title: Background-dependent effects of polyglutamine variation in the Arabidopsis thaliana gene ELF3.
abstract: Tandem repeats (TRs) have extremely high mutation rates and are often considered to be neutrally evolving DNA. However, in coding regions, TR copy number mutations can significantly affect phenotype and may facilitate rapid adaptation to new environments. In several human genes, TR copy number mutations that expand polyglutamine (polyQ) tracts beyond a certain threshold cause incurable neurodegenerative diseases. PolyQ-containing proteins exist at a considerable frequency in eukaryotes, yet the phenotypic consequences of natural variation in polyQ tracts that are not associated with disease remain largely unknown. Here, we use Arabidopsis thaliana to dissect the phenotypic consequences of natural variation in the polyQ tract encoded by EARLY FLOWERING 3 (ELF3), a key developmental gene. Changing ELF3 polyQ tract length affected complex ELF3-dependent phenotypes in a striking and nonlinear manner. Some natural ELF3 polyQ variants phenocopied elf3 loss-of-function mutants in a common reference background, although they are functional in their native genetic backgrounds. To test the existence of background-specific modifiers, we compared the phenotypic effects of ELF3 polyQ variants between two divergent backgrounds, Col and Ws, and found dramatic differences. In fact, the Col-ELF3 allele, encoding the shortest known ELF3 polyQ tract, was haploinsufficient in Ws × Col F(1) hybrids. Our data support a model in which variable polyQ tracts drive adaptation to internal genetic environments.
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Soledad Francisca
authors.initials: SF
authors.lastname: Undurraga
authors.forename: Maximilian Oliver
authors.initials: MO
authors.lastname: Press
authors.forename: Matthieu
authors.initials: M
authors.lastname: Legendre
authors.forename: Nora
authors.initials: N
authors.lastname: Bujdoso
authors.forename: Jacob
authors.initials: J
authors.lastname: Bale
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Davis
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Verstrepen
authors.forename: Christine
authors.initials: C
authors.lastname: Queitsch
mesh_terms: D000483:Alleles; D017360:Arabidopsis / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics*; D057906:Circadian Clocks / Q000235:genetics; D003433:Crosses, Genetic; D017343:Genes, Plant / Q000235:genetics*; D057895:Haploinsufficiency / Q000235:genetics; D006824:Hybridization, Genetic; D009154:Mutation / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D010641:Phenotype; D020080:Tandem Repeat Sequences / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D029681:Arabidopsis Proteins; D010455:Peptides; D014157:Transcription Factors; C432430:At2g25930 protein, Arabidopsis; C097188:polyglutamine