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Title: Comparative structural genomics and phylogenomics of African trypanosomes
Author: Abbas, Ali Hadi
ISNI:       0000 0004 7428 7358
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2018
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The pathogens responsible of the majority of African Animal trypanosomiasis (AAT) are Trypanosoma brucei, T. congolense and T. vivax. These three trypanosomes have very different biology both in the mammalian host and the insect vector. These differences are encoded in their genomes and whole genome sequence comparison of high quality genomic data should allow such comparisons to be performed. Whilst the T.b. brucei strain TREU927 genome assembly is currently aviable as a good quality draft, the current versions of T. congolense and T. vivax are highly fragmented and include large gaps that interrupt genes and physical integrity of genome assembly. Therefore, there is a need to produce high quality de novo genome assemblies of both T. congolense strain IL3000 and T. vivax IL1392. The most appropriate technology for this currently are the third generation sequencing such as PacBio SMRT long reads sequencing. This technology's long reads permit assembly to a high standard with good contig lengths, and more completed gene models. Comparative genomic analysis carried out on T. brucei large chromosomes and the new PacBio de novo assemblies in this thesis T. congolense and T. vivax uncovered putative large structural chromosomal rearrangements between the African trypanosomes. The most extensive examples were noticed between T. vivax and T. brucei, which might reflect the early divergence of former to the most recent divergence of the latter in the phylogenetic tree of African trypanosomes. Remarkably, analysis of T. congolense genome assembly facilitated the full description of (minichromosomes) devoted to harbouring genes utilized mainly in mammalian host immune evasion mechanism. Subsequently, a new gene family consisting of about 30 genes/pseudogenes encode for putative surface proteins (ESAG3- like proteins) was assigned to this trypanosome most likely only found on these chromosomes. The phylogenomic analysis of free living and parasitic kinetoplastids uncovered possible core kinetoplastids, parasitic and African trypanosome specific gene sets. Likewise, the genomic repertoire of some stage specific proteins like Haptoglobin-Hemoglobin receptor, PAG, BARP, ESAG6/7- transferrin like proteins were also present among analysed African trypanosomes. In conclusion, this project has provided genomes that give access to new genomic regions especially, the minichromosomes in two strains T. congolense and other interesting sequences of repeated nature in MBCs like centromeres, moreover, it shows unprecedented chromosomal rearrangements across the three African trypanosomes. Finally, phylogenomic analysis revealed for the first time the genomic repertoire of Haptoglobin- Hemoglobin receptor in the African trypanosomes.
Supervisor: Darby, Alistair Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral