Showing papers on "Genome published in 2005"
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TL;DR: A comprehensive search for conserved elements in vertebrate genomes is conducted, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes), using a two-state phylogenetic hidden Markov model (phylo-HMM).
Abstract: We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes). Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model (phylo-HMM). PhastCons works by fitting a phylo-HMM to the data by maximum likelihood, subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based on this model. The predicted elements cover roughly 3%-8% of the human genome (depending on the details of the calibration procedure) and substantially higher fractions of the more compact Drosophila melanogaster (37%-53%), Caenorhabditis elegans (18%-37%), and Saccharaomyces cerevisiae (47%-68%) genomes. From yeasts to vertebrates, in order of increasing genome size and general biological complexity, increasing fractions of conserved bases are found to lie outside of the exons of known protein-coding genes. In all groups, the most highly conserved elements (HCEs), by log-odds score, are hundreds or thousands of bases long. These elements share certain properties with ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories. In vertebrates, HCEs are associated with the 3' UTRs of regulatory genes, stable gene deserts, and megabase-sized regions rich in moderately conserved noncoding sequences. Noncoding HCEs also show strong statistical evidence of an enrichment for RNA secondary structure.
3,719 citations
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TL;DR: A map-based, finished quality sequence that covers 95% of the 389 Mb rice genome, including virtually all of the euchromatin and two complete centromeres, and finds evidence for widespread and recurrent gene transfer from the organelles to the nuclear chromosomes.
Abstract: Rice, one of the world's most important food plants, has important syntenic relationships with the other cereal species and is a model plant for the grasses. Here we present a map-based, finished quality sequence that covers 95% of the 389 Mb genome, including virtually all of the euchromatin and two complete centromeres. A total of 37,544 non-transposable-element-related protein-coding genes were identified, of which 71% had a putative homologue in Arabidopsis. In a reciprocal analysis, 90% of the Arabidopsis proteins had a putative homologue in the predicted rice proteome. Twenty-nine per cent of the 37,544 predicted genes appear in clustered gene families. The number and classes of transposable elements found in the rice genome are consistent with the expansion of syntenic regions in the maize and sorghum genomes. We find evidence for widespread and recurrent gene transfer from the organelles to the nuclear chromosomes. The map-based sequence has proven useful for the identification of genes underlying agronomic traits. The additional single-nucleotide polymorphisms and simple sequence repeats identified in our study should accelerate improvements in rice production.
3,423 citations
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TL;DR: Detailed polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
Abstract: This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
3,412 citations
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TL;DR: Hundreds of Arabidopsis genes were found that outperform traditional reference genes in terms of expression stability throughout development and under a range of environmental conditions, and the developed PCR primers or hybridization probes for the novel reference genes will enable better normalization and quantification of transcript levels inArabidopsis in the future.
Abstract: Gene transcripts with invariant abundance during development and in the face of environmental stimuli are essential reference points for accurate gene expression analyses, such as RNA gel-blot analysis or quantitative reverse transcription-polymerase chain reaction (PCR). An exceptionally large set of data from Affymetrix ATH1 whole-genome GeneChip studies provided the means to identify a new generation of reference genes with very stable expression levels in the model plant species Arabidopsis (Arabidopsis thaliana). Hundreds of Arabidopsis genes were found that outperform traditional reference genes in terms of expression stability throughout development and under a range of environmental conditions. Most of these were expressed at much lower levels than traditional reference genes, making them very suitable for normalization of gene expression over a wide range of transcript levels. Specific and efficient primers were developed for 22 genes and tested on a diverse set of 20 cDNA samples. Quantitative reverse transcription-PCR confirmed superior expression stability and lower absolute expression levels for many of these genes, including genes encoding a protein phosphatase 2A subunit, a coatomer subunit, and an ubiquitin-conjugating enzyme. The developed PCR primers or hybridization probes for the novel reference genes will enable better normalization and quantification of transcript levels in Arabidopsis in the future.
2,694 citations
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TL;DR: A KO-Based Annotation System (KOBAS) is developed that can automatically annotate a set of sequences with KO terms and identify both the most frequent and the statistically significantly enriched pathways.
Abstract: Motivation: High-throughput technologies such as DNA sequencing and microarrays have created the need for automated annotation of large sets of genes, including whole genomes, and automated identification of pathways. Ontologies, such as the popular Gene Ontology (GO), provide a common controlled vocabulary for these types of automated analysis. Yet, while GO offers tremendous value, it also has certain limitations such as the lack of direct association with pathways.
Results: We demonstrated the use of the KEGG Orthology (KO), part of the KEGG suite of resources, as an alternative controlled vocabulary for automated annotation and pathway identification. We developed a KO-Based Annotation System (KOBAS) that can automatically annotate a set of sequences with KO terms and identify both the most frequent and the statistically significantly enriched pathways. Results from both whole genome and microarray gene cluster annotations with KOBAS are comparable and complementary to known annotations. KOBAS is a freely available standalone Python program that can contribute significantly to genome annotation and microarray analysis.
Availability: Supplementary data and the KOBAS system are available at http://genome.cbi.pku.edu.cn/download.html
Contact: weilp@mail.cbi.pku.edu.cn
2,595 citations
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Kerstin Lindblad-Toh1, Claire M. Wade1, Claire M. Wade2, Tarjei S. Mikkelsen3 +238 more•Institutions (11)
TL;DR: A high-quality draft genome sequence of the domestic dog is reported, together with a dense map of single nucleotide polymorphisms (SNPs) across breeds, to shed light on the structure and evolution of genomes and genes.
Abstract: Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
2,431 citations
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TL;DR: It is found that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles.
Abstract: Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differenc ...
2,267 citations
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TL;DR: The genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans, was generated and Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactic pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
Abstract: The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for ≈80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
2,092 citations
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TL;DR: An interactive system, Galaxy, that combines the power of existing genome annotation databases with a simple Web portal to enable users to search remote resources, combine data from independent queries, and visualize the results.
Abstract: Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the power of existing genome annotation databases with a simple Web portal to enable users to search remote resources, combine data from independent queries, and visualize the results. The heart of Galaxy is a flexible history system that stores the queries from each user; performs operations such as intersections, unions, and subtractions; and links to other computational tools. Galaxy can be accessed at http://g2.bx.psu.edu.
2,071 citations
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TL;DR: In this article, a comparative analysis of the human, mouse, rat and dog genomes is presented to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs).
Abstract: Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs). The promoter analysis yields 174 candidate motifs, including most previously known transcription-factor binding sites and 105 new motifs. The 3'-UTR analysis yields 106 motifs likely to be involved in post-transcriptional regulation. Nearly one-half are associated with microRNAs (miRNAs), leading to the discovery of many new miRNA genes and their likely target genes. Our results suggest that previous estimates of the number of human miRNA genes were low, and that miRNAs regulate at least 20% of human genes. The overall results provide a systematic view of gene regulation in the human, which will be refined as additional mammalian genomes become available.
1,954 citations
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TL;DR: The average nucleotide identity of the shared genes between two strains was found to be a robust means to compare genetic relatedness among strains, and that ANI values of approximately 94% corresponded to the traditional 70% DNA-DNA reassociation standard of the current species definition.
