Loss of flight in the Galapagos cormorant mirrors human skeletal ciliopathies

Abstract

Changes in the size and proportion of limbs and other structures have played a key role in the adaptive evolution of species. However, despite the ubiquity of these modifications, we have a very limited idea of how these changes occur on the genetic and molecular levels. To fill this gap, we studied a recent and extreme case of wing and pectoral skeleton size reduction leading to flightlessness in the Galapagos cormorant (Phalacrocorax harrisi). We sequenced and de novo assembled the genomes of four closely related cormorant species and applied a joint predictive and comparative genomics approach to find candidate variants. Here we report that function-altering variants in genes necessary for both the correct transcriptional regulation and function of the primary cilium contributed to the evolution of loss of flight in P. harrisi. Cilia are essential for Hedgehog signaling, and humans affected by skeletal ciliopathies suffer from premature arrest of bone growth, mirroring the skeletal features associated with loss of flight.