Biomedical subjects

Yuri I Wolf

Publications and source records attributed to Yuri I Wolf.

At least 19 recordsLinked to original sources

PubMed2006

Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus.

BACKGROUND: The interpandemic evolution of the influenza A virus hemagglutinin (HA) protein is commonly considered a paragon of rapid evolutionary change under positive selection in which amino acid replacements are fixed by virtue of their effect on antigenicity, enabling the virus to evade immune surveillance. RESULTS: We performed phylogenetic analyses of the recently obtained large and relatively unbiased samples of the HA sequences from 1995-2005 isolates of the H3N2 and H1N1 subtypes of influenza A virus. Unexpectedly, it was found that the evolution of H3N2 HA includes long intervals of generally neutral sequence evolution without apparent substantial antigenic change ("stasis" periods) that are characterized by an excess of synonymous over nonsynonymous substitutions per site, lack of association of amino acid replacements with epitope regions, and slow extinction of coexisting virus lineages. These long periods of stasis are punctuated by shorter intervals of rapid evolution under positive selection during which new dominant lineages quickly displace previously coexisting ones. The preponderance of positive selection during intervals of rapid evolution is supported by the dramatic excess of amino acid replacements in the epitope regions of HA compared to replacements in the rest of the HA molecule. In contrast, the stasis intervals showed a much more uniform distribution of replacements over the HA molecule, with a statistically significant difference in the rate of synonymous over nonsynonymous substitution in the epitope regions between the two modes of evolution. A number of parallel amino acid replacements - the same amino acid substitution occurring independently in different lineages - were also detected in H3N2 HA. These parallel mutations were, largely, associated with periods of rapid fitness change, indicating that there are major limitations on evolutionary pathways during antigenic change. The finding that stasis is the prevailing modality of H3N2 evolution suggests that antigenic changes that lead to an increase in fitness typically result from epistatic interactions between several amino acid substitutions in the HA and, perhaps, other viral proteins. The strains that become dominant due to increased fitness emerge from low frequency strains thanks to the last amino acid replacement that completes the set of replacements required to produce a significant antigenic change; no subset of substitutions results in a biologically significant antigenic change and corresponding fitness increase. In contrast to H3N2, no clear intervals of evolution under positive selection were detected for the H1N1 HA during the same time span. Thus, the ascendancy of H1N1 in some seasons is, most likely, caused by the drop in the relative fitness of the previously prevailing H3N2 lineages as the fraction of susceptible hosts decreases during the stasis intervals. CONCLUSION: We show that the common view of the evolution of influenza virus as a rapid, positive selection-driven process is, at best, incomplete. Rather, the interpandemic evolution of influenza appears to consist of extended intervals of stasis, which are characterized by neutral sequence evolution, punctuated by shorter intervals of rapid fitness increase when evolutionary change is driven by positive selection. These observations have implications for influenza surveillance and vaccine formulation; in particular, the possibility exists that parallel amino acid replacements could serve as a predictor of new dominant strains. REVIEWERS: Ron Fouchier (nominated by Andrey Rzhetsky), David Krakauer, Christopher Lee.

Journal Article↗

PubMed2006

Genome-wide analysis of substrate specificities of the Escherichia coli haloacid dehalogenase-like phosphatase family.

Haloacid dehalogenase (HAD)-like hydrolases are a vast superfamily of largely uncharacterized enzymes, with a few members shown to possess phosphatase, beta-phosphoglucomutase, phosphonatase, and dehalogenase activities. Using a representative set of 80 phosphorylated substrates, we characterized the substrate specificities of 23 soluble HADs encoded in the Escherichia coli genome. We identified small molecule phosphatase activity in 21 HADs and beta-phosphoglucomutase activity in one protein. The E. coli HAD phosphatases show high catalytic efficiency and affinity to a wide range of phosphorylated metabolites that are intermediates of various metabolic reactions. Rather than following the classical "one enzyme-one substrate" model, most of the E. coli HADs show remarkably broad and overlapping substrate spectra. At least 12 reactions catalyzed by HADs currently have no EC numbers assigned in Enzyme Nomenclature. Surprisingly, most HADs hydrolyzed small phosphodonors (acetyl phosphate, carbamoyl phosphate, and phosphoramidate), which also serve as substrates for autophosphorylation of the receiver domains of the two-component signal transduction systems. The physiological relevance of the phosphatase activity with the preferred substrate was validated in vivo for one of the HADs, YniC. Many of the secondary activities of HADs might have no immediate physiological function but could comprise a reservoir for evolution of novel phosphatases.

