RT Journal Article SR Electronic T1 The common developmental genetic toolkit of bilaterian crown clades after a billion years of divergence JF bioRxiv FD Cold Spring Harbor Laboratory SP 041806 DO 10.1101/041806 A1 Andrea Krämer-Eis A1 Luca Ferretti A1 Philipp H. Schiffer A1 Peter Heger A1 Thomas Wiehe YR 2016 UL http://biorxiv.org/content/early/2016/03/19/041806.abstract AB Bilateria constitute a monophyletic group of organisms comprising about 99% of all living animals. Since their initial radiation about 540Mya they have evolved a plethora of traits and body forms allowing them to conquer almost any habitat on earth. There are only few truly uniting and shared morphological features retained across the phylum. Unsurprisingly, also the genetic toolkit of bilateria is highly diverged.In the light of this divergence we investigated if a set of Bilaterian-specific genes exists and, beyond this, if such genes are related with respect to function and expression patterns among organisms as distant as fly, worm and fish. Using a conservative pyramidal approach of orthology inference we first employed BLAST to extract a set of protein-coding genes which has orthologs in all major branches of Bilateria, but no homologs in non-Bilaterian species. To characterize the proteins with respect to function, we developed a new method for multi-species GO analysis and augmented it by a human-curated annotation based on an extensive literature search. Finally, we extracted characteristic developmental expression profiles for Bilateria from the detailed data available for three model organisms and we explored the relation between expression and function.We find 85 clusters of pan-bilaterian proteins. Although some of these proteins belong to common developmental processes, they cover a wide range of biological components, from transcription factors to metabolic enzymes. The 85 groups include myoD, an important regulator of mesodermal cell fate and muscle development, and prospero and several other factors involved in nervous system development. They reveal a so far unknown connection between bilaterian key innovations (mesoderm, complex nervous system) and the emergence of new genes in the ancestor of bilaterians. In addition, the majority of these genes tends to be highly expressed when the adult body plan is constructed. These observations are compatible with the idea that bilaterians are characterized by the unfolding of an additional developmental phase, namely the transition of the larva to morphologically distinct adults.Author Summary Bilateria represent by far the largest and morphologically most diverse clade of all extant animals. The bilaterian radiation dates back to the so-called Cambrian explosion of species. Although bilateria show a large variety of very distinct body plans, they are also characterized by several common developmental and morphological properties, upon which their monophyly is based. Here, we wanted to know whether these common phenotypic features may also have a common genetic basis, manifested by a set of bilaterian lineage-specific genes. To address this question we compared the proteomes of bilaterian and non-bilaterian species and extracted an initial set of a few hundred candidate proteins. Their underlying genes were further post-processed by means of orthology clustering, multi-species GO enrichment, expression analysis and extensive literature mining. This resulted in a set of 85 clusters of orthologous genes with roles in body morphology-, neuronal system-and muscle development, as well as in cell-cell signalling processes. These genes can be regarded as very promising candidates for further investigation of the genetic basis of a pan-bilaterian pheno-or morphotype and they should be highly interesting targets for functional studies in non-model organisms.