Meeting Abstract
Evo-devo theory posits that variation in cis-regulatory enhancers, which regulate the spatiotemporal pattern of gene expression, is a primary mechanism for morphological evolution. However, identifying relevant enhancers and characterizing their in vivo function remains a challenge. Recent studies in model organisms have experimentally identified >75000 enhancers active during facial, cartilage, and/or bone development. In order to identify which of these enhancers may mediate the unparalleled craniofacial variation that is a hallmark of the adaptive radiation of cichlid fishes, we utilized a bioinformatic approach. Specifically, we mapped enhancers experimentally identified in mammals to the tilapia genome, and cross reference these to both craniofacial QTL and genomic regions that exhibit high levels of genotypic divergence (i.e. high FST) among phenotypically divergent cichlid species. This approach prioritizes enhancers in an efficient and unbiased way from ten of thousands to dozens for functional assays. Using this method, we prioritized a putative sox9b enhancer that lies within QTLs for both lower jaw width and length and has fixed mutations in species that vary in jaw phenotypes. Using the CRISPR system in zebrafish, we show that genetic variation in the sox9b enhancer results in the highly specific loss of ceratobranchial cartilages as well as phenotypic variation in the lower jaw that mimics natural variation in jaw shape between cichlid species. We suggest that the bioinformatic integration of QTL and population genomic data from evolutionary models like cichlids with enhancer data from model organisms offers a powerful approach to both prioritize and functionally evaluate enhancers that may mediate morphological evolution.