Catalysis↗

PubMed2006

Evolutionary systems biology: links between gene evolution and function.

The recent accumulation of genome-wide data on various facets of gene expression, function and evolution stimulated the emergence of a new field, evolutionary systems biology. Many significant correlations were detected between variables that characterize the functioning of a gene, such as expression level, knockout effect, connectivity of genetic and protein-protein interaction networks, and variables that describe gene evolution, such as sequence evolution rate and propensity for gene loss. The first attempts on multidimensional analysis of genomic data yielded composite variables that describe the 'status' of a gene in the genomic community. However, it remains uncertain whether different functional variables affect gene evolution synergistically or there is a single, dominant factor. The number of translation events, linked to selection for translational robustness, was proposed as a candidate for such a major determinant of protein evolution. These developments show that, although the methodological basis of evolutionary systems biology is not yet fully solidified, this area of research is already starting to yield fundamental biological insights.

Evolution, Molecular↗

PubMed2006

The cyanobacterial genome core and the origin of photosynthesis.

Comparative analysis of 15 complete cyanobacterial genome sequences, including "near minimal" genomes of five strains of Prochlorococcus spp., revealed 1,054 protein families [core cyanobacterial clusters of orthologous groups of proteins (core CyOGs)] encoded in at least 14 of them. The majority of the core CyOGs are involved in central cellular functions that are shared with other bacteria; 50 core CyOGs are specific for cyanobacteria, whereas 84 are exclusively shared by cyanobacteria and plants and/or other plastid-carrying eukaryotes, such as diatoms or apicomplexans. The latter group includes 35 families of uncharacterized proteins, which could also be involved in photosynthesis. Only a few components of cyanobacterial photosynthetic machinery are represented in the genomes of the anoxygenic phototrophic bacteria Chlorobium tepidum, Rhodopseudomonas palustris, Chloroflexus aurantiacus, or Heliobacillus mobilis. These observations, coupled with recent geological data on the properties of the ancient phototrophs, suggest that photosynthesis originated in the cyanobacterial lineage under the selective pressures of UV light and depletion of electron donors. We propose that the first phototrophs were anaerobic ancestors of cyanobacteria ("procyanobacteria") that conducted anoxygenic photosynthesis using a photosystem I-like reaction center, somewhat similar to the heterocysts of modern filamentous cyanobacteria. From procyanobacteria, photosynthesis spread to other phyla by way of lateral gene transfer.

Bacterial Proteins↗

PubMed2006

Unifying measures of gene function and evolution.

Recent genome analyses revealed intriguing correlations between variables characterizing the functioning of a gene, such as expression level (EL), connectivity of genetic and protein-protein interaction networks, and knockout effect, and variables describing gene evolution, such as sequence evolution rate (ER) and propensity for gene loss. Typically, variables within each of these classes are positively correlated, e.g. products of highly expressed genes also have a propensity to be involved in many protein-protein interactions, whereas variables between classes are negatively correlated, e.g. highly expressed genes, on average, evolve slower than weakly expressed genes. Here, we describe principal component (PC) analysis of seven genome-related variables and propose biological interpretations for the first three PCs. The first PC reflects a gene's 'importance', or the 'status' of a gene in the genomic community, with positive contributions from knockout lethality, EL, number of protein-protein interaction partners and the number of paralogues, and negative contributions from sequence ER and gene loss propensity. The next two PCs define a plane that seems to reflect the functional and evolutionary plasticity of a gene. Specifically, PC2 can be interpreted as a gene's 'adaptability' whereby genes with high adaptability readily duplicate, have many genetic interaction partners and tend to be non-essential. PC3 also might reflect the role of a gene in organismal adaptation albeit with a negative rather than a positive contribution of genetic interactions; we provisionally designate this PC 'reactivity'. The interpretation of PC2 and PC3 as measures of a gene's plasticity is compatible with the observation that genes with high values of these PCs tend to be expressed in a condition- or tissue-specific manner. Functional classes of genes substantially vary in status, adaptability and reactivity, with the highest status characteristic of the translation system and cytoskeletal proteins, highest adaptability seen in cellular processes and signalling genes, and top reactivity characteristic of metabolic enzymes.

