02090nas a2200169   4500008004100000245011600041210006900157300000900226490000600235520123000241653007701471653008501548653014401633100001801777700001901795856010601814       2007                        eng d00aFrom endosymbiont to host-controlled organelle: the hijacking of mitochondrial protein synthesis and metabolism0 aFrom endosymbiont to hostcontrolled organelle the hijacking of m  ae2190 v33 aMitochondria are eukaryotic organelles that originated from the endosymbiosis of an alpha-proteobacterium. To gain insight into the evolution of the mitochondrial proteome as it proceeded through the transition from a free-living cell to a specialized organelle, we compared a reconstructed ancestral proteome of the mitochondrion with the proteomes of alpha-proteobacteria as well as with the mitochondrial proteomes in yeast and man. Overall, there has been a large turnover of the mitochondrial proteome during the evolution of mitochondria. Early in the evolution of the mitochondrion, proteins involved in cell envelope synthesis have virtually disappeared, whereas proteins involved in replication, transcription, cell division, transport, regulation, and signal transduction have been replaced by eukaryotic proteins. More than half of what remains from the mitochondrial ancestor in modern mitochondria corresponds to translation, including post-translational modifications, and to metabolic pathways that are directly, or indirectly, involved in energy conversion. Altogether, the results indicate that the eukaryotic host has hijacked the proto-mitochondrion, taking control of its protein synthesis and metabolism.10aComputer Simulation DNA Mutational Analysis/methods Evolution *Evolution10aGenetic Organelles/physiology Protein Biosynthesis/*genetics Symbiosis/*genetics10aMolecular Fungal Proteins/*physiology Genetic Variation/genetics Humans Mitochondria/*physiology Mitochondrial Proteins/*physiology *Models1 aGabaldón, T.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1798326500409nas a2200109   4500008004100000245004200041210004200083260002400125100001800149700001900167856011300186       2007                        eng d00aReconstruction of ancestral proteomes0 aReconstruction of ancestral proteomes  aOxfordbD. Liberles1 aGabaldón, T.1 aHuynen, M., A.  uhttp://www.us.oup.com/us/catalog/general/subject/LifeSciences/EvolutionaryBiology/?view=usa&ci=978019929918802737nas a2200181   4500008004100000245005300041210005300094300000600147490000600153520218900159100001802348700001302366700002102379700001602400700001402416700001902430856010602449       2006                        eng d00aOrigin and evolution of the peroxisomal proteome0 aOrigin and evolution of the peroxisomal proteome  a80 v13 aBACKGROUND: Peroxisomes are ubiquitous eukaryotic organelles involved in various oxidative reactions. Their enzymatic content varies between species, but the presence of common protein import and organelle biogenesis systems support a single evolutionary origin. The precise scenario for this origin remains however to be established. The ability of peroxisomes to divide and import proteins post-translationally, just like mitochondria and chloroplasts, supports an endosymbiotic origin. However, this view has been challenged by recent discoveries that mutant, peroxisome-less cells restore peroxisomes upon introduction of the wild-type gene, and that peroxisomes are formed from the Endoplasmic Reticulum. The lack of a peroxisomal genome precludes the use of classical analyses, as those performed with mitochondria or chloroplasts, to settle the debate. We therefore conducted large-scale phylogenetic analyses of the yeast and rat peroxisomal proteomes. RESULTS : Our results show that most peroxisomal proteins (39-58%) are of eukaryotic origin, comprising all proteins involved in organelle biogenesis or maintenance. A significant fraction (13-18%), consisting mainly of enzymes, has an alpha-proteobacterial origin and appears to be the result of the recruitment of proteins originally targeted to mitochondria. Consistent with the findings that peroxisomes are formed in the Endoplasmic Reticulum, we find that the most universally conserved Peroxisome biogenesis and maintenance proteins are homologous to proteins from the Endoplasmic Reticulum Assisted Decay pathway. CONCLUSION: Altogether our results indicate that the peroxisome does not have an endosymbiotic origin and that its proteins were recruited from pools existing within the primitive eukaryote. Moreover the reconstruction of primitive peroxisomal proteomes suggests that ontogenetically as well as phylogenetically, peroxisomes stem from the Endoplasmic Reticulum. REVIEWERS: This article was reviewed by Arcady Mushegian, Gaspar Jekely and John Logsdon. OPEN PEER REVIEW: Reviewed by Arcady Mushegian, Gaspar Jekely and John Logsdon. For the full reviews, please go to the Reviewers’ comments section.1 aGabaldón, T.1 aSnel, B.1 avan Zimmeren, F.1 aHemrika, W.1 aTabak, H.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1655631400503nas a2200133   4500008004100000022001600041245010000057210006900157260003700226100001900263700001300282700001700295856005700312       2006                        eng d  a0-387-3452700aReliable and specific protein function prediction by combining homology with genomic(s) context0 aReliable and specific protein function prediction by combining h  bF. Eisenhaber, Landes Bioscience1 aHuynen, M., A.1 aSnel, B.1 aT, Gabaldón  uhttp://www.landesbioscience.com/iu/output.php?id=47902676nas a2200313   4500008004100000245005400041210005100095300000900146490000800155520141200163653011201575653025901687100001401946700002101960700002601981700002102007700001502028700001802043700002102061700003202082700002002114700002602134700002002160700001802180700001702198700001902215700002202234856010602256       2005                        eng d00aAn anaerobic mitochondrion that produces hydrogen0 aanaerobic mitochondrion that produces hydrogen  a74-90 v4343 aHydrogenosomes are organelles that produce ATP and hydrogen, and are found in various unrelated eukaryotes, such as anaerobic flagellates, chytridiomycete fungi and ciliates. Although all of these organelles generate hydrogen, the hydrogenosomes from these organisms are structurally and metabolically quite different, just like mitochondria where large differences also exist. These differences have led to a continuing debate about the evolutionary origin of hydrogenosomes. Here we show that the hydrogenosomes of the anaerobic ciliate Nyctotherus ovalis, which thrives in the hindgut of cockroaches, have retained a rudimentary genome encoding components of a mitochondrial electron transport chain. Phylogenetic analyses reveal that those proteins cluster with their homologues from aerobic ciliates. In addition, several nucleus-encoded components of the mitochondrial proteome, such as pyruvate dehydrogenase and complex II, were identified. The N. ovalis hydrogenosome is sensitive to inhibitors of mitochondrial complex I and produces succinate as a major metabolic end product–biochemical traits typical of anaerobic mitochondria. The production of hydrogen, together with the presence of a genome encoding respiratory chain components, and biochemical features characteristic of anaerobic mitochondria, identify the N. ovalis organelle as a missing link between mitochondria and hydrogenosomes.10a*Anaerobiosis Animals Ciliophora/*cytology/genetics/*metabolism/ultrastructure Cockroaches/parasitology DNA10aMitochondrial/genetics Electron Transport Electron Transport Complex I/antagonists & inhibitors/metabolism Genome Glucose/metabolism Hydrogen/*metabolism Mitochondria/enzymology/genetics/*metabolism/ultrastructure Molecular Sequence Data Open Reading Fra1 aBoxma, B.1 ade Graaf, R., M.1 avan der Staay, G., W.1 avan Alen, T., A.1 aRicard, G.1 aGabaldón, T.1 avan Hoek, A., H.1 avan der Staay, S., Y. Moon-1 aKoopman, W., J.1 avan Hellemond, J., J.1 aTielens, A., G.1 aFriedrich, T.1 aVeenhuis, M.1 aHuynen, M., A.1 aHackstein, J., H.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1574430201615nas a2200181   4500008004100000245012100041210006900162300001000231490000800241520089300249653003301142653008301175100001901258700001901277700001801296700001301314856010601327       2005                        eng d00aCombining data from genomes, Y2H and 3D structure indicates that BolA is a reductase interacting with a glutaredoxin0 aCombining data from genomes Y2H and 3D structure indicates that   a591-60 v5793 aGenomes, functional genomics data and 3D structure reflect different aspects of protein function. Here, we combine these data to predict that BolA, a widely distributed protein family with unknown function, is a reductase that interacts with a glutaredoxin. Comparisons at the 3D structure level as well as at the sequence profile level indicate homology between BolA and OsmC, an enzyme that reduces organic peroxides. Complementary to this, comparative analyses of genomes and genomics data provide strong evidence of an interaction between BolA and the mono-thiol glutaredoxin family. The interaction between BolA and a mono-thiol glutaredoxin is of particular interest because BolA does not, in contrast to its homolog OsmC, have evolutionarily conserved cysteines to provide it with reducing equivalents. We propose that BolA uses the mono-thiol glutaredoxin as the source for these.10a*Genome Glutaredoxins Models10aMolecular Oxidoreductases/chemistry/*metabolism Phylogeny Protein Conformation1 aHuynen, M., A.1 aSpronk, C., A.1 aGabaldón, T.1 aSnel, B.