劣化古人骨試料の包括的ミトコンドリアゲノム分析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 近藤 修, 東京大学講師 井原 泰雄, 東邦大学教授 黒﨑 久仁彦, 総合研究大学院大学講師 五條堀 淳, 首都大学東京教授 田村 若一郎, 東京大学教授 植田 信太郎University of Tokyo(東京大学

Comparative Genome Analysis Reveals Accumulation of Single-Nucleotide Repeats in Pathogenic Escherichia Lineages

Homopolymeric tracts (HPTs) can lead to phase variation and DNA replication slippage, driving adaptation to environmental changes and evolution of genes and genomes. However, there is limited information on HPTs in Escherichia; therefore, we conducted a comprehensive cross-strain search for HPTs in Escherichia genomes. We determined the HPT genomic distribution and identified a pattern of high-frequency HPT localization in pathogenic Escherichia lineages. Notably, HPTs localized near transcriptional regulatory genes. Additionally, excessive repeats accumulated in toxin-coding genes. Moreover, the genomic localization of some HPTs might be derived from exogenous DNA, such as that of bacteriophages. Altogether, our findings may prove useful for understanding the role of HPTs in Escherichia genomes

MitoSuite: a graphical tool for human mitochondrial genome profiling in massive parallel sequencing

Recent rapid advances in high-throughput, next-generation sequencing (NGS) technologies have promoted mitochondrial genome studies in the fields of human evolution, medical genetics, and forensic casework. However, scientists unfamiliar with computer programming often find it difficult to handle the massive volumes of data that are generated by NGS. To address this limitation, we developed MitoSuite, a user-friendly graphical tool for analysis of data from high-throughput sequencing of the human mitochondrial genome. MitoSuite generates a visual report on NGS data with simple mouse operations. Moreover, it analyzes high-coverage sequencing data but runs on a stand-alone computer, without the need for file upload. Therefore, MitoSuite offers outstanding usability for handling massive NGS data, and is ideal for evolutionary, clinical, and forensic studies on the human mitochondrial genome variations. It is freely available for download from the website https://mitosuite.com

Comparative Genome Analysis Reveals Accumulation of Single-Nucleotide Repeats in Pathogenic <i>Escherichia</i> Lineages

Homopolymeric tracts (HPTs) can lead to phase variation and DNA replication slippage, driving adaptation to environmental changes and evolution of genes and genomes. However, there is limited information on HPTs in Escherichia; therefore, we conducted a comprehensive cross-strain search for HPTs in Escherichia genomes. We determined the HPT genomic distribution and identified a pattern of high-frequency HPT localization in pathogenic Escherichia lineages. Notably, HPTs localized near transcriptional regulatory genes. Additionally, excessive repeats accumulated in toxin-coding genes. Moreover, the genomic localization of some HPTs might be derived from exogenous DNA, such as that of bacteriophages. Altogether, our findings may prove useful for understanding the role of HPTs in Escherichia genomes

Outlier Detection for Minor Compositional Variations in Taxonomic Abundance Data

To understand the activities of complex microbial communities in various natural environments and living organisms, we need to capture the compositional changes in their taxonomic abundance. Here, we propose a new computational framework to detect compositional changes in microorganisms, including minor bacteria. This framework is designed to statistically assess relative variations in taxonomic abundance. By using this approach, we detected compositional changes in the human gut microbiome that might be associated with short-term human dietary changes. Our approach can shed light on the compositional changes of minor microorganisms that are easily overlooked

Genome Sequence of Rhodococcus erythropolis Type Strain JCM 3201

Rhodococcus erythropolis JCM 3201 can express several recombinant proteins that are difficult to express in Escherichia coli. It is used as one of the hosts for protein expression and bioconversion. Here, we report the draft genome sequence of R. erythropolis JCM 3201

Evolutionary History of the Risk of SNPs for Diffuse-Type Gastric Cancer in the Japanese Population

A genome wide association study reported that the T allele of rs2294008 in a cancer-related gene, PSCA, is a risk allele for diffuse-type gastric cancer. This allele has the highest frequency (0.63) in Japanese in Tokyo (JPT) among 26 populations in the 1000 Genomes Project database. FST &asymp; 0.26 at this single nucleotide polymorphism is one of the highest between JPT and the genetically close Han Chinese in Beijing (CHB). To understand the evolutionary history of the alleles in PSCA, we addressed: (i) whether the C non-risk allele at rs2294008 is under positive selection, and (ii) why the mainland Japanese population has a higher T allele frequency than other populations. We found that haplotypes harboring the C allele are composed of two subhaplotypes. We detected that positive selection on both subhaplotypes has occurred in the East Asian lineage. However, the selection on one of the subhaplotypes in JPT seems to have been relaxed or ceased after divergence from the continental population; this may have caused the elevation of T allele frequency. Based on simulations under the dual structure model (a specific demography for the Japanese) and phylogenetic analysis with ancient DNA, the T allele at rs2294008 might have had high frequency in the Jomon people (one of the ancestral populations of the modern Japanese); this may explain the high T allele frequency in the extant Japanese