RT Journal Article SR Electronic T1 Novel approach to quantitative spatial gene expression uncovers genetic stochasticity in the developing Drosophila eye JF bioRxiv FD Cold Spring Harbor Laboratory SP 175711 DO 10.1101/175711 A1 Sammi Ali A1 Sarah A. Signor A1 Konstantin Kozlov A1 Sergey V. Nuzhdin YR 2018 UL http://biorxiv.org/content/early/2018/03/08/175711.abstract AB Robustness in development allows for the accumulation of neutral genetically based variation in expression, and here will be termed ‘genetic stochasticity‘. This largely neutral variation is potentially important for both evolution and complex disease phenotypes. However, it has generally only been investigated as variation exhibited in the response to large genetic perturbations. In addition, work on variation in gene expression has similarly generally been limited to being spatial, or quantitative, but because of technical restrictions not both. Here we bridge these gaps by investigating replicated quantitative spatial gene expression using rigorous statistical models, in different genotypes, sexes, and species (Drosophila melanogaster and D. simulans). Using this type of quantitative approach with developmental data allows for effective comparison among conditions, including health versus disease. We apply this approach to the morphogenetic furrow, a wave of differentiation that sweeps across the developing eye disc. Within the morphogenetic furrow, we focus on four conserved morphogens, hairy, atonal, hedgehog, and Delta. Hybridization chain reaction quantitatively measures spatial gene expression, co-staining for all four genes simultaneously and with minimal effort. We find considerable variation in the spatial expression pattern of these genes in the eye between species, genotypes, and sexes. We also find that there has been evolution of the regulatory relationship between these genes. Lastly, we show that the spatial interrelationships of these genes evolved between species in the morphogenetic furrow. This is essentially the first ‘population genetics of development’ as we are able to evaluate wild type differences in spatial and quantitative gene expression at the level of genotype, species and sex.