UTR) of the circadian clock gene termed period (per). As temperature decreases, splicing of this 3'-terminal intron (termed dmpi8) is gradually increased, which is causally linked to a shorter mid-day siesta. Herein we identify several natural polymorphisms in the per 3' UTR from wild-caught populations of flies originating along the east coast of the United States. Two non-intronic closely spaced single nucleotide polymorphisms (SNPs) modulate dmpi8 splicing efficiency, with the least efficiently spliced version associated with a longer mid-day siesta, especially at lower temperatures. Although these SNPs modulate the splicing efficiency of dmpi8 they have little to no effect on its thermal responsiveness, consistent with the notion that the suboptimal 5' and 3' splice sites of the dmpi8 intron are the primary cis-acting elements mediating temperature regulation. Our results demonstrate that natural variations in the per gene can modulate the splicing efficiency of the dmpi8 intron and the daily distribution of activity, providing natural examples for the involvement of dmpi8 splicing in the thermal adaptation of behavioral programs in D. melanogaster.
authors.affiliation: Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Kwang Huei
authors.initials: KH
authors.lastname: Low
authors.forename: Wen-Feng
authors.initials: WF
authors.lastname: Chen
authors.forename: Evrim
authors.initials: E
authors.lastname: Yildirim
authors.forename: Isaac
authors.initials: I
authors.lastname: Edery
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001683:Biological Clocks / Q000235:genetics*; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D017344:Genes, Insect / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D007178:Inbreeding; D007438:Introns / Q000235:genetics*; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012890:Sleep / Q000235:genetics; D013997:Time Factors
chemical_list: D029721:Drosophila Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins