Browsing by Author "Doak, T.G."
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Item Consequences of whole genome duplication in Paramecium sps.(2014-01) McGrath, C.L.; Gout, J.F.; Johri, P.; Doak, T.G.; Lynch, M.Item Consequences of whole genome duplication in Paramecium sps.(2013-07) McGrath, C.L.; Gout, J.F.; Johri, P.; Doak, T.G.; Lynch, M.Item Consequences of whole genome duplication in Paramecium sps.(2013-05) McGrath, C.L.; Gout, J.F.; Johri, P.; Doak, T.G.; Lynch, M.Item Diverse CRISPRs evolving in human microbiomes(Public Library of Science, 2012) Rho, M.; Wu, Y.-W.; Tang, H.; Doak, T.G.; Ye, Y.CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci, together with cas (CRISPR-associated) genes, form the CRISPR/Cas adaptive immune system, a primary defense strategy that eubacteria and archaea mobilize against foreign nucleic acids, including phages and conjugative plasmids. Short spacer sequences separated by the repeats are derived from foreign DNA and direct interference to future infections. The availability of hundreds of shotgun metagenomic datasets from the Human Microbiome Project (HMP) enables us to explore the distribution and diversity of known CRISPRs in human-associated microbial communities and to discover new CRISPRs. We propose a targeted assembly strategy to reconstruct CRISPR arrays, which whole-metagenome assemblies fail to identify. For each known CRISPR type (identified from reference genomes), we use its direct repeat consensus sequence to recruit reads from each HMP dataset and then assemble the recruited reads into CRISPR loci; the unique spacer sequences can then be extracted for analysis. We also identified novel CRISPRs or new CRISPR variants in contigs from whole-metagenome assemblies and used targeted assembly to more comprehensively identify these CRISPRs across samples. We observed that the distributions of CRISPRs (including 64 known and 86 novel ones) are largely body-site specific. We provide detailed analysis of several CRISPR loci, including novel CRISPRs. For example, known streptococcal CRISPRs were identified in most oral microbiomes, totaling ~8,000 unique spacers: samples resampled from the same individual and oral site shared the most spacers; different oral sites from the same individual shared significantly fewer, while different individuals had almost no common spacers, indicating the impact of subtle niche differences on the evolution of CRISPR defenses. We further demonstrate potential applications of CRISPRs to the tracing of rare species and the virus exposure of individuals. This work indicates the importance of effective identification and characterization of CRISPR loci to the study of the dynamic ecology of microbiomes.Item NCGAS: Providing National Cyberinfrastructure to Biologists, with a Focus on Genomics(2017-04-21) Doak, T.G.; Blood, Phil; Ganote, Carrie; Sanders, SheriItem Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes(American Society for Microbiology, 2012) Wu, Y.-W.; Rho, M.; Doak, T.G.; Ye, Y.The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic data sets, allowing studies of the many functional elements in human-associated microbial communities. Here, we survey the distribution of oral spirochetes implicated in dental diseases in normal human individuals, using recombination sites associated with the chromosomal integron in Treponema genomes, taking advantage of the multiple copies of the integron recombination sites (repeats) in the genomes, and using a targeted assembly approach thatwe have developed. We find that integron-containing Treponema species are present in 80%of the normal human subjects included in the HMP. Further, we are able to de novo assemble the integron gene cassettes using our constrained assembly approach, which employs a unique application of the de Bruijn graph assembly information;most of these cassette genes were not assembled in whole-metagenome assemblies and could not be identified by mapping sequencing reads onto the known reference Treponema genomes due to the dynamic nature of integron gene cassettes. Our studysignificantly enriches the gene pool known to be carried by Treponema chromosomal integrons, totaling 826 (598 97% nonredundant) enes. We characterize the functions of these gene cassettes: many of these genes have unknown functions. The integron gene cassette arrays found in the human microbiome are extraordinarily dynamic, with different microbial communities sharing only a small number of common genes.Item Whole-genome duplication, the Paramecium aurelia radiation, and the evolution of gene expression.(2014-04-12) Doak, T.G.; Gout, J.F.; Bright, L.; Johri, P.; Sung, W.; Lynch, M.; McGrath, C.L.