RT Journal Article SR Electronic T1 Variation in a pleiotropic hub gene drives morphological evolution: Insights from interspecific differences in head shape and eye size in Drosophila JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.24.918011 DO 10.1101/2020.01.24.918011 A1 Buchberger, Elisa A1 Bilen, Anıl A1 Ayaz, Sanem A1 Salamanca, David A1 Matas de las Heras, Cristina A1 Niksic, Armin A1 Almudi, Isabel A1 Torres-Oliva, Montserrat A1 Casares, Fernando A1 Posnien, Nico YR 2020 UL http://biorxiv.org/content/early/2020/06/14/2020.01.24.918011.abstract AB Revealing the mechanisms underlying the breath-taking morphological diversity observed in nature is a major challenge in Biology. It has been established that recurrent mutations in hotspot genes cause the repeated evolution of rather simple morphological traits, such as body pigmentation or the gain and loss of structures. To date, however, it remains elusive whether hotspot genes contribute to natural variation in complex morphological traits, such as the size and shape of organs. Since natural variation in head morphology is pervasive in Drosophila, we studied the molecular and developmental basis of differences in compound eye size and head shape in two closely related Drosophila species. We show that differences in both traits are established late during head development and we applied comparative transcriptomics and chromatin accessibility data to identify the GATA transcription factor Pannier (Pnr) as central factor regulating these differences. Although the genetic manipulation of Pnr affected multiple aspects of dorsal head development, the effect of natural variation is restricted to a subset of the phenotypic space. We present data suggesting that this developmental constraint is caused by the co-evolution of expression of pnr and its co-factor u-shaped (ush). We propose that natural variation in highly connected developmental regulators with pleiotropic functions is a major driver for morphological evolution and we discuss implications on gene regulatory network evolution. In comparison to previous findings, our data strongly suggests that evolutionary hotspots do not contribute to the repeated evolution of eye size and head shape in Drosophila.Competing Interest StatementThe authors have declared no competing interest.