title: When one plus one equals three: biochemistry and bioinformatics combine to answer complex questions.
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.
authors.affiliation: Theodor-Boveri-Institute, Biocenter, Würzburg, Germany. Kroiss_M@klinik.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Kroiss
authors.forename: Utz
authors.initials: U
authors.lastname: Fischer
authors.forename: Jörg
authors.initials: J
authors.lastname: Schultz
mesh_terms: D000818:Animals; D001669:Biochemical Phenomena; D019295:Computational Biology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012326:RNA Splicing; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D017411:Ribonucleoproteins, Small Nuclear