Abstract: To help advance the species definition for prokaryotes, we have compared the gene content of 70 closely related and fully sequenced bacterial genomes to identify whether species boundaries exist, and to determine the role of the organism's ecology on its shared gene content. We found the average nucleotide identity (ANI) of the shared genes between two strains to be a robust means to compare genetic relatedness among strains, and that ANI values of ≈94% corresponded to the traditional 70% DNA–DNA reassociation standard of the current species definition. At the 94% ANI cutoff, current species includes only moderately homogeneous strains, e.g., most of the >4-Mb genomes share only 65–90% of their genes, apparently as a result of the strains having evolved in different ecological settings. Furthermore, diagnostic genetic signatures (boundaries) are evident between groups of strains of the same species, and the intergroup genetic similarity can be as high as 98–99% ANI, indicating that justifiable species might be found even among organisms that are nearly identical at the nucleotide level. Notably, a large fraction, e.g., up to 65%, of the differences in gene content within species is associated with bacteriophage and transposase elements, revealing an important role of these elements during bacterial speciation. Our findings are consistent with a definition for species that would include a more homogeneous set of strains than provided by the current definition and one that considers the ecology of the strains in addition to their evolutionary distance.
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Wellcome Trust Sanger Institute1, George Washington University2, J. Craig Venter Institute3, University of Glasgow4, University of Oxford5, Newcastle University6, University of Bordeaux7, University of Cambridge8, Oregon Health & Science University9, University of Dundee10, Imperial College London11, Case Western Reserve University12, Yale University13, Université catholique de Louvain14, University of Iowa15, Wellcome Trust16
TL;DR: Comparisons of the cytoskeleton and endocytic trafficking systems of Trypanosoma brucei with those of humans and other eukaryotic organisms reveal major differences.
Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
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TL;DR: A new method for de novo identification of repeat families via extension of consensus seeds is developed, which enables a rigorous definition of repeat boundaries, a key issue in repeat analysis.
Abstract: Every time we compare two species that are closer to each other than either is to humans, we get nearly killed by unmasked repeats.
Webb Miller (Personal communication)
Motivation:De novo repeat family identification is a challenging algorithmic problem of great practical importance. As the number of genome sequencing projects increases, there is a pressing need to identify the repeat families present in large, newly sequenced genomes. We develop a new method for de novo identification of repeat families via extension of consensus seeds; our method enables a rigorous definition of repeat boundaries, a key issue in repeat analysis.
Results: Our RepeatScout algorithm is more sensitive and is orders of magnitude faster than RECON, the dominant tool for de novo repeat family identification in newly sequenced genomes. Using RepeatScout, we estimate that ∼2% of the human genome and 4% of mouse and rat genomes consist of previously unannotated repetitive sequence.
Availability: Source code is available for download at http://www-cse.ucsd.edu/groups/bioinformatics/software.html
Contact: ppevzner@cs.ucsd.edu
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TL;DR: The draft sequence of the M. grisea genome is reported, reflecting the clonal nature of this fungus imposed by widespread rice cultivation and analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease.
Abstract: Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.
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TL;DR: The sequencing and mapping of the human genome provides a foundation for the elucidation of gene expression and protein function, and the identification of the biochemical pathways implicated in the natural history of chronic diseases.
Abstract: The sequencing and mapping of the human genome provides a foundation for the elucidation of gene expression and protein function, and the identification of the biochemical pathways implicated in the natural history of chronic diseases, including cancer, diabetes, and vascular and neurodegenerative
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TL;DR: Questions are addressed, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
Abstract: Much of natural product chemistry concerns a group of compounds known as secondary metabolites. These low-molecular-weight metabolites often have potent physiological activities. Digitalis, morphine and quinine are plant secondary metabolites, whereas penicillin, cephalosporin, ergotrate and the statins are equally well known fungal secondary metabolites. Although chemically diverse, all secondary metabolites are produced by a few common biosynthetic pathways, often in conjunction with morphological development. Recent advances in molecular biology, bioinformatics and comparative genomics have revealed that the genes encoding specific fungal secondary metabolites are clustered and often located near telomeres. In this review, we address some important questions, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
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TL;DR: The reconstruction of regulatory networks from expression profiles of human B cells is reported, suggestive of a hierarchical, scale-free network, where a few highly interconnected genes (hubs) account for most of the interactions.
Abstract: Cellular phenotypes are determined by the differential activity of networks linking coregulated genes. Available methods for the reverse engineering of such networks from genome-wide expression profiles have been successful only in the analysis of lower eukaryotes with simple genomes. Using a new method called ARACNe (algorithm for the reconstruction of accurate cellular networks), we report the reconstruction of regulatory networks from expression profiles of human B cells. The results are suggestive a hierarchical, scale-free network, where a few highly interconnected genes (hubs) account for most of the interactions. Validation of the network against available data led to the identification of MYC as a major hub, which controls a network comprising known target genes as well as new ones, which were biochemically validated. The newly identified MYC targets include some major hubs. This approach can be generally useful for the analysis of normal and pathologic networks in mammalian cells.
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TL;DR: The hypothesis that the relatively large and complex vertebrate genome was created by two ancient, whole genome duplications has been hotly debated, and the potential for these large-scale genomic events to have driven the evolutionary success of the vertebrate lineage is highlighted.
Abstract: The hypothesis that the relatively large and complex vertebrate genome was created by two ancient, whole genome duplications has been hotly debated, but remains unresolved. We reconstructed the evolutionary relationships of all gene families from the complete gene sets of a tunicate, fish, mouse, and human, and then determined when each gene duplicated relative to the evolutionary tree of the organisms. We confirmed the results of earlier studies that there remains little signal of these events in numbers of duplicated genes, gene tree topology, or the number of genes per multigene family. However, when we plotted the genomic map positions of only the subset of paralogous genes that were duplicated prior to the fish–tetrapod split, their global physical organization provides unmistakable evidence of two distinct genome duplication events early in vertebrate evolution indicated by clear patterns of four-way paralogous regions covering a large part of the human genome. Our results highlight the potential for these large-scale genomic events to have driven the evolutionary success of the vertebrate lineage.
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Wellcome Trust Sanger Institute1, Seattle Biomed2, Katholieke Universiteit Leuven3, GATC Biotech4, Max Planck Society5, Washington University in St. Louis6, University of Trieste7, International Centre for Genetic Engineering and Biotechnology8, European Bioinformatics Institute9, University of São Paulo10, National Scientific and Technical Research Council11, Université catholique de Louvain12, University of London13, University of Edinburgh14, University of Glasgow15, University of Wisconsin-Madison16, University of York17, University of Cambridge18, University of Washington19
TL;DR: The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Tritryp genomes suggest that the mechanisms regulating RNA polymerase II–directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling.
Abstract: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
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George Washington University1, Seattle Biomed2, University of Washington3, J. Craig Venter Institute4, Karolinska Institutet5, University of California, Los Angeles6, Universidade Federal de Minas Gerais7, Uppsala University8, Centre national de la recherche scientifique9, University of Glasgow10, University of Cambridge11, Federal University of São Paulo12, Children's Hospital Oakland Research Institute13, Johns Hopkins University School of Medicine14, National Research Council15, University of Oxford16, University of London17, University of Massachusetts Amherst18, Oswaldo Cruz Foundation19, University of Buenos Aires20, Central University of Venezuela21, National University of Singapore22, University of Georgia23
TL;DR: Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Abstract: Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
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TL;DR: A number of elements in this region that have undergone intense purifying selection throughout mammalian evolution are described, and it is shown that these important elements are more numerous than previously thought.