Animals↗

PubMed2006

Coping with the quantitative genomics 'elephant': the correlation between the gene dispensability and evolution rate.

Early studies suggested that proteins with a greater contribution to the fitness of an organism evolve more slowly than less 'important' proteins. Recent articles by two research groups highlight the long-standing controversy about the genome-wide relationships between the measures of evolution rate, protein abundance and the fitness effect of gene disruption. These studies highlight the need for truly multidimensional approaches to the issues of quantitative genomics.

Animals↗

PubMed2006

A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action.

BACKGROUND: All archaeal and many bacterial genomes contain Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and variable arrays of the CRISPR-associated (cas) genes that have been previously implicated in a novel form of DNA repair on the basis of comparative analysis of their protein product sequences. However, the proximity of CRISPR and cas genes strongly suggests that they have related functions which is hard to reconcile with the repair hypothesis. RESULTS: The protein sequences of the numerous cas gene products were classified into approximately 25 distinct protein families; several new functional and structural predictions are described. Comparative-genomic analysis of CRISPR and cas genes leads to the hypothesis that the CRISPR-Cas system (CASS) is a mechanism of defense against invading phages and plasmids that functions analogously to the eukaryotic RNA interference (RNAi) systems. Specific functional analogies are drawn between several components of CASS and proteins involved in eukaryotic RNAi, including the double-stranded RNA-specific helicase-nuclease (dicer), the endonuclease cleaving target mRNAs (slicer), and the RNA-dependent RNA polymerase. However, none of the CASS components is orthologous to its apparent eukaryotic functional counterpart. It is proposed that unique inserts of CRISPR, some of which are homologous to fragments of bacteriophage and plasmid genes, function as prokaryotic siRNAs (psiRNA), by base-pairing with the target mRNAs and promoting their degradation or translation shutdown. Specific hypothetical schemes are developed for the functioning of the predicted prokaryotic siRNA system and for the formation of new CRISPR units with unique inserts encoding psiRNA conferring immunity to the respective newly encountered phages or plasmids. The unique inserts in CRISPR show virtually no similarity even between closely related bacterial strains which suggests their rapid turnover, on evolutionary scale. Corollaries of this finding are that, even among closely related prokaryotes, the most commonly encountered phages and plasmids are different and/or that the dominant phages and plasmids turn over rapidly. CONCLUSION: We proposed previously that Cas proteins comprise a novel DNA repair system. The association of the cas genes with CRISPR and, especially, the presence, in CRISPR units, of unique inserts homologous to phage and plasmid genes make us abandon this hypothesis. It appears most likely that CASS is a prokaryotic system of defense against phages and plasmids that functions via the RNAi mechanism. The functioning of this system seems to involve integration of fragments of foreign genes into archaeal and bacterial chromosomes yielding heritable immunity to the respective agents. However, it appears that this inheritance is extremely unstable on the evolutionary scale such that the repertoires of unique psiRNAs are completely replaced even in closely related prokaryotes, presumably, in response to rapidly changing repertoires of dominant phages and plasmids.

Journal Article↗

PubMed2005

Evolutionary plasticity of protein families: coupling between sequence and structure variation.

In this work we examine how protein structural changes are coupled with sequence variation in the course of evolution of a family of homologs. The sequence-structure correlation analysis performed on 81 homologous protein families shows that the majority of them exhibit statistically significant linear correlation between the measures of sequence and structural similarity. We observed, however, that there are cases where structural variability cannot be mainly explained by sequence variation, such as protein families with a number of disulfide bonds. To understand whether structures from different families and/or folds evolve in the same manner, we compared the degrees of structural change per unit of sequence change ("the evolutionary plasticity of structure") between those families with a significant linear correlation. Using rigorous statistical procedures we find that, with a few exceptions, evolutionary plasticity does not show a statistically significant difference between protein families. Similar sequence-structure analysis performed for protein loop regions shows that evolutionary plasticity of loop regions is greater than for the protein core.

