00426nas a2200109   4500008004100000245006200041210006100103260004700164490000800211100001800219856007900237       2008                        eng d00aComparative genomics-based prediction of protein function0 aComparative genomicsbased prediction of protein function  bM. Starkey and R. Elaswarapu, Humana press0 v4391 aGabaldón, T.  uhttp://www.springerprotocols.com/Abstract/doi/10.1007/978-1-59745-188-8_2600550nas a2200157   4500008004100000245007400041210006900115260002300184300001200207100001800219700001200237700001600249700001600265700001300281856009800294       2008                        eng d00aThe core of a minimal gene set: insights from natural reduced genomes0 acore of a minimal gene set insights from natural reduced genomes  aUSAbThe MIT Press  a347-3661 aGabaldón, T.1 aGil, R.1 aPeretó, J.1 aLatorre, A.1 aMoya, A.  uhttps://www.clinbioinfosspa.es/content/core-minimal-gene-set-insights-natural-reduced-genomes02003nas a2200181   4500008004100000245007400041210006900115300001100184490000700195520123100202653013101433653008301564100002101647700001401668700001501682700001801697856010601715       2008                        eng d00aPhylomeDB: a database for genome-wide collections of gene phylogenies0 aPhylomeDB a database for genomewide collections of gene phylogen  aD491-60 v363 aThe complete collection of evolutionary histories of all genes in a genome, also known as phylome, constitutes a valuable source of information. The reconstruction of phylomes has been previously prevented by large demands of time and computer power, but is now feasible thanks to recent developments in computers and algorithms. To provide a publicly available repository of complete phylomes that allows researchers to access and store large-scale phylogenomic analyses, we have developed PhylomeDB. PhylomeDB is a database of complete phylomes derived for different genomes within a specific taxonomic range. All phylomes in the database are built using a high-quality phylogenetic pipeline that includes evolutionary model testing and alignment trimming phases. For each genome, PhylomeDB provides the alignments, phylogentic trees and tree-based orthology predictions for every single encoded protein. The current version of PhylomeDB includes the phylomes of Human, the yeast Saccharomyces cerevisiae and the bacterium Escherichia coli, comprising a total of 32 289 seed sequences with their corresponding alignments and 172 324 phylogenetic trees. PhylomeDB can be publicly accessed at http://phylomedb.bioinfo.cipf.es.10aAncient Humans *Phylogeny Proteins/classification/genetics Saccharomyces cerevisiae/classification/genetics Sequence Alignment10aBase Sequence Escherichia coli/classification/genetics Genes *Genomics History1 aHuerta-Cepas, J.1 aBueno, A.1 aDopazo, J.1 aGabaldón, T.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1796229702090nas 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=1798326502363nas a2200193   4500008004100000245002200041210001800063300000900081490000600090520176400096653003301860653000801893653009301901100002101994700001502015700001502030700001802045856010602063       2007                        eng d00aThe human phylome0 ahuman phylome  aR1090 v83 aBACKGROUND: Phylogenomics analyses serve to establish evolutionary relationships among organisms and their genes. A phylome, the complete collection of all gene phylogenies in a genome, constitutes a valuable source of information, but its use in large genomes still constitutes a technical challenge. The use of phylomes also requires the development of new methods that help us to interpret them. RESULTS: We reconstruct here the human phylome, which includes the evolutionary relationships of all human proteins and their homologs among 39 fully sequenced eukaryotes. Phylogenetic techniques used include alignment trimming, branch length optimization, evolutionary model testing and maximum likelihood and Bayesian methods. Although differences with alternative topologies are minor, most of the trees support the Coelomata and Unikont hypotheses as well as the grouping of primates with laurasatheria to the exclusion of rodents. We assess the extent of gene duplication events and their relationship with the functional roles of the protein families involved. We find support for at least one, and probably two, rounds of whole genome duplications before vertebrate radiation. Using a novel algorithm that is independent from a species phylogeny, we derive orthology and paralogy relationships of human proteins among eukaryotic genomes. CONCLUSION: Topological variations among phylogenies for different genes are to be expected, highlighting the danger of gene-sampling effects in phylogenomic analyses. Several links can be established between the functions of gene families duplicated at certain phylogenetic splits and major evolutionary transitions in those lineages. The pipeline implemented here can be easily adapted for use in other organisms.10aAnimals *Evolution Evolution10aDNA10aMolecular Gene Duplication *Genome Humans *Phylogeny Proteins/genetics Sequence Analysis1 aHuerta-Cepas, J.1 aDopazo, H.1 aDopazo, J.1 aGabaldón, T.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1756792402580nas a2200253   4500008004100000245009100041210006900132300001200201490000700213520154400220653002301764653025501787100001702042700001702059700002502076700001802101700002102119700002002140700001302160700002002173700001302193700001402206856010602220       2007                        eng d00aPeroxisomeDB: a database for the peroxisomal proteome, functional genomics and disease0 aPeroxisomeDB a database for the peroxisomal proteome functional   aD815-220 v353 aPeroxisomes are essential organelles of eukaryotic origin, ubiquitously distributed in cells and organisms, playing key roles in lipid and antioxidant metabolism. Loss or malfunction of peroxisomes causes more than 20 fatal inherited conditions. We have created a peroxisomal database (http://www.peroxisomeDB.org) that includes the complete peroxisomal proteome of Homo sapiens and Saccharomyces cerevisiae, by gathering, updating and integrating the available genetic and functional information on peroxisomal genes. PeroxisomeDB is structured in interrelated sections ’Genes’, ’Functions’, ’Metabolic pathways’ and ’Diseases’, that include hyperlinks to selected features of NCBI, ENSEMBL and UCSC databases. We have designed graphical depictions of the main peroxisomal metabolic routes and have included updated flow charts for diagnosis. Precomputed BLAST, PSI-BLAST, multiple sequence alignment (MUSCLE) and phylogenetic trees are provided to assist in direct multispecies comparison to study evolutionary conserved functions and pathways. Highlights of the PeroxisomeDB include new tools developed for facilitating (i) identification of novel peroxisomal proteins, by means of identifying proteins carrying peroxisome targeting signal (PTS) motifs, (ii) detection of peroxisomes in silico, particularly useful for screening the deluge of newly sequenced genomes. PeroxisomeDB should contribute to the systematic characterization of the peroxisomal proteome and facilitate system biology approaches on the organelle.10aAnimals *Databases10aProtein Genomics Humans Internet Mice Peroxisomal Disorders/*genetics Peroxisomes/*metabolism Protein Sorting Signals Proteome/chemistry/*genetics/*physiology Rats Saccharomyces cerevisiae Proteins/genetics/physiology Software User-Computer Interface1 aSchluter, A.1 aFourcade, S.1 aDomenech-Estevez, E.1 aGabaldón, T.1 aHuerta-Cepas, J.1 aBerthommier, G.1 aRipp, R.1 aWanders, R., J.1 aPoch, O.1 aPujol, A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1713519002437nas a2200265   4500008004100000245009200041210006900133300001100202490000700213520143600220653005301656653002601709653002201735653005701757653004501814653008601859100001601945700002001961700001501981700002101996700001802017700001502035700001502050856010602065       2007                        eng d00aPhylemon: a suite of web tools for molecular evolution, phylogenetics and phylogenomics0 aPhylemon a suite of web tools for molecular evolution phylogenet  aW38-420 v353 aPhylemon is an online platform for phylogenetic and evolutionary analyses of molecular sequence data. It has been developed as a web server that integrates a suite of different tools selected among the most popular stand-alone programs in phylogenetic and evolutionary analysis. It has been conceived as a natural response to the increasing demand of data analysis of many experimental scientists wishing to add a molecular evolution and phylogenetics insight into their research. Tools included in Phylemon cover a wide yet selected range of programs: from the most basic for multiple sequence alignment to elaborate statistical methods of phylogenetic reconstruction including methods for evolutionary rates analyses and molecular adaptation. Phylemon has several features that differentiates it from other resources: (i) It offers an integrated environment that enables the direct concatenation of evolutionary analyses, the storage of results and handles required data format conversions, (ii) Once an outfile is produced, Phylemon suggests the next possible analyses, thus guiding the user and facilitating the integration of multi-step analyses, and (iii) users can define and save complete pipelines for specific phylogenetic analysis to be automatically used on many genes in subsequent sessions or multiple genes in a single session (phylogenomics). The Phylemon web server is available at http://phylemon.bioinfo.cipf.es.10aAnimals Computational Biology/*methods Databases10aDNA Sequence Analysis10aGenetic Evolution10aMolecular Genetic Techniques Humans *Internet Models10aProtein Software User-Computer Interface10aStatistical *Phylogeny Programming Languages Sequence Alignment Sequence Analysis1 aTarraga, J.1 aMedina, Ignacio1 aArbiza, L.1 aHuerta-Cepas, J.1 aGabaldón, T.1 aDopazo, J.1 aDopazo, H.