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1567081301787nas a2200181   4500008004100000245012500041210006900166300001300235490001500248520091200263653004401175653003901219653014701258653005701405100001801462700001901480856010601499       2005                        eng d00aLineage-specific gene loss following mitochondrial endosymbiosis and its potential for function prediction in eukaryotes0 aLineagespecific gene loss following mitochondrial endosymbiosis   aii144-500 v21 Suppl 23 aMOTIVATION: The endosymbiotic origin of mitochondria has resulted in a massive horizontal transfer of genetic material from an alpha-proteobacterium to the early eukaryotes. Using large-scale phylogenetic analysis we have previously identified 630 orthologous groups of proteins derived from this event. Here we show that this proto-mitochondrial protein set has undergone extensive lineage-specific gene loss in the eukaryotes, with an average of three losses per orthologous group in a phylogeny of nine species. This gene loss has resulted in a high variability of the alphaproteobacterial-derived gene content of present-day eukaryotic genomes that might reflect functional adaptation to different environments. Proteins functioning in the same biochemical pathway tend to have a similar history of gene loss events, and we use this property to predict functional interactions among proteins in our set.10aAnimals Chromosome Mapping/*methods DNA10aMitochondrial/*genetics *Evolution10aMolecular *Gene Deletion Genetic Variation/genetics Humans Linkage Disequilibrium/*genetics Mitochondrial Proteins/*genetics Sequence Homology10aNucleic Acid Species Specificity Symbiosis/*genetics1 aGabaldón, T.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1620409402633nas a2200181   4500008004100000245011500041210006900156300001100225490000800236520169000244653015501934653019202089653001202281100001802293700001502311700001902326856010602345       2005                        eng d00aTracing the evolution of a large protein complex in the eukaryotes, NADH:ubiquinone oxidoreductase (Complex I)0 aTracing the evolution of a large protein complex in the eukaryot  a857-700 v3483 aThe increasing availability of sequenced genomes enables the reconstruction of the evolutionary history of large protein complexes. Here, we trace the evolution of NADH:ubiquinone oxidoreductase (Complex I), which has increased in size, by so-called supernumary subunits, from 14 subunits in the bacteria to 30 in the plants and algae, 37 in the fungi and 46 in the mammals. Using a combination of pair-wise and profile-based sequence comparisons at the levels of proteins and the DNA of the sequenced eukaryotic genomes, combined with phylogenetic analyses to establish orthology relationships, we were able to (1) trace the origin of six of the supernumerary subunits to the alpha-proteobacterial ancestor of the mitochondria, (2) detect previously unidentified homology relations between subunits from fungi and mammals, (3) detect previously unidentified subunits in the genomes of several species and (4) document several cases of gene duplications among supernumerary subunits in the eukaryotes. One of these, a duplication of N7BM (B17.2), is particularly interesting as it has been lost from genomes that have also lost Complex I proteins, making it a candidate for a Complex I interacting protein. A parsimonious reconstruction of eukaryotic Complex I evolution shows an initial increase in size that predates the separation of plants, fungi and metazoa, followed by a gradual adding and incidental losses of subunits in the various evolutionary lineages. This evolutionary scenario is in contrast to that for Complex I in the prokaryotes, for which the combination of several separate, and previously independently functioning modules into a single complex has been proposed.10aAmino Acid Sequence Animals Computational Biology Electron Transport Complex I/*chemistry/*genetics/metabolism Eukaryotic Cells/*enzymology *Evolution10aMolecular Humans Molecular Sequence Data Photosynthesis Phylogeny Plastids/enzymology Protein Binding Protein Subunits/chemistry/genetics/metabolism Sequence Alignment Structural Homology10aProtein1 aGabaldón, T.1 aRainey, D.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1584301801857nas a2200169   4500008004100000245008800041210006900129300001200198490000800210520119800218653001501416653010001431100001901531700001801550700001301568856010601581       2005                        eng d00aVariation and evolution of biomolecular systems: searching for functional relevance0 aVariation and evolution of biomolecular systems searching for fu  a1839-450 v5793 aThe availability of genome sequences and functional genomics data from multiple species enables us to compare the composition of biomolecular systems like biochemical pathways and protein complexes between species. Here, we review small- and large-scale, "genomics-based" approaches to biomolecular systems variation. In general, caution is required when comparing the results of bioinformatics analyses of genomes or of functional genomics data between species. Limitations to the sensitivity of sequence analysis tools and the noisy nature of genomics data tend to lead to systematic overestimates of the amount of variation. Nevertheless, the results from detailed manual analyses, and of large-scale analyses that filter out systematic biases, point to a large amount of variation in the composition of biomolecular systems. Such observations challenge our understanding of the function of the systems and their individual components and can potentially facilitate the identification and functional characterization of sub-systems within a system. Mapping the inter-species variation of complex biomolecular systems on a phylogenetic species tree allows one to reconstruct their evolution.10a*Evolution10aMolecular Genetic Variation Multiprotein Complexes/*genetics Phylogeny Protein Binding/genetics1 aHuynen, M., A.1 aGabaldón, T.1 aSnel, B.