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.

MIPSTR: a method for multiplex genotyping of germline and somatic STR variation across many individuals

“…For these loci, our calls were 96% concordant with the Col-0 reference allele, including the highly variable coding STR in the gene ELF3 ( Fig. 2; Undurraga et al 2012).…”

“…Model organism studies have demonstrated significant functional consequences of even subtle unit number variation in select STRs in plants, fungi, flies, voles, dogs, and fish, among other organisms (Sawyer et al 1997;Fondon and Garner 2004;Hammock and Young 2005;Michael et al 2007;Undurraga et al 2012;Scarpino et al 2013;Rosas et al 2014). Similar to humans, STR-containing genes in these organisms tend to be regulatory genes functioning in transcription, development, and sensing environmental factors (Fondon and Garner 2004;Verstrepen et al 2005).…”

“…Similar to humans, STR-containing genes in these organisms tend to be regulatory genes functioning in transcription, development, and sensing environmental factors (Fondon and Garner 2004;Verstrepen et al 2005). Adding or subtracting a single STR unit can have dramatic phenotypic effects, such as in the polyglutamine-encoding STR in the circadian clock gene ELF3 in Arabidopsis thaliana (Undurraga et al 2012). STR unit number can show striking nonlinear relationships with phenotype, which may in part be due to extensive epistatic interactions with other loci (Peixoto et al 1998;Butler et al 2007;Undurraga et al 2012).…”

“…Adding or subtracting a single STR unit can have dramatic phenotypic effects, such as in the polyglutamine-encoding STR in the circadian clock gene ELF3 in Arabidopsis thaliana (Undurraga et al 2012). STR unit number can show striking nonlinear relationships with phenotype, which may in part be due to extensive epistatic interactions with other loci (Peixoto et al 1998;Butler et al 2007;Undurraga et al 2012). Based on existing evidence, STR variation likely comprises an important component of the genotype-phenotype map (e.g., STRs are a viable explanation for some component of the "missing heritability" of genome-wide association studies) (Press et al 2014); yet due to technological difficulties in genotyping STRs, this component has remained largely undefined.…”

Quantitative Variation in Responses to Root Spatial Constraint within Arabidopsis thaliana

“…It is possible that ELF3 integrates root and shoot signals during competition to regulate the circadian clock and to elicit growth responses Hicks et al, 2001;Liu et al, 2001;Nieto et al, 2015). The Bay and Sha ELF3 alleles vary in the length of a poly-glutamine stretch and have an Ala (Bay) to Val (Sha) transition that leads to altered localization and posttranscriptional regulation via unknown mechanisms (Undurraga et al, 2012;Anwer et al, 2014). Future work will be required to determine how ELF3 mediates the flow of information between the root and shoot and to identify the signal that mediates this interaction.…”