Dokument: Determinants of bacterial fitness and their impact on prokaryotic genome evolution

Titel:	Determinants of bacterial fitness and their impact on prokaryotic genome evolution
Weiterer Titel:	Determinanten der bakteriellen Fitness und ihrer Auswirkung auf die prokaryotische Genomentwicklung
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=51720
URN (NBN):	urn:nbn:de:hbz:061-20191205-151709-8
Kollektion:	Dissertationen
Sprache:	Englisch
Dokumententyp:	Wissenschaftliche Abschlussarbeiten » Dissertation
Medientyp:	Text
Autor:	Gao, Na [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 7,97 MB in einer Datei [ZIP-Datei erzeugen] Dateien vom 05.12.2019 / geändert 05.12.2019
Beitragende:	Prof. Dr. Lercher, Martin [Gutachter] Prof. Dr. Martin, William [Gutachter] Prof. Dr. Chen, Wei-Hua [Gutachter]
Dewey Dezimal-Klassifikation:	000 Informatik, Informationswissenschaft, allgemeine Werke » 004 Datenverarbeitung; Informatik
Beschreibung:	Prokaryotes thrive in all known habitats on earth. They have important industrial values and a significant impact on human health. In this thesis, I interrogate recently published (meta-)genomic sequences generated by high-throughput sequencing techniques to identify key factors that contribute to the fitness of prokaryotes and the impacts on their genomes. We first explored intrinsic factors. A previous study of our group identified that efficient resource usage shapes nucleotide usage in coding regions of prokaryotic genomes. In this study, we further revealed that efficient resource usage could also drive genes to be preferably located on the leading strand, an observation known as strand-biased gene distribution (SGD). The leading strand is synthesized in the same direction as the movement of the replication fork, while the lagging strand is synthesized in the opposite direction. The transcription and replication machineries collide head-to-head on the lagging strand, leading to longer exposure time of single-stranded DNA to chemical modifications. Lagging strand genes thus accumulate more deleterious mutations. Mutational biases introduced energetically cheaper nucleotides on the lagging strand, resulting in more expensive protein products, which consequently drove genes to the leading strand. We tested our mutagenesis/energy efficiency model in 1,552 prokaryotic genomes and found that mutational biases in non-transcribed regions can explain ~71% of the variation in SGDs; consistently, the difference between averaged amino acid costs of proteins encoded by genes on the two strands explained ~50% of the variance in SGDs. We next explored external factors such as bacteriophages. Phages invade microbes, accomplish host lysis, and are of vital importance in shaping the community structure of environmental microbiota. Phage-mediated horizontal gene transfer is known to have a significant impact on the formation, evolution,and host range transition of virulence factors of pathogenic bacteria. We first identified 26,572 interactions between 18,608 viral clusters (complete and fragmented phage genomes) and 9,245 prokaryotes (i.e., bacteria and archaea). Based on these interactions, we calculated the host range for each of the phage clusters, and accordingly grouped them into subgroups such as species-, genus-, and family-specific phage clusters. We also calculated the size and GC-content of bacteria for the gut metagenome, which contains a variety of bacteriophages,plasmids, and CRISPRs. We found that both phages and plasmids contribute significantly to genome expansion, i.e., genomes with phages and/or plasmids are significantly larger than those without; the genome sizes were increased with increasing numbers of associated phages/plasmids. Conversely, we found that CRISPR systems have a negative impact on genome size, i.e., genomes with CRISPRs are significantly smaller in size than those without. These results confirmed that on an evolutionary timescale, phages and plasmids facilitated genome expansions while CRISPR impaired such processes in prokaryotes. Furthermore, our results also revealed a striking yet expected preference of CRISPR systems against phages over plasmids, consistent with the typical consequences of phage and plasmid infection to the hosts and the roles of CRISPR as a defence system. Finally, we constructed an MVP database (microbe-phage interaction database) using the results of our microbe-phage interaction analysis. Phages can be used as antibiotic agents for pathogenic prokaryotes and/or a tool to specifically “knockdown” target prokaryotes without affecting others. Therefore,such a resource will be useful in (meta-)genomic studies and of potential clinical importance.
Lizenz:	Urheberrechtsschutz
Fachbereich / Einrichtung:	Mathematisch- Naturwissenschaftliche Fakultät
Dokument erstellt am:	05.12.2019
Dateien geändert am:	05.12.2019
Promotionsantrag am:	05.12.2018
Datum der Promotion:	02.12.2019