Anole Lizard Genomes: A Window into Amniote Regeneration and Understanding the Genetic Etiology of Human Musculoskeletal Disorders

Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacement. These regenerated tails contain newly formed hyaline cartilage, spinal cord, skeletal muscle, and skin. Progress in studying the cellular and molecular mechanisms of lizard regeneration has been limited by lack of genomic resources. With the release of the genome of the green anole, Anolis carolinensis, and our deep transcriptome based annotation of this genome (Eckalbar et al., 2013), we have a unique opportunity to identify the cells and pathways activated in lizard regeneration. We have quantified the transcriptomic profile along the proximal to distal axis of the regenerating tail, compared to adult tissues and stem cell rich tissues. Gene Ontology groups with elevated expression at the growing tail tip include members of key developmental regulatory pathways, including the MAPK signaling and Wnt/beta-catenin pathways, response to wounding and inflammation, thyroid hormone generation, and skeletal system development. GO groups elevated in the proximal differentiating tail include muscle contraction, regulation of ATPase activity, and biological adhesion. These studies have identified components of a genetic program for regeneration in the lizard that includes both developmental and adult repair mechanisms, applicable for future regenerative medical therapies.

Anole lizards are also a spectacular example of adaptive radiation in vertebrates, with musculoskeletal adaptations for specific ecological niches. In order to identify the coding and cis-regulatory changes that drive these adaptations, we have completed whole genome sequencing of three neotropical anole species: the grass anole (A. auratus), the Central American giant anole (A. frenatus), and the slender anole (A. apletophallus). Functional anatomical and histological studies are being performed to quantify the tail and hindlimb muscle groups of these species compared to A. carolinensis. We expect that these anatomical data combined with comparative analysis of coding and regulatory sequences will allow us to identify the divergent alleles associated with changes in anole musculoskeletal development. These studies will help to identify conserved amniote regulatory networks and enhancer sequences that are relevant to understanding the etiology of human musculoskeletal disorders.

Acknowledgements: NIH grants NCRR/ORIP R21RR031305 and NIAMS R21AR064935, grant 1113 from the Arizona Biomedical Research Commission, and funding from Arizona State University and the Smithsonian Tropical Research Institute.