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Abstract

The genetic basis of morphological variation has been a long lasting question in biology both within and between species. We are using a forward genetic approach in zebrafish to investigate this question. As part of a large-scale screen, we isolated a mutant, spiegeldanio (spd), which displayed a scale-loss phenotype similar to variation seen in other fish species. We positionally cloned spd and found a missense mutation in the kinase domain of the fibroblast growth factor receptor 1 (fgfr1) gene. The specificity of fgf signaling in vertebrate development is thought to arise from genome duplications and expansion of paralogues with unique developmental functions. Consistent with this, we find a second, uncharacterized, paralogue of fgfr1 (fgfr1b) in zebrafish confirming the duplication of this gene in teleosts. Due to the phenotypic similarity between spd and the mirror carp (C. Carpio), we cloned fgfr1a from the carp. We show that the mirror carp phenotype is due to mutations in the kinase domain of one fgfr1a paralogue. We next sought a case of naturally occurring scale-loss. The Phoxinellus genus is a naturally occurring species in which scale-loss is a defining, derived trait for the genus. We found a consistent amino acid change in fgfr1a in two Phoxinellus species compared to the scaled outgroup, Telestes. We are testing the causation of this change by genetic sweep analysis and functional rescue in zebrafish spd mutants. These two cases support the utility of using forward genetics to identify genes involved in evolutionary change.