Understanding the genomic relationship between nuclear DNA replication and genome plasticity in kinetoplastid genomes

QR180 Immunology

Campbell, Samantha Jane ; Dickens, Nicholas J.

University:University of Glasgow

Department:Institute of Infection Immunity and Inflammation

关键词: kinetoplastid, Leishmania, Trypanosoma, DNA replication, plasticity, genomics.;   

Others  :  http://theses.gla.ac.uk/74256/1/2019CampbellSJPhD.pdf

来源: University of Glasgow

【 摘 要 】

DNA replication is an essential process in all eukaryotes initiated from sites termed origins of replication. Recent studies in the kinetoplastid species Leishmania and Trypanosoma brucei have revealed striking differences in the process of DNA replication between the largely syntenic genomes. T. brucei replication origins are generally consistent with previous eukaryotic models while Leishmania chromosomes appears to contain a single major origin, as is observed in bacteria, although how the parasites can complete replication in this manner remains unknown. Sites of DNA replication co-localise to strand switch regions where transcription initiation and termination also occur. However, not every strand switch region contains an origin of replication and differences between those containing an origin and those without have not been identified. The use of a variety of computational approaches, including machine learning, allow the investigation of origins of replication in both Leishmania and Trypanosoma brucei at the DNA sequence level and within the structure of the surrounding genomic context and further characterization of the different classes of strand switch region.A significant feature of the Leishmania genome is its ability to adapt in response to environmental pressures through copy number variation of genes and chromosomes and the formation of episomes, allowing the parasites to evade the host immune system and rapidly develop drug resistance through modulation of gene expression. Analysis of the sequence and structure of the Leishmania mexicana genome in serial passage conditions provides insight into the mechanisms underlying genome plasticity and presents a novel hypothesis explaining the potential relationship with DNA replication.