The genetic toolkit for tetrapod development and evolution

Abstract

The developmental toolkit (genetic toolkit for development) is a group of highly conserved genes that play crucial roles in developmental patterning and phenotypic evolution. Embryonic expression patterns of toolkit genes influence cell behaviour, and thereby shape the adult phenotype. In addition, toolkit genes play a role in regeneration, cancer and ageing. Despite their biological importance, there is no definitive list of toolkit genes. Our aim here is to compile such a list. We first searched five databases for genes related to the development of the tetrapod limb, a wellresearched model of evolution and development. This yielded 1,825 genes. Toolkit genes typically show pleiotropy, whereby they are involved in the development of multiple organ systems. We therefore eliminated limb‐only genes by screening against the genomes of eight limbless tetrapods (snakes). We also added tetrapod orthologues of Drosophila patterning mutants from the Heidelberg screen. Manual curation removed non‐toolkit genes, and added missing ones. Our final list contains 484 toolkit genes — among them transcriptional regulators (58.8%), signaling molecules (17.8%) and transmembrane signal receptors (9.3%). The HOX and FOX families, together with the TGF‐β superfamily, were the most highly represented gene families. Our list of toolkit genes, representing 2–3% of protein‐coding genes in the tetrapod genome, is provisional. It represents an important step towards a deeper understanding of the evolution and development of animal morphology. Finally, we suggest that it can constitute an entirely new gene ontology class: ‘toolkit gene’.