Natural variation in stochastic photoreceptor specification and color preference in Drosophila.

Caitlin Anderson,Elijah Roberts,Daniel Vasiliauskas,Benjamin Mormann,Cyrus Zhou,Alan Bergland,Haziq Siddiqi,Robert J Johnston,James Taylor,Annie Cho,Cameron M Avelis,Peter Deford,India Reiss

doi:10.7554/elife.29593

Abstract

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic on/off expression of the transcription factor Spineless (Ss). In a genome-wide association study, we identified a naturally occurring insertion in a regulatory DNA element in ss 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 expression, setting the ratio of alternative fates and ultimately determining color preference.

Highlights

Organisms require a diverse repertoire of sensory receptor neurons to perceive a range of stimuli in their environments
To determine the mechanism controlling the ratio of stochastic on/off Ss expression, we analyzed the variation in 203 naturally-derived lines collected from Raleigh, North Carolina (Drosophila Genetic Reference Panel (DGRP)) (Mackay et al, 2012)
We evaluated Rh4 and Rh3 expression, as they faithfully report Ss expression in R7s (i.e. SsON = Rh4; SsOFF = Rh3) (Figure 1A) (Thanawala et al, 2013; Johnston and Desplan, 2014)

Summary

Introduction

Organisms require a diverse repertoire of sensory receptor neurons to perceive a range of stimuli in their environments. We performed a genome-wide association study (GWAS) and identified a single base pair insertion that increases the affinity of a DNA binding site for a transcriptional repressor, significantly reducing the SsON/SsOFF ratio. This genetic variant changes the proportion of photoreceptor subtypes and alters the innate color preference of flies. Using a Ss antibody, we examined Ss expression directly and found that flies homozygous for CRISPR sin alleles displayed a significant decrease in the proportion of SsON R7s (Figure 1—figure supplement 2A–B and E). % reads of total bits bits sin neighboring sequence wild type ttcgACGCCCACACACgttg sin ttcgACGCCCACACCAcgtt predicted Klumpfuss/Klu binding motif

C T TC G AC GG A

C Chigh Klu levels

Discussion

Materials and methods

Funding Funder National Eye Institute