Amino Acids↗

PubMed2005

Comparative genomics of Thermus thermophilus and Deinococcus radiodurans: divergent routes of adaptation to thermophily and radiation resistance.

BACKGROUND: Thermus thermophilus and Deinococcus radiodurans belong to a distinct bacterial clade but have remarkably different phenotypes. T. thermophilus is a thermophile, which is relatively sensitive to ionizing radiation and desiccation, whereas D. radiodurans is a mesophile, which is highly radiation- and desiccation-resistant. Here we present an in-depth comparison of the genomes of these two related but differently adapted bacteria. RESULTS: By reconstructing the evolution of Thermus and Deinococcus after the divergence from their common ancestor, we demonstrate a high level of post-divergence gene flux in both lineages. Various aspects of the adaptation to high temperature in Thermus can be attributed to horizontal gene transfer from archaea and thermophilic bacteria; many of the horizontally transferred genes are located on the single megaplasmid of Thermus. In addition, the Thermus lineage has lost a set of genes that are still present in Deinococcus and many other mesophilic bacteria but are not common among thermophiles. By contrast, Deinococcus seems to have acquired numerous genes related to stress response systems from various bacteria. A comparison of the distribution of orthologous genes among the four partitions of the Deinococcus genome and the two partitions of the Thermus genome reveals homology between the Thermus megaplasmid (pTT27) and Deinococcus megaplasmid (DR177). CONCLUSION: After the radiation from their common ancestor, the Thermus and Deinococcus lineages have taken divergent paths toward their distinct lifestyles. In addition to extensive gene loss, Thermus seems to have acquired numerous genes from thermophiles, which likely was the decisive contribution to its thermophilic adaptation. By contrast, Deinococcus lost few genes but seems to have acquired many bacterial genes that apparently enhanced its ability to survive different kinds of environmental stresses. Notwithstanding the accumulation of horizontally transferred genes, we also show that the single megaplasmid of Thermus and the DR177 megaplasmid of Deinococcus are homologous and probably were inherited from the common ancestor of these bacteria.

Acclimatization↗

PubMed2005

Ancestral paralogs and pseudoparalogs and their role in the emergence of the eukaryotic cell.

Gene duplication is a crucial mechanism of evolutionary innovation. A substantial fraction of eukaryotic genomes consists of paralogous gene families. We assess the extent of ancestral paralogy, which dates back to the last common ancestor of all eukaryotes, and examine the origins of the ancestral paralogs and their potential roles in the emergence of the eukaryotic cell complexity. A parsimonious reconstruction of ancestral gene repertoires shows that 4137 orthologous gene sets in the last eukaryotic common ancestor (LECA) map back to 2150 orthologous sets in the hypothetical first eukaryotic common ancestor (FECA) [paralogy quotient (PQ) of 1.92]. Analogous reconstructions show significantly lower levels of paralogy in prokaryotes, 1.19 for archaea and 1.25 for bacteria. The only functional class of eukaryotic proteins with a significant excess of paralogous clusters over the mean includes molecular chaperones and proteins with related functions. Almost all genes in this category underwent multiple duplications during early eukaryotic evolution. In structural terms, the most prominent sets of paralogs are superstructure-forming proteins with repetitive domains, such as WD-40 and TPR. In addition to the true ancestral paralogs which evolved via duplication at the onset of eukaryotic evolution, numerous pseudoparalogs were detected, i.e. homologous genes that apparently were acquired by early eukaryotes via different routes, including horizontal gene transfer (HGT) from diverse bacteria. The results of this study demonstrate a major increase in the level of gene paralogy as a hallmark of the early evolution of eukaryotes.

Amino Acid Sequence↗

PubMed2005

A universal trend of amino acid gain and loss in protein evolution.

Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. For example, proteins from organisms with (G + C)-rich (or (A + T)-rich) genomes contain more (or fewer) amino acids encoded by (G + C)-rich codons. However, no universal trends in ongoing changes of amino acid frequencies have been reported. We compared sets of orthologous proteins encoded by triplets of closely related genomes from 15 taxa representing all three domains of life (Bacteria, Archaea and Eukaryota), and used phylogenies to polarize amino acid substitutions. Cys, Met, His, Ser and Phe accrue in at least 14 taxa, whereas Pro, Ala, Glu and Gly are consistently lost. The same nine amino acids are currently accrued or lost in human proteins, as shown by analysis of non-synonymous single-nucleotide polymorphisms. All amino acids with declining frequencies are thought to be among the first incorporated into the genetic code; conversely, all amino acids with increasing frequencies, except Ser, were probably recruited late. Thus, expansion of initially under-represented amino acids, which began over 3,400 million years ago, apparently continues to this day.

AT Rich Sequence↗

PubMed2004

Genome sequence of the deep-sea gamma-proteobacterium Idiomarina loihiensis reveals amino acid fermentation as a source of carbon and energy.

We report the complete genome sequence of the deep-sea gamma-proteobacterium, Idiomarina loihiensis, isolated recently from a hydrothermal vent at 1,300-m depth on the Loihi submarine volcano, Hawaii. The I. loihiensis genome comprises a single chromosome of 2,839,318 base pairs, encoding 2,640 proteins, four rRNA operons, and 56 tRNA genes. A comparison of I. loihiensis to the genomes of other gamma-proteobacteria reveals abundance of amino acid transport and degradation enzymes, but a loss of sugar transport systems and certain enzymes of sugar metabolism. This finding suggests that I. loihiensis relies primarily on amino acid catabolism, rather than on sugar fermentation, for carbon and energy. Enzymes for biosynthesis of purines, pyrimidines, the majority of amino acids, and coenzymes are encoded in the genome, but biosynthetic pathways for Leu, Ile, Val, Thr, and Met are incomplete. Auxotrophy for Val and Thr was confirmed by in vivo experiments. The I. loihiensis genome contains a cluster of 32 genes encoding enzymes for exopolysaccharide and capsular polysaccharide synthesis. It also encodes diverse peptidases, a variety of peptide and amino acid uptake systems, and versatile signal transduction machinery. We propose that the source of amino acids for I. loihiensis growth are the proteinaceous particles present in the deep sea hydrothermal vent waters. I. loihiensis would colonize these particles by using the secreted exopolysaccharide, digest these proteins, and metabolize the resulting peptides and amino acids. In summary, the I. loihiensis genome reveals an integrated mechanism of metabolic adaptation to the constantly changing deep-sea hydrothermal ecosystem.

Amino Acids↗

PubMed2004

Gene family evolution: an in-depth theoretical and simulation analysis of non-linear birth-death-innovation models.

BACKGROUND: The size distribution of gene families in a broad range of genomes is well approximated by a generalized Pareto function. Evolution of ensembles of gene families can be described with Birth, Death, and Innovation Models (BDIMs). Analysis of the properties of different versions of BDIMs has the potential of revealing important features of genome evolution. RESULTS: In this work, we extend our previous analysis of stochastic BDIMs. In addition to the previously examined rational BDIMs, we introduce potentially more realistic logistic BDIMs, in which birth/death rates are limited for the largest families, and show that their properties are similar to those of models that include no such limitation. We show that the mean time required for the formation of the largest gene families detected in eukaryotic genomes is limited by the mean number of duplications per gene and does not increase indefinitely with the model degree. Instead, this time reaches a minimum value, which corresponds to a non-linear rational BDIM with the degree of approximately 2.7. Even for this BDIM, the mean time of the largest family formation is orders of magnitude greater than any realistic estimates based on the timescale of life's evolution. We employed the embedding chains technique to estimate the expected number of elementary evolutionary events (gene duplications and deletions) preceding the formation of gene families of the observed size and found that the mean number of events exceeds the family size by orders of magnitude, suggesting a highly dynamic process of genome evolution. The variance of the time required for the formation of the largest families was found to be extremely large, with the coefficient of variation >> 1. This indicates that some gene families might grow much faster than the mean rate such that the minimal time required for family formation is more relevant for a realistic representation of genome evolution than the mean time. We determined this minimal time using Monte Carlo simulations of family growth from an ensemble of simultaneously evolving singletons. In these simulations, the time elapsed before the formation of the largest family was much shorter than the estimated mean time and was compatible with the timescale of evolution of eukaryotes. CONCLUSIONS: The analysis of stochastic BDIMs presented here shows that non-linear versions of such models can well approximate not only the size distribution of gene families but also the dynamics of their formation during genome evolution. The fact that only higher degree BDIMs are compatible with the observed characteristics of genome evolution suggests that the growth of gene families is self-accelerating, which might reflect differential selective pressure acting on different genes.

