The ability of populations to continually respond to directional selection even after many generations instead of reaching response plateaus suggests the presence of mechanisms for rapidly generating novel adaptive variation within organismal genomes. The contributions of cis regulation are now being widely studied. This study details the contributions of one such mechanism capable of generating adaptive genetic variation through transcribed microsatellite mutation. Microsatellites are abundant in eukaryotic genomes, exhibit one of the highest known mutation rates; and mutations involve indels that are reversible. These features make them excellent candidates for generating variation in populations. This study explores the functional roles of transcribed microsatellites in Helianthus annuus (common sunflower). More specifically, I explored the role of microsatellites as agents of rapid change that act as “tuning knobs” of phenotypic variation by influencing gene expression in a stepwise manner by expansions and contractions of the microsatellite tract. A bioinformatic study suggests that selection has favored expansion and maintenance of transcriptomic microsatellites. This inference is based on the non-random distribution of microsatellites, prevalence of motifs associated with gene regulation in untranslated regions, and the enrichment of microsatellites in Gene Ontologies representing plant response to stress and stimulus. A population genetics study provides support for selection on these transcribed microsatellites when compared to anonymous microsatellites that were assumed to evolve neutrally. The natural populations utilized in this study show greater similarity in allele frequencies, mean length, and variance in lengths at the transcribed microsatellites relative to that observed at anonymous microsatellite loci. This finding is indicative of balancing selection, and provides evidence that allele lengths are under selection. This finding provides support for the tuning knob hypothesis. The findings of a functional genomic study with regard to the tuning knob hypothesis are ambiguous. No correlation between allele lengths and gene expression was detected at any of three loci investigated. However, the loci utilized exhibited narrow ranges in length. The tuning knob hypothesis implies that similar allele lengths are likely to exhibit similar gene expression levels. Hence, variation in the populations studied may be tracking the optimal gene expression levels.