TY - JOUR T1 - Natural variation in stochastic photoreceptor specification and color preference in <em>Drosophila</em> JF - bioRxiv DO - 10.1101/153445 SP - 153445 AU - Caitlin Anderson AU - India Reiss AU - Cyrus Zhou AU - Annie Cho AU - Haziq Siddiqi AU - Ben Mormann AU - Cameron M. Avelis AU - Alan Bergland AU - Elijah Roberts AU - James Taylor AU - Daniel Vasiliauskas AU - Robert J. Johnston, Jr. Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/21/153445.abstract N2 - Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. Here we investigated natural variation in the development and function of the color vision system of Drosophila. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic expression of the transcription factor Spineless (Ss). Individual R7s randomly choose between SsON or SsOFF fates at a ratio of 65:35, resulting in unique patterns but consistent proportions of cell types across genetically identical retinas. In a genome wide association study, we identified a naturally occurring insertion in a regulatory DNA element in the ss gene that lowers the ratio of SsON to SsOFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of SsON to SsOFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic on/off gene expression, setting the ratio of alternative cell fates and ultimately determining color preference. ER -