title: Dual-targeted proteins tend to be more evolutionarily conserved.
abstract: In eukaryotic cells, identical proteins can be located in more than a single subcellular compartment, a phenomenon termed dual targeting. We hypothesized that dual-targeted proteins should be more evolutionary conserved than exclusive mitochondrial proteins, due to separate selective pressures administered by the different compartments to maintain the functions associated with the protein sequences. We employed codon usage bias, propensity for gene loss, phylogenetic relationships, conservation analysis at the DNA level, and gene expression, to test our hypothesis. Our findings indicate that, indeed, dual-targeted proteins are significantly more conserved than their exclusively targeted counterparts. We then used this trait of gene conservation, together with previously identified traits of dual-targeted proteins (such as protein net charge and mitochondrial targeting sequence strength) to 1) create, for the first time (due to addition of conservation parameters), a tool for the prediction of dual-targeted mitochondrial proteins based on protein and mRNA sequences, and 2) show that molecular mechanisms involving one versus two translation products are not correlated with specific dual-targeting parameters. Finally, we discuss what evolutionary pressure maintains protein dual targeting in eukaryotes and deduce, as we initially hypothesized, that it is the discrete functions of these proteins in the different subcellular compartments, regardless of their dual-targeting mechanism.
authors: Department of Microbiology Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors: Irit
authors: I
authors: Kisslov
authors: Department of Microbiology Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel Department of Microbiology Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors: Adi
authors: A
authors: Naamati
authors: Department of Microbiology Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
authors: Nitzan
authors: N
authors: Shakarchy
authors: Department of Microbiology Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel CREATE-NUS-HUJ Cellular & Molecular Mechanisms of Inflammation Program, National University of Singapore, Singapore ophryp@ekmd.huji.ac.il.
authors: Ophry
authors: O
authors: Pines
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D008928:Mitochondria / Q000378:metabolism*; D008957:Models, Genetic; D010802:Phylogeny; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins
keywords: dual targeting; mitochondrial import; protein conservation