Analysis of the genome of the filarial nematode Brugia malayi

• Main Author: Guiliano, David Bernardo
• Published: University of Edinburgh 2002
• Subjects: 591.35
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651862

The thesis is about developing the ‘genomes’ approach to the study of the evolution of nematode genes and genomes. CDNA clones were sequences on a large scale to produce EST datasets from a human lymphatic and cutaneous filarial worm. These were also productively compared with EST and whole genome sequencing efforts in other nematodes, notably <i>C. elegans. </i>Many new nematode gene families were identified for further analysis and interestingly, the two filarial datasets do not show similar patterns of gene family expression in any stage of the life cycle except the infective L3 larvae. The biology of host parasite interaction was reviewed fairly succinctly (some spelling and grammatical errors were overlooked in this otherwise satisfactory Introduction). The methodology and computing strategies used to generate and handle the EST sequence analysis was described and the novel methods developed detailed. This is of course the essential foundation of the genomic approach and is worthy of publication, perhaps via web-based distribution or journal. A specific aspect of host-parasite interaction biology is addressed in the candidates studies of the observations that filarial parasites encode a homologue of the vertebrate cytokine known as the Macrophage Inhibitory Factor. Two MIF genes were found in both <i>B. malayi </i>and <i>O. volvulus. </i>However, the non-parasitic nematode <i>C. elegans </i>also has 4 MIF genes, as do plant parasitic nematodes. This thesis also discovered that MIF genes seem to exist in several parasitic protozoa. The potential, but not proven role of MIFs as parasite immuno-regulators of the host immune response was therefore extensively discussed. To examine the “mode and tempo” of genome evolution studies of the relative order of genes in the two species was analysed and extensively discussed. A similar exercise was carried out on analysing operonic structures in <i>C. elegans, B. malayi, S. ratti</i> and <i>P. pacificus. </i>How common operons actually are was not resolved.