NORMAL GENOMIC

• Storbeck S, Rolfes S, Raux-Deery E, Warren MJ, Jahn D, Layer G
• A novel pathway for the biosynthesis of heme in Archaea: genome-basedbioinformatic predictions and experimental evidence.
• Archaea. 2010; 2010: 175050-175050
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• Heme is an essential prosthetic group for many proteins involved infundamental biological processes in all three domains of life. InEukaryota and Bacteria heme is formed via a conserved and well-studiedbiosynthetic pathway. Surprisingly, in Archaea heme biosynthesis proceedsvia an alternative route which is poorly understood. In order to formulatea working hypothesis for this novel pathway, we searched 59 completelysequenced archaeal genomes for the presence of gene clusters consisting ofestablished heme biosynthetic genes and colocalized conserved candidategenes. Within the majority of archaeal genomes it was possible to identifysuch heme biosynthesis gene clusters. From this analysis we have been ableto identify several novel heme biosynthesis genes that are restricted toarchaea. Intriguingly, several of the encoded proteins display similarityto enzymes involved in heme d(1) biosynthesis. To initiate an experimentalverification of our proposals two Methanosarcina barkeri proteinspredicted to catalyze the initial steps of archaeal heme biosynthesis wererecombinantly produced, purified, and their predicted enzymatic functionsverified.

• Mulkidjanian AY, Galperin MY
• On the origin of life in the zinc world. 2. Validation of the hypothesison the photosynthesizing zinc sulfide edifices as cradles of life onEarth.
• Biol Direct. 2009; 4: 27-27
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• BACKGROUND: The accompanying article (A.Y. Mulkidjanian, Biology Direct4:26) puts forward a detailed hypothesis on the role of zinc sulfide (ZnS)in the origin of life on Earth. The hypothesis suggests that life emergedwithin compartmentalized, photosynthesizing ZnS formations of hydrothermalorigin (the Zn world), assembled in sub-aerial settings on the surface ofthe primeval Earth. RESULTS: If life started within photosynthesizing ZnScompartments, it should have been able to evolve under the conditions ofelevated levels of Zn2+ ions, byproducts of the ZnS-mediatedphotosynthesis. Therefore, the Zn world hypothesis leads to a set oftestable predictions regarding the specific roles of Zn2+ ions in modernorganisms, particularly in RNA and protein structures related to theprocession of RNA and the "evolutionarily old" cellular functions. Wechecked these predictions using publicly available data and obtainedevidence suggesting that the development of the primeval life forms up tothe stage of the Last Universal Common Ancestor proceeded in zinc-richsettings. Testing of the hypothesis has revealed the possible supportiverole of manganese sulfide in the primeval photosynthesis. In addition, wedemonstrate the explanatory power of the Zn world concept by elucidatingseveral points that so far remained without acceptable rationalization. Inparticular, this concept implies a new scenario for the separation ofBacteria and Archaea and the origin of Eukarya. CONCLUSION: The ability ofthe Zn world hypothesis to generate non-trivial veritable predictions andexplain previously obscure items gives credence to its key postulate thatthe development of the first life forms started within zinc-richformations of hydrothermal origin and was driven by solar UV irradiation.This concept implies that the geochemical conditions conducive to theorigin of life may have persisted only as long as the atmospheric CO2pressure remained above ca. 10 bar. This work envisions the first Earthbiotopes as photosynthesizing and habitable areas of porous ZnS and MnSprecipitates around primeval hot springs. Further work will be needed toprovide details on the life within these communities and to elucidate theprimordial (bio)chemical reactions. REVIEWERS: This article was reviewedby Arcady Mushegian, Eugene Koonin, and Patrick Forterre. For the fullreviews, please go to the Reviewers' reports section.

• Anderson IJ et al.
• Complete genome sequence of Methanocorpusculum labreanum type strain Z.
• Stand Genomic Sci. 2009; 1: 197-203
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• Methanocorpusculum labreanum is a methanogen belonging to the orderMethanomicrobiales within the archaeal kingdom Euryarchaeota. The typestrain Z was isolated from surface sediments of Tar Pit Lake in the LaBrea Tar Pits in Los Angeles, California. M. labreanum is of phylogeneticinterest because at the time the sequencing project began only one genomehad previously been sequenced from the order Methanomicrobiales. We reporthere the complete genome sequence of M. labreanum type strain Z and itsannotation. This is part of a 2006 Joint Genome Institute CommunitySequencing Program project to sequence genomes of diverse Archaea.

• Hinderhofer M, Walker CA, Friemel A, Stuermer CA, Moller HM, Reuter A
• Evolution of prokaryotic SPFH proteins.
• BMC Evol Biol. 2009; 9: 10-10
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• BACKGROUND: The SPFH protein superfamily is a diverse family of proteinswhose eukaryotic members are involved in the scaffolding ofdetergent-resistant microdomains. Recently the origin of the SPFH proteinshas been questioned. Instead, convergent evolution has been proposed.However, an independent, convergent evolution of three large prokaryoticand three eukaryotic families is highly unlikely, especially when othermechanisms such as lateral gene transfer which could also explain theirdistribution pattern have not yet been considered.To gain better insightinto this very diverse protein family, we have analyzed the genomes of 497microorganisms and investigated the pattern of occurrence as well as thegenomic vicinity of the prokaryotic SPFH members. RESULTS: According tosequence and operon structure, a clear division into 12 subfamilies wasevident. Three subfamilies (SPFH1, SPFH2 and SPFH5) show a conservedoperon structure and two additional subfamilies are linked to those threethrough functional aspects (SPFH1, SPFH3, SPFH4: interaction with FtsHprotease). Therefore these subgroups most likely share common ancestry.The complex pattern of occurrence among the different phyla is indicativeof lateral gene transfer. Organisms that do not possess a single SPFHprotein are almost exclusively endosymbionts or endoparasites. CONCLUSION:The conserved operon structure and functional similarities suggest that atleast 5 subfamilies that encompass almost 75% of all prokaryotic SPFHmembers share a common origin. Their similarity to the differenteukaryotic SPFH families, as well as functional similarities, suggeststhat the eukaryotic SPFH families originated from different prokaryoticSPFH families rather than one. This explains the difficulties in obtaininga consistent phylogenetic tree of the eukaryotic SPFH members.Phylogenetic evidence points towards lateral gene transfer as one sourceof the very diverse patterns of occurrence in bacterial species.

• Berthon J, Cortez D, Forterre P
• Genomic context analysis in Archaea suggests previously unrecognized linksbetween DNA replication and translation.
• Genome Biol. 2008; 9: 71-71
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• BACKGROUND: Comparative analysis of genomes is valuable to exploreevolution of genomes, deduce gene functions, or predict functional linkingbetween proteins. Here, we have systematically analyzed the genomicenvironment of all known DNA replication genes in 27 archaeal genomes toinfer new connections for DNA replication proteins from conserved genomicassociations. RESULTS: Two distinct sets of DNA replication genesfrequently co-localize in archaeal genomes: the first includes the genesfor PCNA, the small subunit of the DNA primase (PriS), and Gins15; thesecond comprises the genes for MCM and Gins23. Other genomic associationsof genes encoding proteins involved in informational processes that may befunctionally relevant at the cellular level have also been noted; inparticular, the association between the genes for PCNA, transcriptionfactor S, and NudF. Surprisingly, a conserved cluster of genes coding forproteins involved in translation or ribosome biogenesis (S27E, L44E, aIF-2alpha, Nop10) is almost systematically contiguous to the group of genescoding for PCNA, PriS, and Gins15. The functional relevance of thiscluster encoding proteins conserved in Archaea and Eukarya is stronglysupported by statistical analysis. Interestingly, the gene encoding theS27E protein, also known as metallopanstimulin 1 (MPS-1) in human, isoverexpressed in multiple cancer cell lines. CONCLUSION: Our genomecontext analysis suggests specific functional interactions for proteinsinvolved in DNA replication between each other or with proteins involvedin DNA repair or transcription. Furthermore, it suggests a previouslyunrecognized regulatory network coupling DNA replication and translationin Archaea that may also exist in Eukarya.

• Rogers MB, Watkins RF, Harper JT, Durnford DG, Gray MW, Keeling PJ
• A complex and punctate distribution of three eukaryotic genes derived bylateral gene transfer.
• BMC Evol Biol. 2007; 7: 89-89
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• BACKGROUND: Lateral gene transfer is increasingly invoked to explainphylogenetic results that conflict with our understanding of organismalrelationships. In eukaryotes, the most common observation interpreted inthis way is the appearance of a bacterial gene (one that is not clearlyderived from the mitochondrion or plastid) in a eukaryotic nuclear genome.Ideally such an observation would involve a single eukaryote or a smallgroup of related eukaryotes encoding a gene from a specific bacteriallineage. RESULTS: Here we show that several apparently simple cases oflateral transfer are actually more complex than they originally appeared:in these instances we find that two or more distantly related eukaryoticgroups share the same bacterial gene, resulting in a punctatedistribution. Specifically, we describe phylogenies of three core carbonmetabolic enzymes: transketolase, glyceraldehyde-3-phosphate dehydrogenaseand ribulose-5-phosphate-3-epimerase. Phylogenetic trees of each of theseenzymes includes a strongly-supported clade consisting of severaleukaryotes that are distantly related at the organismal level, but whoseenzymes are apparently all derived from the same lateral transfer. Withless sampling any one of these examples would appear to be a simple caseof bacterium-to-eukaryote lateral transfer; taken together, theirevolutionary histories cannot be so simple. The distributions of thesegenes may represent ancient paralogy events or genes that have beentransferred from bacteria to an ancient ancestor of the eukaryotes thatretain them. They may alternatively have been transferred laterally from abacterium to a single eukaryotic lineage and subsequently transferredbetween distantly related eukaryotes. CONCLUSION: Determining how complexthe distribution of a transferred gene is depends on the samplingavailable. These results show that seemingly simple cases may be revealedto be more complex with greater sampling, suggesting many bacterial genesfound in eukaryotic genomes may have a punctate distribution.

• Iyer LM, Balaji S, Koonin EV, Aravind L
• Evolutionary genomics of nucleo-cytoplasmic large DNA viruses.
• Virus Res. 2006; 117: 156-84
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• A previous comparative-genomic study of large nuclear and cytoplasmic DNAviruses (NCLDVs) of eukaryotes revealed the monophyletic origin of fourviral families: poxviruses, asfarviruses, iridoviruses, andphycodnaviruses [Iyer, L.M., Aravind, L., Koonin, E.V., 2001. Commonorigin of four diverse families of large eukaryotic DNA viruses. J. Virol.75 (23), 11720-11734]. Here we update this analysis by including therecently sequenced giant genome of the mimiviruses and several additionalgenomes of iridoviruses, phycodnaviruses, and poxviruses. The parsimoniousreconstruction of the gene complement of the ancestral NCLDV shows that itwas a complex virus with at least 41 genes that encoded the replicationmachinery, up to four RNA polymerase subunits, at least threetranscription factors, capping and polyadenylation enzymes, the DNApackaging apparatus, and structural components of an icosahedral capsidand the viral membrane. The phylogeny of the NCLDVs is reconstructed bycladistic analysis of the viral gene complements, and it is shown that thetwo principal lineages of NCLDVs are comprised of poxviruses grouped withasfarviruses and iridoviruses grouped with phycodnaviruses-mimiviruses.The phycodna-mimivirus grouping was strongly supported by several derivedshared characters, which seemed to rule out the previously suggested basalposition of the mimivirus [Raoult, D., Audic, S., Robert, C., Abergel, C.,Renesto, P., Ogata, H., La Scola, B., Suzan, M., Claverie, J.M. 2004. The1.2-megabase genome sequence of Mimivirus. Science 306 (5700), 1344-1350].These results indicate that the divergence of the major NCLDV familiesoccurred at an early stage of evolution, prior to the divergence of themajor eukaryotic lineages. It is shown that subsequent evolution of theNCLDV genomes involved lineage-specific expansion of paralogous genefamilies and acquisition of numerous genes via horizontal gene transferfrom the eukaryotic hosts, other viruses, and bacteria (primarily,endosymbionts and parasites). Amongst the expansions, there are multiplefamilies of predicted virus-specific signaling and regulatory domains.Most NCLDVs have also acquired large arrays of genes related to ubiquitinsignaling, and the animal viruses in particular have independently evolvedseveral defenses against apoptosis and immune response, including growthfactors and potential inhibitors of cytokine signaling. The mimivirusdisplays an enormous array of genes of bacterial provenance, including arepresentative of a new class of predicted papain-like peptidases. It isfurther demonstrated that a significant number of genes found in NCLDVsalso have homologs in bacteriophages, although a vertical relationshipbetween the NCLDVs and a particular bacteriophage group could not beestablished. On the basis of these observations, two alternative scenariosfor the origin of the NCLDVs and other groups of large DNA viruses ofeukaryotes are considered. One of these scenarios posits an early assemblyof an already large DNA virus precursor from which various large DNAviruses diverged through an ongoing process of displacement of theoriginal genes by xenologous or non-orthologous genes from varioussources. The second scenario posits convergent emergence, on multipleoccasions, of large DNA viruses from small plasmid-like precursors throughindependent accretion of similar sets of genes due to strong selectivepressures imposed by their life cycles and hosts.

• Adindla S, Inampudi KK, Guruprasad K, Guruprasad L
• Identification and analysis of novel tandem repeats in the cell surfaceproteins of archaeal and bacterial genomes using computational tools.
• Comp Funct Genomics. 2004; 5: 2-16
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• We have identified four novel repeats and two domains in cell surfaceproteins encoded by the Methanosarcina acetivorans genome and in somearchaeal and bacterial genomes. The repeats correspond to a certain numberof amino acid residues present in tandem in a protein sequence and eachrepeat is characterized by conserved sequence motifs. These correspond to:(a) a 42 amino acid (aa) residue RIVW repeat; (b) a 45 aa residue LGxLrepeat; (c) a 42 aa residue LVIVD repeat; and (d) a 54 aa residue LGFPrepeat. The domains correspond to a certain number of aa residues in aprotein sequence that do not comprise internal repeats. These correspondto: (a) a 200 aa residue DNRLRE domain; and (b) a 70 aa residue PEGAdomain. We discuss the occurrence of these repeats and domains in thedifferent proteins and genomes analysed in this work.

• Bauer M, Lombardot T, Teeling H, Ward NL, Amann RI, Glockner FO
• Archaea-like genes for C1-transfer enzymes in Planctomycetes: phylogeneticimplications of their unexpected presence in this phylum.
• J Mol Evol. 2004; 59: 571-86
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• The unexpected presence of archaea-like genes for tetrahydromethanopterin(H4MPT)-dependent enzymes in the completely sequence geiome of the aerobicmarine planctomycete Pirellula sp. strain 1 ("Rhodopirellula baltica") andin the currently sequenced genome of the aerobic freshwater planctomyceteGemmata obscuriglobus strain UQM2246 revives the discussion on the originof these genes in the bacterial domain. We compared the genomicarrangement of these genes in Planctomyetes and methylotrophicproteobacteria and perormed a phylogenetic analysis of the encoded proteinsequences to address the question whether the genes have been present inthe common ancestor of Bacteria and Archaea or were transferred laterallyfrom the archaeal to the bacterial domain and herein. Although thisquestion could not be solved using the data presented here, someconstraints on the evolution of the genes involved in archaeal and)acterial H4MPT-dependent C1-transfer may be proposed: (i) lateral genetransfer (LGT) from Archea to a common ancestor of Proteobacteria andPlanctomycetes seems more likely than the presence of the genes in thecommon ancestor of Bacteria and Archaea; (ii) a single event ofinterdomain LGT can e favored over two independent events; and (iii) theirchacal donor of the genes might have been a repesentative of theMethanosarcinales. In the bacterial domain, the acquired genes evolvedaccording to distinct environmental and metabolic constraints, reflectedby specific rearrangements of gene order, gene recruitment, and geneduplication, with subsequent functional specialization. During the courseof evolution, genes were lost from some planctomycete genomes or replacedby orthologous genes from proteobacterial lineages.

• Kebaara B, Nazarenus T, Taylor R, Forch A, Atkin AL
• The Upf-dependent decay of wild-type PPR1 mRNA depends on its 5'-UTR andfirst 92 ORF nucleotides.
• Nucleic Acids Res. 2003; 31: 3157-65
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• mRNAs containing premature translation termination codons (nonsense mRNAs)are targeted for deadenylation-independent degradation in a mechanism thatdepends on Upf1p, Upf2p and Upf3p. This decay pathway is often callednonsense- mediated mRNA decay (NMD). Nonsense mRNAs are decapped by Dcp1pand then degraded 5' to 3' by Xrn1p. In the yeast Saccharomycescerevisiae, a significant number of wild-type mRNAs accumulate in upfmutants. Wild-type PPR1 mRNA is one of these mRNAs. Here we show that PPR1mRNA degradation depends on the Upf proteins, Dcp1p, Xrn1p and Hrp1p. Wehave mapped an Upf1p-dependent destabilizing element to a region locatedwithin the 5'-UTR and the first 92 bases of the PPR1 ORF. This elementtargets PPR1 mRNA for Upf-dependent decay by a novel mechanism.

• Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, Pellegrini L
• The rhomboids: a nearly ubiquitous family of intramembrane serineproteases that probably evolved by multiple ancient horizontal genetransfers.
• Genome Biol. 2003; 4: 19-19
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• BACKGROUND: The rhomboid family of polytopic membrane proteins shows alevel of evolutionary conservation unique among membrane proteins. Theyare present in nearly all the sequenced genomes of archaea, bacteria andeukaryotes, with the exception of several species with small genomes. Onthe basis of experimental studies with the developmental regulatorrhomboid from Drosophila and the AarA protein from the bacteriumProvidencia stuartii, the rhomboids are thought to be intramembrane serineproteases whose signaling function is conserved in eukaryotes andprokaryotes. RESULTS: Phylogenetic tree analysis carried out using severalindependent methods for tree constructions and the correspondingstatistical tests suggests that, despite its broad distribution in allthree superkingdoms, the rhomboid family was not present in the lastuniversal common ancestor of extant life forms. Instead, we propose thatrhomboids evolved in bacteria and have been acquired by archaea andeukaryotes through several independent horizontal gene transfers. Ineukaryotes, two distinct, ancient acquisitions apparently gave rise to thetwo major subfamilies, typified by rhomboid and PARL(presenilins-associated rhomboid-like protein), respectively. Subsequentevolution of the rhomboid family in eukaryotes proceeded by multipleduplications and functional diversification through the addition of extratransmembrane helices and other domains in different orientations relativeto the conserved core that harbors the protease activity. CONCLUSIONS:Although the near-universal presence of the rhomboid family in bacteria,archaea and eukaryotes appears to suggest that this protein is part of theheritage of the last universal common ancestor, phylogenetic tree analysisindicates a likely bacterial origin with subsequent dissemination byhorizontal gene transfer. This emphasizes the importance of explicitphylogenetic analysis for the reconstruction of ancestral life forms. Ahypothetical scenario for the origin of intracellular membrane proteasesfrom membrane transporters is proposed.

