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Whole genome experimental maps of DNA G-quadruplexes in multiple species.

ABSTRACT: Genomic maps of DNA G-quadruplexes (G4s) can help elucidate the roles that these secondary structures play in various organisms. Herein, we employ an improved version of a G-quadruplex sequencing method (G4-seq) to generate whole genome G4 maps for 12 species that include widely studied model organisms and also pathogens of clinical relevance. We identify G4 structures that form under physiological K+ conditions and also G4s that are stabilized by the G4-targeting small molecule pyridostatin (PDS). We discuss the various structural features of the experimentally observed G-quadruplexes (OQs), highlighting differences in their prevalence and enrichment across species. Our study describes diversity in sequence composition and genomic location for the OQs in the different species and reveals that the enrichment of OQs in gene promoters is particular to mammals such as mouse and human, among the species studied. The multi-species maps have been made publicly available as a resource to the research community. The maps can serve as blueprints for biological experiments in those model organisms, where G4 structures may play a role.

SUBMITTER: Marsico G

PROVIDER: S-EPMC6486626 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Whole genome experimental maps of DNA G-quadruplexes in multiple species.

Marsico Giovanni G Chambers Vicki S VS Sahakyan Aleksandr B AB McCauley Patrick P Boutell Jonathan M JM Antonio Marco Di MD Balasubramanian Shankar S

Nucleic acids research 20190501 8

Genomic maps of DNA G-quadruplexes (G4s) can help elucidate the roles that these secondary structures play in various organisms. Herein, we employ an improved version of a G-quadruplex sequencing method (G4-seq) to generate whole genome G4 maps for 12 species that include widely studied model organisms and also pathogens of clinical relevance. We identify G4 structures that form under physiological K+ conditions and also G4s that are stabilized by the G4-targeting small molecule pyridostatin (PD ...[more]

PMID: 30892612

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Project description:BackgroundReconstructing the evolutionary history of organisms using traditional phylogenetic methods may suffer from inaccurate sequence alignment. An alternative approach, particularly effective when whole genome sequences are available, is to employ methods that don't use explicit sequence alignments. We extend a novel phylogenetic method based on Singular Value Decomposition (SVD) to reconstruct the phylogeny of 12 sequenced Drosophila species. SVD analysis provides accurate comparisons for a high fraction of sequences within whole genomes without the prior identification of orthologs or homologous sites. With this method all protein sequences are converted to peptide frequency vectors within a matrix that is decomposed to provide simplified vector representations for each protein of the genome in a reduced dimensional space. These vectors are summed together to provide a vector representation for each species, and the angle between these vectors provides distance measures that are used to construct species trees.ResultsAn unfiltered whole genome analysis (193,622 predicted proteins) strongly supports the currently accepted phylogeny for 12 Drosophila species at higher dimensions except for the generally accepted but difficult to discern sister relationship between D. erecta and D. yakuba. Also, in accordance with previous studies, many sequences appear to support alternative phylogenies. In this case, we observed grouping of D. erecta with D. sechellia when approximately 55% to 95% of the proteins were removed using a filter based on projection values or by reducing resolution by using fewer dimensions. Similar results were obtained when just the melanogaster subgroup was analyzed.ConclusionsThese results indicate that using our novel phylogenetic method, it is possible to consult and interpret all predicted protein sequences within multiple whole genomes to produce accurate phylogenetic estimations of relatedness between Drosophila species. Furthermore, protein filtering can be effectively applied to reduce incongruence in the dataset as well as to generate alternative phylogenies.

Dataset Information

Whole genome experimental maps of DNA G-quadruplexes in multiple species.

Publications

Whole genome experimental maps of DNA G-quadruplexes in multiple species.

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