Abstract
The availability of whole genome assemblies from evolutionarily distant species and iterative search algorithms has boosted ortholog analyses. However, orthology per se is not a sufficient predictor of a specific function. In a recent study, we have combined bioinformatic analysis and biochemistry to study the evolution of the multi-component SMN (Survival Motor Neuron)-complex. This macromolecular machinery performs essential steps during the assembly of spliceosomal UsnRNPs. By orthology, many factors constituting the SMN-complex in humans developed early in evolution. Some were secondarily lost in Drosophila. Compositional investigation of the Drosophila SMN-complex by biochemistry revealed the absence of two predicted orthologs although the complex was functional. Their bioinformatical re-assessment showed rapid sequence divergence indicating loss of evolutionary pressure in Drosophila. As a tool to better understand the function of individual proteins in multimeric molecular machineries, we therefore advocate iterative combination of bioinformatics with biochemical or functional assessment.
