Natural variation in stochastic photoreceptor specification and color preference inDrosophila

Abstract

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.

Interdependent regulation of stereotyped and stochastic photoreceptor fates in the fly eye

“…Both Run and Sal are sufficient to activate Ss expression in other cell types, yet neither appears to regulate the frequency of Ss expression. The only known regulator of Ss expression frequency is Klumpfuss (Klu), a transcriptional repressor ( Anderson et al, 2017 ). It appears that activating inputs promote Ss in R7s and R8s, supported by the roles of Run and Sal and the presence of an enhancer within ss that drives expression in all R7s and R8s ( Johnston and Desplan, 2014 ; Johnston et al, 2011 ).…”

“…In the complementary ~35% of R7s where Ss is not expressed, R7s take on pale R7 (pR7) fate, marked by expression of Rh3 and absence of Rh4 ( Fig. 1B ) ( Anderson et al, 2017 ; Johnston and Desplan, 2014 ; Wernet et al, 2006 ). In yR7s, Ss activates Rh4 directly and represses Rh3 by activating the transcriptional repressor Defective Proventriculus (Dve) ( Fig.…”