• Omelchenko MV, Makarova KS, Wolf YI, Rogozin IB, Koonin EV
• Evolution of mosaic operons by horizontal gene transfer and genedisplacement in situ.
• Genome Biol. 2003; 4: 55-55
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• BACKGROUND: Shuffling and disruption of operons and horizontal genetransfer are major contributions to the new, dynamic view of prokaryoticevolution. Under the 'selfish operon' hypothesis, operons are viewed asmobile genetic entities that are constantly disseminated via horizontalgene transfer, although their retention could be favored by the advantageof coregulation of functionally linked genes. Here we apply comparativegenomics and phylogenetic analysis to examine horizontal transfer ofentire operons versus displacement of individual genes within operons byhorizontally acquired orthologs and independent assembly of the same orsimilar operons from genes with different phylogenetic affinities.RESULTS: Since a substantial number of operons have been identifiedexperimentally in only a few model bacteria, evolutionarily conserved genestrings were analyzed as surrogates of operons. The phylogeneticaffinities within these predicted operons were assessed first by sequencesimilarity analysis and then by phylogenetic analysis, includingstatistical tests of tree topology. Numerous cases of apparent horizontaltransfer of entire operons were detected. However, it was shown thatapparent horizontal transfer of individual genes or arrays of genes withinoperons is not uncommon either and results in xenologous gene displacementin situ, that is, displacement of an ancestral gene by a horizontallytransferred ortholog from a taxonomically distant organism without changeof the local gene organization. On rarer occasions, operons might haveevolved via independent assembly, in part from horizontally acquiredgenes. CONCLUSIONS: The discovery of in situ gene displacement shows thatcombination of rampant horizontal gene transfer with selection forpreservation of operon structure provides for events in prokaryoticevolution that, a priori, seem improbable. These findings also emphasizethat not all aspects of operon evolution are selfish, with operonintegrity maintained by purifying selection at the organism level.

• Nesbo CL, Boucher Y, Doolittle WF
• Defining the core of nontransferable prokaryotic genes: the euryarchaealcore.
• J Mol Evol. 2001; 53: 340-50
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• If lateral gene transfer (LGT) has affected all genes over the course ofprokaryotic evolution, reconstruction of organismal phylogeny iscompromised. However, if a core of genes is immune to transfer, then theevolutionary history of that core might be our most reliable guide to theevolution of organisms. Such a core should be preferentially included inthe subset of genes shared by all organisms, but where universallyconserved genes have been analyzed, there is too little phylogeneticsignal to allow determination of whether or not they indeed have the samehistory (Hansmann and Martin 2000; Teichmann and Mitchison 1999). Here welook at a more restricted set, 521 homologous genes (COGs) simultaneouslypresent in four sequenced euryarchaeal genomes. Although there is overalllittle robust phylogenetic signal in this data set, there is, amongwell-supported trees, strong representation of all three possiblefour-taxon topologies. "Informational" genes seem no less subject to LGTthan are "operational genes," within the euryarchaeotes. We conclude that(i) even in this collection of conserved genes there has been extensiveLGT (orthologous gene replacement) and (ii) the notion that there is acore of nontransferable genes (the "core hypothesis") has not been provenand may be unprovable.

• Daugeron MC, Mauxion F, Seraphin B
• The yeast POP2 gene encodes a nuclease involved in mRNA deadenylation.
• Nucleic Acids Res. 2001; 29: 2448-55
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• The major mRNA degradation pathway involves deadenylation of the targetmolecule followed by decapping and, finally, 5'-->3' exonuclease digestionof the mRNA body. While yeast factors involved in the decapping andexonuclease degradation steps have been identified, the nature of thefactor(s) involved in the deadenylation step remained elusive. Databasesearches for yeast proteins related to the mammalian deadenylase PARNidentified the Pop2 protein (Pop2p) as a potential deadenylase. WhilePop2p was previously identified as a factor affecting transcription, weidentified a non-canonical RNase D sequence signature in its sequence.Analysis of the fate of a reporter mRNA in a pop2 mutant demonstrates thatPop2p is required for efficient mRNA degradation in vivo. Characterisationof mRNA degradation intermediates accumulating in this mutant supports theinvolvement of Pop2p in mRNA deadenylation in vivo. Similar phenotypes areobserved in yeast strains lacking the Ccr4 protein, which is known to beassociated with Pop2p. A recombinant Pop2p fragment encompassing theputative catalytic domain degrades poly(A) in vitro demonstrating thatPop2p is a nuclease. We also demonstrate that poly(A) is a bettercompetitor than poly(G) or poly(C) of the Pop2p nuclease activity.Altogether, our study indicates that Pop2p is a nuclease subunit of theyeast deadenylase and suggests that Pop2p homologues in other species mayhave similar functions.

