Fast co-evolution of sevenless and bride of sevenless in endopterygote insects.

Activation of Ras signaling by the receptor tyrosine kinase Sevenless plays important roles during retinal patterning and male germline development in Drosophila. Sevenless is orthologous to the vertebrate receptor tyrosine kinase c-ros. Remarkably, vertebrate ligands of c-Ros as well as non-Drosophila orthologs of the Sevenless ligand Bride of sevenless have remained elusive. Using newly available insect genome sequence information, we investigated the evolutionary conservation of the seven transmembrane domain protein gene bride of sevenless. Single orthologs were identified in the genomes of mosquito, flour beetle, and honeybee due to strong sequence conservation in the seven transmembrane domain. The extracellular region, however, is only detectably conserved within but not outside Diptera. Analysis of domain-specific substitution rates demonstrates correlated fast rates of evolutionary change in the extracellular domains of both bride of sevenless and sevenless. The rapid pace of sequence change explains why Sevenless ligands are difficult to detect by sequence similarity in distantly related phyla. Second, the conservation of bride of sevenless in flour beetle and honeybee raises the possibility of conserved Sevenless signaling controlled patterning processes in endopterygote insects.