Abstract: Comparisons of orthologous genomic DNA sequences can be used to characterize regions that have been subject to purifying selection and are enriched for functional elements. We here present the results of such an analysis on an alignment of sequences from 29 mammalian species. The alignment captures ∼3.9 neutral substitutions per site and spans ∼1.9 Mbp of the human genome. We identify constrained elements from 3 bp to over 1 kbp in length, covering ∼5.5% of the human locus. Our estimate for the total amount of nonexonic constraint experienced by this locus is roughly twice that for exonic constraint. Constrained elements tend to cluster, and we identify large constrained regions that correspond well with known functional elements. While constraint density inversely correlates with mobile element density, we also show the presence of unambiguously constrained elements overlapping mammalian ancestral repeats. In addition, we describe a number of elements in this region that have undergone intense purifying selection throughout mammalian evolution, and we show that these important elements are more numerous than previously thought. These results were obtained with Genomic Evolutionary Rate Profiling (GERP), a statistically rigorous and biologically transparent framework for constrained element identification. GERP identifies regions at high resolution that exhibit nucleotide substitution deficits, and measures these deficits as “rejected substitutions.” Rejected substitutions reflect the intensity of past purifying selection and are used to rank and characterize constrained elements. We anticipate that GERP and the types of analyses it facilitates will provide further insights and improved annotation for the human genome as mammalian genome sequence data become richer.
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Broad Institute1, J. Craig Venter Institute2, Stanford University3, Oregon Health & Science University4, University of Glasgow5, Genetic Information Research Institute6, Institut Universitaire de France7, University of Kentucky8, University of Nebraska–Lincoln9, University of Göttingen10, Pasteur Institute11, University of São Paulo12, Texas A&M University13, Wellcome Trust Sanger Institute14, John Innes Centre15, University of Wisconsin-Madison16, Max Planck Society17, University of Oregon18, University of Nottingham19, Spanish National Research Council20, Ohio State University21, University of Georgia22, Tokyo Institute of Technology23, National Institute of Advanced Industrial Science and Technology24, George Washington University25, University of Manchester26, University of Liverpool27, University of Melbourne28, Karlsruhe Institute of Technology29, University of Idaho30
TL;DR: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution, and a comparative study with Aspergillus fumigatus and As pergillus oryzae, used in the production of sake, miso and soy sauce, provides new insight into eukaryotic genome evolution and gene regulation.
Abstract: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.
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University of Cologne1, Laboratory of Molecular Biology2, Wellcome Trust Sanger Institute3, Baylor College of Medicine4, University of California, San Diego5, Northwestern University6, University of Tsukuba7, Ludwig Maximilian University of Munich8, University of Cambridge9, Hokkaido University10, Pasteur Institute11, University of York12, National Institute of Genetics13, University of Tokyo14, Princeton University15, University of Dundee16
TL;DR: A proteome-based phylogeny shows that the amoebozoa diverged from the animal–fungal lineage after the plant–animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
Abstract: The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
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TL;DR: Evidence is now supported by evidence showing that genes that are retained in duplicate typically diversify in function or undergo subfunctionalization, with some duplicate genes more prone to retention than others.
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TL;DR: To identify other miRNA genes in pathogenic viruses, a new miRNA gene prediction method with small-RNA cloning from several virus-infected cell types was combined and predicted miRNAs in several large DNA viruses.
Abstract: Epstein-Barr virus (EBV or HHV4), a member of the human herpesvirus (HHV) family, has recently been shown to encode microRNAs (miRNAs). In contrast to most eukaryotic miRNAs, these viral miRNAs do not have close homologs in other viral genomes or in the genome of the human host. To identify other miRNA genes in pathogenic viruses, we combined a new miRNA gene prediction method with small-RNA cloning from several virus-infected cell types. We cloned ten miRNAs in the Kaposi sarcoma-associated virus (KSHV or HHV8), nine miRNAs in the mouse gammaherpesvirus 68 (MHV68) and nine miRNAs in the human cytomegalovirus (HCMV or HHV5). These miRNA genes are expressed individually or in clusters from either polymerase (pol) II or pol III promoters, and share no substantial sequence homology with one another or with the known human miRNAs. Generally, we predicted miRNAs in several large DNA viruses, and we could neither predict nor experimentally identify miRNAs in the genomes of small RNA viruses or retroviruses.