• Jin SW et al.
• In Caenorhabditis elegans, the RNA-binding domains of the cytoplasmicpolyadenylation element binding protein FOG-1 are needed to regulate germcell fates.
• Genetics. 2001; 159: 1617-30
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• FOG-1 controls germ cell fates in the nematode Caenorhabditis elegans.Sequence analyses revealed that FOG-1 is a cytoplasmic polyadenylationelement binding (CPEB) protein; similar proteins from other species havebeen shown to bind messenger RNAs and regulate their translation. Ouranalyses of fog-1 mutations indicate that each of the three RNA-bindingdomains of FOG-1 is essential for activity. In addition, biochemical testsshow that FOG-1 is capable of binding RNA sequences in the 3'-untranslatedregion of its own message. Finally, genetic assays reveal that fog-1functions zygotically, that the small fog-1 transcript has no detectablefunction, and that missense mutations in fog-1 cause a dominant negativephenotype. This last observation suggests that FOG-1 acts in a complex, oras a multimer, to regulate translation. On the basis of these data, wepropose that FOG-1 binds RNA to regulate germ cell fates and that it doesso by controlling the translation of its targets. One of these targetsmight be the fog-1 transcript itself.

• Tumbula DL, Whitman WB
• Genetics of Methanococcus: possibilities for functional genomics inArchaea.
• Mol Microbiol. 1999; 33: 1-7
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• Although the genomic sequences of a number of Archaea have been completedin the last three years, genetic systems in the sequenced organisms areabsent. In contrast, genetic studies of the mesophiles in the archaealgenus Methanococcus have become commonplace following the recentdevelopments of antibiotic resistance markers, DNA transformation methods,reporter genes, shuttle vectors and expression vectors. These developmentshave led to investigations of the transcription of the genes for hydrogenmetabolism, nitrogen fixation and flagellin assembly. These geneticsystems can potentially be used to analyse the genomic sequence of thehyperthermophile Methanococcus jannaschii, addressing questions of itsphysiology and the function of its many uncharacterized open readingframes. Thus, the sequence of M. jannaschii can serve as a starting pointfor gene isolation, while in vivo genetics in the mesophilic methanococcican provide the experimental systems to test the predictions fromgenomics.

• Gerstein M
• A structural census of genomes: comparing bacterial, eukaryotic, andarchaeal genomes in terms of protein structure.
• J Mol Biol. 1997; 274: 562-76
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• Representative genomes from each of the three kingdoms of life arecompared in terms of protein structure, in particular, those ofHaemophilus influenzae (a bacteria), Methanococcus jannaschii (anarchaeon), and yeast (a eukaryote). The comparison is in the form of acensus (or comprehensive accounting) of the relative occurrence ofsecondary and tertiary structures in the genomes, which particularemphasis on patterns of supersecondary structure. Comparison of secondarystructure shows that the three genomes have nearly the same overallsecondary-structure content, although they differ markedly in amino acidcomposition. Comparison of super-secondary structure, using a novel"frequent-words" approach, shows that yeast has a preponderance ofconsecutive strands (e.g. beta-beta-beta patterns), Haemophilus,consecutive helices (alpha-alpha-alpha), and Methanococcus, alternatinghelix-strand structures (beta-alpha-beta). Yeast also has significantlymore helical membrane proteins than the other two genomes, with most ofthe differences concentrated in proteins containing two transmembranesegments. Comparison of tertiary structure (by sequence matching anddomain-level clustering) highlights the substantial duplication in eachgenome (approximately 30% to 50%), with the degree of duplicationfollowing similar patterns in all three. Many sequence families are sharedamong the genomes, with the degree of overlap between any two genomesbeing roughly similar. In total, the three genomes contain 148 of theapproximately 300 known protein folds. Forty-five of these 148 that arepresent in all three genomes are especially enriched in mixedsuper-secondary structures (alpha/beta). Moreover, the five most common ofthese 45 (the "top-5") have a remarkably similar super-secondary structurearchitecture, containing a central sheet of parallel strands with helicespacked onto at least one face and beta-alpha-beta connections betweenadjacent strands. These most basic molecular parts, which, presumably,were present in the last common ancestor to the three Kingdoms, includethe TIM-barrel, Rossmann, flavodoxin, thiamin-binding, andP-loop-hydrolase folds.