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1576356102058nas a2200169   4500008004100000245006600041210006600107300001100173490000700184520119200191653019701383653012101580653004401701100001801745700001901763856010601782       2004                        eng d00aPrediction of protein function and pathways in the genome era0 aPrediction of protein function and pathways in the genome era  a930-440 v613 aThe growing number of completely sequenced genomes adds new dimensions to the use of sequence analysis to predict protein function. Compared with the classical knowledge transfer from one protein to a similar sequence (homology-based function prediction), knowledge about the corresponding genes in other genomes (orthology-based function prediction) provides more specific information about the protein’s function, while the analysis of the sequence in its genomic context (context-based function prediction) provides information about its functional context. Whereas homology-based methods predict the molecular function of a protein, genomic context methods predict the biological process in which it plays a role. These complementary approaches can be combined to elucidate complete functional networks and biochemical pathways from the genome sequence of an organism. Here we review recent advances in the field of genomic-context based methods of protein function prediction. Techniques are highlighted with examples, including an analysis that combines information from genomic-context with homology to predict a role of the RNase L inhibitor in the maturation of ribosomal RNA.10aATP-Binding Cassette Transporters/genetics/metabolism Amino Acid Sequence Animals Artificial Gene Fusion Base Sequence Chaperonins/genetics/metabolism Chromosomes/genetics/metabolism Evolution10aMolecular *Genome Genomics Humans Molecular Sequence Data Phylogeny *Proteins/classification/genetics/metabolism RNA10aRibosomal/metabolism Sequence Alignment1 aGabaldón, T.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1509501301755nas a2200145   4500008004100000245003900041210003900080300001100119490000900130520117400139653015301313100001801466700001901484856010601503       2004                        eng d00aShaping the mitochondrial proteome0 aShaping the mitochondrial proteome  a212-200 v16593 aMitochondria are eukaryotic organelles that originated from a single bacterial endosymbiosis some 2 billion years ago. The transition from the ancestral endosymbiont to the modern mitochondrion has been accompanied by major changes in its protein content, the so-called proteome. These changes included complete loss of some bacterial pathways, amelioration of others and gain of completely new complexes of eukaryotic origin such as the ATP/ADP translocase and most of the mitochondrial protein import machinery. This renewal of proteins has been so extensive that only 14-16% of modern mitochondrial proteome has an origin that can be traced back to the bacterial endosymbiont. The rest consists of proteins of diverse origin that were eventually recruited to function in the organelle. This shaping of the proteome content reflects the transformation of mitochondria into a highly specialized organelle that, besides ATP production, comprises a variety of functions within the eukaryotic metabolism. Here we review recent advances in the fields of comparative genomics and proteomics that are throwing light on the origin and evolution of the mitochondrial proteome.10aAnimals Biological Transport Energy Metabolism Eukaryotic Cells/physiology *Evolution Humans Mitochondria/*physiology Phylogeny Proteome/*physiology1 aGabaldón, T.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1557605400772nas a2200145   4500008004100000245005700041210005600098300000800154490000800162653016300170653015000333100001800483700001900501856010600520       2003                        eng d00aReconstruction of the proto-mitochondrial metabolism0 aReconstruction of the protomitochondrial metabolism  a6090 v30110aAerobiosis Algorithms Alphaproteobacteria/chemistry/genetics/*metabolism Amino Acids/metabolism Animals Bacterial Proteins/chemistry/*metabolism Genome Genome10aBacterial Glycerol/metabolism Humans Lipid Metabolism Mitochondria/chemistry/genetics/*metabolism Phylogeny *Proteome Symbiosis Yeasts/metabolism1 aGabaldón, T.1 aHuynen, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12893934