RUI: There is more to the Hox code than you thought - the role of the "Hox fin/limb building toolkit" genes in the evolution of vertebrate diversity

San Francisco State University, San Francisco CA

Investigators

Abstract

One of the primary goals of Evolutionary Developmental Biology is to understand the genetic basis of morphological evolution. While there is intense interest in cataloging and conserving diversity in nature, we are only beginning to understand the mechanisms responsible for generating biodiversity. Fins and limbs are homologous structures that are patterned by a shared genetic repertoire of HoxA/D expression, which has been referred to as the 'Hox fin/limb building toolkit'. A unique expression pattern is associated with the most famous example of a novel limb modification that specifies digit identity and the origin of the thumb in the human hand. The pattern also occurs in fishes and sharks, indicating that it arose in the common ancestor of jawed vertebrates. Recent evidence indicates that the Hox code is more complex than previously recognized, yet few derived morphologies have been evaluated. This project examines the role of Hox genes in the evolution and development of novel fin/limb modifications in three divergent lineages that exhibit unique body plan features, and for which the ecological or physiological significance is understood. This research engages undergraduates in using genomic tools to answer newly tractable questions, and is based at a public state university that serves a large undergraduate population with a high proportion of underrepresented minorities. The focal taxa (sharks, manta rays, paddlefish and surfperches) are highly charismatic and command intense interest in the public eye. The PI has a track record of involving undergraduates in research, professional presentations, and publication, and will develop educational materials to engage the general public in understanding the genetic underpinnings of the evolution of diversity, including fin and limb modifications that share deep homology with our own hands and feet, while serving the NSF's mission of connecting research, education and public outreach. Vertebrates exhibit a remarkable array of fin and limb modifications that are clear homologs of human appendages, yet the genetic underpinnings of most have not been characterized. Their variety forms the basis for the observed morphological diversity in vertebrates, and their novelty provides a unique opportunity for elucidating general principles of morphological evolution. The overarching goal of this research is to evaluate the modularity and plasticity of the Hox fin/limb-building program in the evolution of morphological diversity in vertebrates by addressing the following questions: - Do claspers or cephalic lobes represent independent sets of paired appendages in modern cartilaginous fishes that are patterned by the Hox fin/limb pathway genes? - Are novel deployments of the Hox fin/limb pathway genes associated with morphological diversity in medial fin structures such as the genital protuberance in surfperch anal fin, or the elongated caudal fin in paddlefish? This research will employ a functional genomic screen composed of multiple approaches including RNASeq, in situ hybridization, functional assays, and evaluation of conserved/novel regulatory sequences for the Hox fin/limb toolkit genes that are known to pattern fins/limbs in model taxa.