Birth Rate↗

PubMed2004

Conservation and coevolution in the scale-free human gene coexpression network.

The role of natural selection in biology is well appreciated. Recently, however, a critical role for physical principles of network self-organization in biological systems has been revealed. Here, we employ a systems level view of genome-scale sequence and expression data to examine the interplay between these two sources of order, natural selection and physical self-organization, in the evolution of human gene regulation. The topology of a human gene coexpression network, derived from tissue-specific expression profiles, shows scale-free properties that imply evolutionary self-organization via preferential node attachment. Genes with numerous coexpressed partners (the hubs of the coexpression network) evolve more slowly on average than genes with fewer coexpressed partners, and genes that are coexpressed show similar rates of evolution. Thus, the strength of selective constraints on gene sequences is affected by the topology of the gene coexpression network. This connection is strong for the coding regions and 3' untranslated regions (UTRs), but the 5' UTRs appear to evolve under a different regime. Surprisingly, we found no connection between the rate of gene sequence divergence and the extent of gene expression profile divergence between human and mouse. This suggests that distinct modes of natural selection might govern sequence versus expression divergence, and we propose a model, based on rapid, adaptation-driven divergence and convergent evolution of gene expression patterns, for how natural selection could influence gene expression divergence.

3' Untranslated Regions↗

PubMed2004

Duplicated genes evolve slower than singletons despite the initial rate increase.

BACKGROUND: Gene duplication is an important mechanism that can lead to the emergence of new functions during evolution. The impact of duplication on the mode of gene evolution has been the subject of several theoretical and empirical comparative-genomic studies. It has been shown that, shortly after the duplication, genes seem to experience a considerable relaxation of purifying selection. RESULTS: Here we demonstrate two opposite effects of gene duplication on evolutionary rates. Sequence comparisons between paralogs show that, in accord with previous observations, a substantial acceleration in the evolution of paralogs occurs after duplication, presumably due to relaxation of purifying selection. The effect of gene duplication on evolutionary rate was also assessed by sequence comparison between orthologs that have paralogs (duplicates) and those that do not (singletons). It is shown that, in eukaryotes, duplicates, on average, evolve significantly slower than singletons. Eukaryotic ortholog evolutionary rates for duplicates are also negatively correlated with the number of paralogs per gene and the strength of selection between paralogs. A tally of annotated gene functions shows that duplicates tend to be enriched for proteins with known functions, particularly those involved in signaling and related cellular processes; by contrast, singletons include an over-abundance of poorly characterized proteins. CONCLUSIONS: These results suggest that whether or not a gene duplicate is retained by selection depends critically on the pre-existing functional utility of the protein encoded by the ancestral singleton. Duplicates of genes of a higher biological import, which are subject to strong functional constraints on the sequence, are retained relatively more often. Thus, the evolutionary trajectory of duplicated genes appears to be determined by two opposing trends, namely, the post-duplication rate acceleration and the generally slow evolutionary rate owing to the high level of functional constraints.

Animals↗

PubMed2004

A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes.

