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Joseph McGirr (UNC-Chapel Hill)

Editing naturally occurring genetic variants affecting craniofacial development

Graduate Student Award in Innovative Evolutionary Medicine

When species evolve the ability to consume a new food source, they often develop unique traits that are specially adapted to their new diet. Rapid diversification on a small island in the Caribbean gave rise to two species of Cyprinodon pupfish that have adopted very different feeding strategies. C. desquamator evolved very large jaws capable of tearing scales off other pupfishes; whereas C. brontotheroides evolved smaller jaws and a protruding nasal region that help it to crush hard-shelled prey. While these species look and behave very differently, they have recently evolved from a common ancestor within the last 10,000 years and share 99.988% of their genomes. My work focuses on the 0.012% difference to understand how a small amount of genetic change led to such dramatic changes in craniofacial traits. As jawed vertebrates, we humans share many of the same gene pathways that control jaw development in Cyprinodon pupfishes. Excitingly, one of the genes I found associated with larger jaws (znf664) seems to activate a similar network of genes in pupfishes and human cell lines. I also identified a gene associated with smaller jaws (dlx6) that is essential for lower jaw development and responsible for a wide range of craniofacial defects in vertebrates. Uncovering genetic variation controlling the expression of these candidate genes will have a significant impact on our understanding of risk factors associated with congenital craniofacial abnormalities, which will support efforts to reduce the severity and prevalence of these conditions.

Publications:

McGirr JA and Martin CH. (2019). Hybrid misregulation in multiple developing tissues within a recent adaptive radiation of Cyprinodon pupfishesPLoS One.

McGirr JA and Martin CH. (2020). Ecological divergence in sympatry causes gene misexpression in hybridsMolecular Ecology.

McGirr JA and Martin CH. (2020). Few fixed variants between trophic specialist pupfish species reveal candidate cis-regulatory alleles underlying rapid craniofacial divergenceMolecular Biology and Evolution.