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TL;DR: The main factors — including models of the allelic architecture of common diseases, sample size, map density and sample-collection biases — that need to be taken into account in order to optimize the cost efficiency of identifying genuine disease-susceptibility loci are outlined.
Abstract: To fully understand the allelic variation that underlies common diseases, complete genome sequencing for many individuals with and without disease is required. This is still not technically feasible. However, recently it has become possible to carry out partial surveys of the genome by genotyping large numbers of common SNPs in genome-wide association studies. Here, we outline the main factors - including models of the allelic architecture of common diseases, sample size, map density and sample-collection biases - that need to be taken into account in order to optimize the cost efficiency of identifying genuine disease-susceptibility loci.
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TL;DR: The transcribed portions of the human genome are predominantly composed of interlaced networks of both poly A+ and poly A– annotated transcripts and unannotated transcripts of unknown function, which has important implications for interpreting genotype-phenotype associations, regulation of gene expression, and the definition of a gene.
Abstract: Sites of transcription of polyadenylated and nonpolyadenylated RNAs for 10 human chromosomes were mapped at 5-base pair resolution in eight cell lines. Unannotated, nonpolyadenylated transcripts comprise the major proportion of the transcriptional output of the human genome. Of all transcribed sequences, 19.4, 43.7, and 36.9% were observed to be polyadenylated, nonpolyadenylated, and bimorphic, respectively. Half of all transcribed sequences are found only in the nucleus and for the most part are unannotated. Overall, the transcribed portions of the human genome are predominantly composed of interlaced networks of both poly A+ and poly A- annotated transcripts and unannotated transcripts of unknown function. This organization has important implications for interpreting genotype-phenotype associations, regulation of gene expression, and the definition of a gene.
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TL;DR: Until around 1990, most multigene families were thought to be subject to concerted evolution, in which all member genes of a family evolve as a unit in concert, but phylogenetic analysis of MHC and other immune system genes showed a quite different evolutionary pattern, and a new model called birth-and-death evolution was proposed.
Abstract: Until around 1990, most multigene families were thought to be subject to concerted evolution, in which all member genes of a family evolve as a unit in concert. However, phylogenetic analysis of MHC and other immune system genes showed a quite different evolutionary pattern, and a new model called birth-and-death evolution was proposed. In this model, new genes are created by gene duplication and some duplicate genes stay in the genome for a long time, whereas others are inactivated or deleted from the genome. Later investigations have shown that most non-rRNA genes including highly conserved histone or ubiquitin genes are subject to this type of evolution. However, the controversy over the two models is still continuing because the distinction between the two models becomes difficult when sequence differences are small. Unlike concerted evolution, the model of birth-and-death evolution can give some insights into the origins of new genetic systems or new phenotypic characters.
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National Institute of Advanced Industrial Science and Technology1, National Institute of Technology and Evaluation2, Intec, Inc.3, Tohoku University4, University of Tokyo5, Nagoya University6, Tokyo University of Agriculture and Technology7, University of Manchester8, Broad Institute9, George Washington University10, Agricultural Research Service11, University of Nottingham12, Tulane University13, J. Craig Venter Institute14, Kikkoman15, Kyushu University16, Nara Institute of Science and Technology17
TL;DR: Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.
Abstract: The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.
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TL;DR: A high-resolution genetic map of the human genome is presented, based on statistical analyses of genetic variation data, and more than 25,000 recombination hotspots are identified, together with motifs and sequence contexts that play a role in hotspot activity.
Abstract: Genetic maps, which document the way in which recombination rates vary over a genome, are an essential tool for many genetic analyses. We present a high-resolution genetic map of the human genome, based on statistical analyses of genetic variation data, and identify more than 25,000 recombination hotspots, together with motifs and sequence contexts that play a role in hotspot activity. Differences between the behavior of recombination rates over large (megabase) and small (kilobase) scales lead us to suggest a two-stage model for recombination in which hotspots are stochastic features, within a framework in which large-scale rates are constrained.