When one plus one equals three: biochemistry and bioinformatics combine to answer complex questions.
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.
Kroiss
Matthias
M
Theodor-Boveri-Institute, Biocenter, Würzburg, Germany. Kroiss_M@klinik.uni-wuerzburg.de
Fischer
Utz
U
Schultz
Jörg
J
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
D029721:Drosophila Proteins; D017411:Ribonucleoproteins, Small Nuclear