title: Mitochondrial genomes are retained by selective constraints on protein targeting.
abstract: Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome.
authors.affiliation: Department of Molecular Evolution, Cell, and Molecular Biology, Uppsala University, 752 36 Uppsala, Sweden;
authors.forename: Patrik
authors.initials: P
authors.lastname: Björkholm
authors.affiliation: Department of Molecular Evolution, Cell, and Molecular Biology, Uppsala University, 752 36 Uppsala, Sweden;
authors.forename: Ajith
authors.initials: A
authors.lastname: Harish
authors.affiliation: Department of Molecular Evolution, Cell, and Molecular Biology, Uppsala University, 752 36 Uppsala, Sweden;
authors.forename: Erik
authors.initials: E
authors.lastname: Hagström
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Ernst
authors.affiliation: Department of Molecular Evolution, Cell, and Molecular Biology, Uppsala University, 752 36 Uppsala, Sweden; Siv.Andersson@icm.uu.se.
authors.forename: Siv G E
authors.initials: SG
authors.lastname: Andersson
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics; D060365:Chloroplast Proteins / Q000378:metabolism; D019295:Computational Biology; D045303:Cytochromes b / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D054629:Genome, Mitochondrial / Q000235:genetics*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010802:Phylogeny; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D018271:Signal Recognition Particle / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D060365:Chloroplast Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018271:Signal Recognition Particle; D045303:Cytochromes b; C412204:ATP synthase subunit 6; D025261:Mitochondrial Proton-Translocating ATPases
keywords: endoplasmatic reticulum; evolution; mitochondria; protein domain; signal recognition particle