• Koonin EV, Mushegian AR, Galperin MY, Walker DR
• Comparison of archaeal and bacterial genomes: computer analysis of proteinsequences predicts novel functions and suggests a chimeric origin for thearchaea.
• Mol Microbiol. 1997; 25: 619-37
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• Protein sequences encoded in three complete bacterial genomes, those ofHaemophilus influenzae, Mycoplasma genitalium and Synechocystis sp., andthe first available archaeal genome sequence, that of Methanococcusjannaschii, were analysed using the BLAST2 algorithm and methods for aminoacid motif detection. Between 75% and 90% of the predicted proteinsencoded in each of the bacterial genomes and 73% of the M. jannaschiiproteins showed significant sequence similarity to proteins from otherspecies. The fraction of bacterial and archaeal proteins containingregions conserved over long phylogenetic distances is nearly the same andclose to 70%. Functions of 70-85% of the bacterial proteins and about 70%of the archaeal proteins were predicted with varying precision. Thiscontrasts with the previous report that more than half of the archaealproteins have no homologues and shows that, with more sensitive methodsand detailed analysis of conserved motifs, archaeal genomes become asamenable to meaningful interpretation by computer as bacterial genomes.The analysis of conserved motifs resulted in the prediction of a number ofpreviously undetected functions of bacterial and archaeal proteins and inthe identification of novel protein families. In spite of the generallyhigh conservation of protein sequences, orthologues of 25% or less of theM. jannaschii genes were detected in each individual completely sequencedgenome, supporting the uniqueness of archaea as a distinct domain of life.About 53% of the M. jannaschii proteins belong to families of paralogues,a fraction similar to that in bacteria with larger genomes, such asSynechocystis sp. and Escherichia coli, but higher than that in H.influenzae, which has approximately the same number of genes as M.jannaschii. Certain groups of proteins, e.g. molecular chaperones and DNArepair enzymes, thought to be ubiquitous and represented in the minimalgene set derived by bacterial genome comparison, are missing in M.jannaschii, indicating massive non-orthologous displacement of genesresponsible for essential functions. An unexpectedly large fraction of theM. jannaschii gene products, 44%, shows significantly higher similarity tobacterial than to eukaryotic proteins, compared with 13% that haveeukaryotic proteins as their closest homologues (the rest of the proteinsshow approximately the same level of similarity to bacterial andeukaryotic homologues or have no homologues). Proteins involved intranslation, transcription, replication and protein secretion are mostclosely related to eukaryotic proteins, whereas metabolic enzymes,metabolite uptake systems, enzymes for cell wall biosynthesis and manyuncharacterized proteins appear to be 'bacterial'. A similar prevalence ofproteins of apparent bacterial origin was observed among the currentlyavailable sequences from the distantly related archaeal genus, Sulfolobus.It is likely that the evolution of archaea included at least one majormerger between ancestral cells from the bacterial lineage and the lineageleading to the eukaryotic nucleocytoplasm.

• MacIntyre RJ
• Molecular evolution: codes, clocks, genes and genomes.
• Bioessays. 1994; 16: 699-703
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• The discoveries, advancements and continuing controversies in the field ofmolecular evolution are reviewed. Topics summarized are (1) the evolutionof the genetic code, (2) gene evolution including the demonstration ofhomology, estimation of sequence divergence, phylogenetic trees, themolecular clock and the origin of genes and gene families by variousgenetic mechanisms, and (3) eukaryotic genome evolution, including thehighly repeated satellite sequences, the interspersed and potentiallymobile repeated sequences and the unique sequence fraction of the genome.

• Weil CF, Sherf BA, Reeve JN
• A comparison of the methyl reductase genes and gene products.
• Can J Microbiol. 1989; 35: 101-8
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• The DNA sequences encoding component C of methyl coenzyme M reductase (mcrgenes) in Methanothermus fervidus, Methanobacterium thermoautotrophicum,Methanococcus vannielii, and Methanosarcina barkeri have been published.Comparisons of transcription initiation and termination sites and of theamino acid sequences of the mcr gene products are presented. Structuralfeatures conserved within the amino acid sequences are identified and acomparison of methyl reductase with other disulfide bond synthesizingenzymes is presented.