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1745234600409nas 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=978019929918802088nas a2200217   4500008004100000245006100041210006100102300001200163490000800175520132100183653013101504653002201635653001601657100001801673700001601691700001601707700001201723700001601735700001301751856010601764       2007                        eng d00aStructural analyses of a hypothetical minimal metabolism0 aStructural analyses of a hypothetical minimal metabolism  a1751-620 v3623 aBy integrating data from comparative genomics and large-scale deletion studies, we previously proposed a minimal gene set comprising 206 protein-coding genes. To evaluate the consistency of the metabolism encoded by such a minimal genome, we have carried out a series of computational analyses. Firstly, the topology of the minimal metabolism was compared with that of the reconstructed networks from natural bacterial genomes. Secondly, the robustness of the metabolic network was evaluated by simulated mutagenesis and, finally, the stoichiometric consistency was assessed by automatically deriving the steady-state solutions from the reaction set. The results indicated that the proposed minimal metabolism presents stoichiometric consistency and that it is organized as a complex power-law network with topological parameters falling within the expected range for a natural metabolism of its size. The robustness analyses revealed that most random mutations do not alter the topology of the network significantly, but do cause significant damage by preventing the synthesis of several compounds or compromising the stoichiometric consistency of the metabolism. The implications that these results have on the origins of metabolic complexity and the theoretical design of an artificial minimal cell are discussed.10a*Cell Physiological Phenomena Cells/*metabolism Cluster Analysis *Computer Simulation *Metabolic Networks and Pathways *Models10aBiological Models10aStatistical1 aGabaldón, T.1 aPeretó, J.1 aMontero, F.1 aGil, R.1 aLatorre, A.1 aMoya, A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1751002201615nas a2200133   4500008004100000245008900041210006900130300001200199490000800211520100500219653013301224100001801357856010601375       2006                        eng d00aComputational approaches for the prediction of protein function in the mitochondrion0 aComputational approaches for the prediction of protein function   aC1121-80 v2913 aUnderstanding a complex biological system, such as the mitochondrion, requires the identification of the complete repertoire of proteins targeted to the organelle, the characterization of these, and finally, the elucidation of the functional and physical interactions that occur within the mitochondrion. In the last decade, significant developments have contributed to increase our understanding of the mitochondrion, and among these, computational research has played a significant role. Not only general bioinformatics tools have been applied in the context of the mitochondrion, but also some computational techniques have been specifically developed to address problems that arose from within the mitochondrial research field. In this review the contribution of bioinformatics to mitochondrial biology is addressed through a survey of current computational methods that can be applied to predict which proteins will be localized to the mitochondrion and to unravel their functional interactions.10a*Computational Biology *Computer Simulation Humans Mitochondria/*metabolism Mitochondrial Proteins/genetics/*metabolism Mutation1 aGabaldón, T.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1687083002737nas 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=1655631402676nas 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=1567081301232nas a2200121   4500008004100000245006600041210006500107300001000172490000600182520079800188100001800986856010601004       2005                        eng d00aEvolution of proteins and proteomes: a phylogenetics approach0 aEvolution of proteins and proteomes a phylogenetics approach  a51-610 v13 aThe study of evolutionary relationships among protein sequences was one of the first applications of bioinformatics. Since then, and accompanying the wealth of biological data produced by genome sequencing and other high-throughput techniques, the use of bioinformatics in general and phylogenetics in particular has been gaining ground in the study of protein and proteome evolution. Nowadays, the use of phylogenetics is instrumental not only to infer the evolutionary relationships among species and their genome sequences, but also to reconstruct ancestral states of proteins and proteomes and hence trace the paths followed by evolution. Here I survey recent progress in the elucidation of mechanisms of protein and proteome evolution in which phylogenetics has played a determinant role.1 aGabaldón, T.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1932585301787nas 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=1576356100480nas a2200145   4500008004100000245003100041210003100072300000900103490000600112653006100118100001400179700001700193700001800210856010600228       2004                        eng d00aPerceptions about postdocs0 aPerceptions about postdocs  a11040 v510aEurope *Fellowships and Scholarships *Research Personnel1 aVella, F.1 aMietchen, D.1 aGabaldón, T.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1557792002058nas 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