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dc.contributor.authorGiordano, Jotien_US
dc.contributor.authorGe, Yongchaoen_US
dc.contributor.authorGelfand, Yevgeniyen_US
dc.contributor.authorAbrusán, Györgyen_US
dc.contributor.authorBenson, Garyen_US
dc.contributor.authorWarburton, Peter Een_US
dc.date.accessioned2012-01-11T16:54:59Z
dc.date.available2012-01-11T16:54:59Z
dc.date.issued2007-7-13en_US
dc.identifier.citationGiordano, Joti, Yongchao Ge, Yevgeniy Gelfand, György Abrusán, Gary Benson, Peter E Warburton. "Evolutionary History of Mammalian Transposons Determined by Genome-Wide Defragmentation" PLoS Computational Biology 3(7): e137. (2007)en_US
dc.identifier.issn1553-7358en_US
dc.identifier.urihttp://hdl.handle.net/2144/3130
dc.description.abstractThe constant bombardment of mammalian genomes by transposable elements (TEs) has resulted in TEs comprising at least 45% of the human genome. Because of their great age and abundance, TEs are important in comparative phylogenomics. However, estimates of TE age were previously based on divergence from derived consensus sequences or phylogenetic analysis, which can be unreliable, especially for older more diverged elements. Therefore, a novel genome-wide analysis of TE organization and fragmentation was performed to estimate TE age independently of sequence composition and divergence or the assumption of a constant molecular clock. Analysis of TEs in the human genome revealed ∼600,000 examples where TEs have transposed into and fragmented other TEs, covering >40% of all TEs or ∼542 Mbp of genomic sequence. The relative age of these TEs over evolutionary time is implicit in their organization, because newer TEs have necessarily transposed into older TEs that were already present. A matrix of the number of times that each TE has transposed into every other TE was constructed, and a novel objective function was developed that derived the chronological order and relative ages of human TEs spanning >100 million years. This method has been used to infer the relative ages across all four major TE classes, including the oldest, most diverged elements. Analysis of DNA transposons over the history of the human genome has revealed the early activity of some MER2 transposons, and the relatively recent activity of MER1 transposons during primate lineages. The TEs from six additional mammalian genomes were defragmented and analyzed. Pairwise comparison of the independent chronological orders of TEs in these mammalian genomes revealed species phylogeny, the fact that transposons shared between genomes are older than species-specific transposons, and a subset of TEs that were potentially active during periods of speciation. Author Summary. Transposable elements (TEs) are interspersed repetitive DNA families that are capable of copying themselves from place to place; they have literally infested our genome over evolutionary time, and now comprise as much as 45% of our total DNA. Because of their great age and abundance, TEs are important in evolutionary genomics. However, estimates of their age based on DNA sequence composition have been unreliable, especially for older more diverged elements. Therefore, a novel method to estimate the age of TEs was developed based on the fact that as TEs spread throughout the genome, they inserted into and fragmented older TEs that were already present. Therefore, the age of TEs can be revealed by how often they have been fragmented over evolutionary time. We performed a genome-wide defragmention of TEs, and developed a novel objective function to derive the chronological order of TEs spanning <100 million years. This method has been used to infer the relative ages of TEs from seven sequenced mammalian genomes across all four major TE classes, including the oldest, most diverged elements. This age estimate is independent of TE sequence composition or divergence and does not rely on the assumption of a constant molecular clock. This study provides a novel analysis of the evolutionary history of some of the most abundant and ancient repetitive DNA elements in mammalian genomes, which is important for understanding the dynamic forces that shape our genomes during evolution.en_US
dc.description.sponsorshipNational Institutes of Health (R01 GM07208)en_US
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.titleEvolutionary History of Mammalian Transposons Determined by Genome-Wide Defragmentationen_US
dc.typearticleen_US
dc.identifier.doi10.1371/journal.pcbi.0030137en_US
dc.identifier.pubmedid17630829en_US
dc.identifier.pmcid1914374en_US


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