BACKGROUND: Sequencing the genomes of multiple, taxonomically diverse eukaryotes enables in-depth comparative-genomic analysis which is expected to help in reconstructing ancestral eukaryotic genomes and major events in eukaryotic evolution and in making functional predictions for currently uncharacterized conserved genes. RESULTS: We examined functional and evolutionary patterns in the recently constructed set of 5,873 clusters of predicted orthologs (eukaryotic orthologous groups or KOGs) from seven eukaryotic genomes: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe and Encephalitozoon cuniculi. Conservation of KOGs through the phyletic range of eukaryotes strongly correlates with their functions and with the effect of gene knockout on the organism's viability. The approximately 40% of KOGs that are represented in six or seven species are enriched in proteins responsible for housekeeping functions, particularly translation and RNA processing. These conserved KOGs are often essential for survival and might approximate the minimal set of essential eukaryotic genes. The 131 single-member, pan-eukaryotic KOGs we identified were examined in detail. For around 20 that remained uncharacterized, functions were predicted by in-depth sequence analysis and examination of genomic context. Nearly all these proteins are subunits of known or predicted multiprotein complexes, in agreement with the balance hypothesis of evolution of gene copy number. Other KOGs show a variety of phyletic patterns, which points to major contributions of lineage-specific gene loss and the 'invention' of genes new to eukaryotic evolution. Examination of the sets of KOGs lost in individual lineages reveals co-elimination of functionally connected genes. Parsimonious scenarios of eukaryotic genome evolution and gene sets for ancestral eukaryotic forms were reconstructed. The gene set of the last common ancestor of the crown group consists of 3,413 KOGs and largely includes proteins involved in genome replication and expression, and central metabolism. Only 44% of the KOGs, mostly from the reconstructed gene set of the last common ancestor of the crown group, have detectable homologs in prokaryotes; the remainder apparently evolved via duplication with divergence and invention of new genes. CONCLUSIONS: The KOG analysis reveals a conserved core of largely essential eukaryotic genes as well as major diversification and innovation associated with evolution of eukaryotic genomes. The results provide quantitative support for major trends of eukaryotic evolution noticed previously at the qualitative level and a basis for detailed reconstruction of evolution of eukaryotic genomes and biology of ancestral forms.

Animals↗

PubMed2004

Computational approaches for the analysis of gene neighbourhoods in prokaryotic genomes.

Gene order in prokaryotes is conserved to a much lesser extent than protein sequences. Only some operons, primarily those that encode physically interacting proteins, are conserved in all or most of the bacterial and archaeal genomes. Nevertheless, even the limited conservation of operon organisation that is observed provides valuable evolutionary and functional clues through multiple genome comparisons. With the rapid growth in the number and diversity of sequenced prokaryotic genomes, functional inferences for uncharacterized genes located in the same conserved gene neighborhood with well-studied genes are becoming increasingly important. In this review, we discuss various computational approaches for identification of conserved gene strings and construction of local alignments of gene orders in prokaryotic genomes.

Algorithms↗

PubMed2004

Coelomata and not Ecdysozoa: evidence from genome-wide phylogenetic analysis.

Relative positions of nematodes, arthropods, and chordates in animal phylogeny remain uncertain. The traditional tree topology joins arthropods with chordates in a coelomate clade, whereas nematodes, which lack a coelome, occupy a basal position. However, the current leading hypothesis, based on phylogenetic trees for 18S ribosomal RNA and several proteins, joins nematodes with arthropods in a clade of molting animals, Ecdysozoa. We performed a phylogenetic analysis of over 500 sets of orthologous proteins, which are represented in plants, animals, and fungi, using maximum likelihood, maximum parsimony, and distance methods. Additionally, to increase the statistical power of topology tests, the same methods were applied to concatenated alignments of subunits of eight conserved macromolecular complexes. The majority of the methods, when applied to most of the orthologous clusters, both concatenated and individual, grouped the fly with humans to the exclusion of the nematode, in support of the coelomate phylogeny. Trees were also constructed using information on insertions and deletions in orthologous proteins, combinations of domains in multidomain proteins, and presence-absence of species in clusters of orthologs. All of these approaches supported the coelomate clade and showed concordance between evolution of protein sequences and higher-level evolutionary events, such as domain fusion or gene loss.

Animals↗