Peptides encoded by short ORFs control development and define a new eukaryotic gene family

Despite recent advances in developmental biology and in genomics, key questions remain regarding the organisation of cells into embryos. One possibility is that novel types of genes might await discovery and could provide some of the answers. Genome annotation depends strongly on comparison with previously known gene sequences, and so genes having previously uncharacterised structure and function can be missed. Here we present the characterisation of tarsal-less, a new such type of gene. Tarsal-less has two unusual features: first, it contains more than one coding unit, a structure more similar to some bacterial genes. Second, it codes for small peptides rather than proteins, and in fact these peptides represent the smallest gene products known to date. Functional analysis of this gene in the fruitfly Drosophila shows that it has important functions throughout development, including tissue morphogenesis and pattern formation. We identify genes similar to tarsal-less in other species, and thus define a tarsal-less-related gene family. We expect that a combination of bioinformatic and functional methods, such as the ones we use in this study, will identify and characterize more genes of this type. Potentially, thousands of such new genes may exist.