The effects of weak genetic perturbations on the transcriptome of the wing imaginal disc and its association with wing shape in Drosophila melanogaster.

A major objective of genomics is to elucidate the mapping between genotypic and phenotypic space as a step toward understanding how small changes in gene function can lead to elaborate phenotypic changes. One approach that has been utilized is to examine overall patterns of covariation between phenotypic variables of interest, such as morphology, physiology, and behavior, and underlying aspects of gene activity, in particular transcript abundance on a genome-wide scale. Numerous studies have demonstrated that such patterns of covariation occur, although these are often between samples with large numbers of unknown genetic differences (different strains or even species) or perturbations of large effect (sexual dimorphism or strong loss-of-function mutations) that may represent physiological changes outside of the normal experiences of the organism. We used weak mutational perturbations in genes affecting wing development in Drosophila melanogaster that influence wing shape relative to a co-isogenic wild type. We profiled transcription of 1150 genes expressed during wing development in 27 heterozygous mutants, as well as their co-isogenic wild type and one additional wild-type strain. Despite finding clear evidence of expression differences between mutants and wild type, transcriptional profiles did not covary strongly with shape, suggesting that information from transcriptional profiling may not generally be predictive of final phenotype. We discuss these results in the light of possible attractor states of gene expression and how this would affect interpretation of covariation between transcriptional profiles and other phenotypes.