Mobile elements: drivers of genome evolution.
12 Mar 2004-Science (American Association for the Advancement of Science)-Vol. 303, Iss: 5664, pp 1626-1632
TL;DR: Mobile elements within genomes have driven genome evolution in diverse ways and are becoming useful tools for learning more about genome evolution and gene function.
Abstract: Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and have shaped both genes and the entire genome. Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function.
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TL;DR: New insights have been gained into how silencing in eukaryotic cells has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome.
Abstract: Overlapping epigenetic mechanisms have evolved in eukaryotic cells to silence the expression and mobility of transposable elements (TEs). Owing to their ability to recruit the silencing machinery, TEs have served as building blocks for epigenetic phenomena, both at the level of single genes and across larger chromosomal regions. Important progress has been made recently in understanding these silencing mechanisms. In addition, new insights have been gained into how this silencing has been co-opted to serve essential functions in 'host' cells, highlighting the importance of TEs in the epigenetic regulation of the genome.
1,823 citations
Wellcome Trust Sanger Institute1, J. Craig Venter Institute2, George Washington University3, 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.
1,631 citations
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
1,554 citations
TL;DR: Owing to their limited expression in gonads and their sequence diversity, piRNAs have been the most mysterious class of small non-coding RNAs regulating RNA silencing, but much progress is being made into the understanding of their biogenesis and molecular functions, including the specific subcellular compartmentalization of the piRNA pathway in granular cytoplasmic bodies.
Abstract: PIWI-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs that form the piRNA-induced silencing complex (piRISC) in the germ line of many animal species. The piRISC protects the integrity of the genome from invasion by 'genomic parasites' — transposable elements — by silencing them. Owing to their limited expression in gonads and their sequence diversity, piRNAs have been the most mysterious class of small non-coding RNAs regulating RNA silencing. Now, much progress is being made into our understanding of their biogenesis and molecular functions, including the specific subcellular compartmentalization of the piRNA pathway in granular cytoplasmic bodies.
1,163 citations
TL;DR: A decade after the beginning of the genomic era, the question of how genomics can describe a bacterial species has not been fully addressed and the pan-genome, which is composed of a "core genome" containing genes present in all strains, and a "dispensable genome", might be orders of magnitude larger than any single genome.
1,099 citations
References
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
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TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
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6,643 citations
French Institute of Health and Medical Research1, Hospital Research Foundation2, University of Freiburg3, Medical Research Council4, Utrecht University5, Harvard University6, Pasteur Institute7, Babraham Institute8, University of Paris9, Curie Institute10, National Institutes of Health11, University of Sydney12, Ludwig Maximilian University of Munich13, LSU Health Sciences Center New Orleans14
TL;DR: Retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
Abstract: We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
3,514 citations
TL;DR: The cloning of a human gene, hEST2, that shares significant sequence similarity with the telomerase catalytic subunit genes of lower eukaryotes is reported, suggesting that the induction of hEST 2 mRNA expression is required for the telomersase activation that occurs during cellular immortalization and tumor progression.
1,907 citations
TL;DR: Global analysis of cellular transcription indicated that active genes were preferential integration targets, particularly genes that were activated in cells after infection by HIV-1, and this data suggests how selective targeting promotes aggressive HIV replication.
1,808 citations