A catalogue of Bilaterian-specific genes – their function and expression profiles in early development
Authors: Krämer-Eis Andrea , Ferretti Luca , Schiffer Philipp H. , Heger Peter , Wiehe Thomas 
Published: March 2016

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 Drosophila, Caenorhabditis and Danio. Using a conservative pyramidal approach of orthology inference we collected a set of protein-coding genes which have orthologs in all major branches of Bilateria, but no homologs in non-bilaterian species. To characterize the proteins with respect to function, we employ a novel 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 extensive data available for three model organisms and we explored the relation between expression and function.

Among an initial set of several hundred candidates we identified 85 clusters of orthologous proteins which passed our filter criteria for bilaterian specificity. Although some of these proteins belong to common developmental processes, they cover a wide range of biological components, from transcription factors to metabolic enzymes. For instance, the clusters include myoD, an important regulator of mesodermal cell fate and muscle development, and prospero and several other factors involved in nervous system development. Our results reveal a so far unknown connection between morphological key innovations of bilateria, such as the mesoderm and a complex nervous system, and their genetic basis. Furthermore, we find typical expression profiles for these bilaterian specific genes, with the majority of them being highly expressed when the adult body plan is constructed. These observations are compatible with the idea that bilaterians are characterized by the unfolding of a new 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 traits, on which their monophyly is based. Here, we wanted to know whether these common phenotypic features may also have a shared and conserved genetic basis. 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 thorough set of genes with roles in body morphology-, neuronal system‐ and muscle development, as well as in cell-cell signalling processes. This gene catalogue can be regarded as blue-print of a common bilaterian pheno‐ or morphotype and should contain highly interesting targets for further functional studies in model and non-model organisms.