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• W70797318 abstract "P. falciparum and P. vivax are two human malaria pathogens. Although these parasites share the same hosts, they are evolutionary distant species, differing in genome composition and organisation, parasite life cycle and clinical manifestations. Genome comparison of these two species is fundamental to increase our understanding of common biological processes, as well as unique properties of each pathogen, which is necessary for the development of species specific or pan-species diagnostic tools, antimalarial drugs and vaccines. To investigate the level of conservation between P. falciparum and P. vivax a continuous region of a P. vivax chromosome cloned in the YAC 1H14 was sequenced. Within this 199,866 base pair portion of P. vivax chromosome, a conserved linkage group was identified consisting of at least 41 genes homologous to P. falciparum genes located on chromosome 3. Within this conserved linkage group, the gene order and structure are identical to that of P. falciparum chromosome 3. Furthermore, this conserved linkage group may contain as many as 190 genes. Although there are large regions of similarity between the P. falciparum and P. vivax chromosomes, there were two regions where no homology with P. falciparum chromosome 3 was observed. The first region contained the P. falciparum cytoadherence-linked asexual genes clag 3.2, clag 3.1 and a var C pseudogene for which no homologues could be found on the section of P. vivax chromosome analysed. Secondly, there was no homology observed between the subtelomeric regions of the P. vivax chromosome and P. falciparum chromosome 3. In addition, the subtelomeric region of the analysed P. vivax chromosome is 90 kb longer than that of P. falciparum chromosome 3. The overall size difference of at least 900 kb between the entire homologous P. vivax chromosome and P. falciparum chromosome 3 is presumably due to a translocation from another chromosome. The region of the P. vivax chromosome homologous to P. falciparum has a much higher DNA GC-content compared to that of P. falciparum. There is a preference for amino acids using GC-rich codons in the deduced proteins of P. vivax compared to P. falciparum orthologues. Nevertheless, there is a high degree of functional conservation between the orthologous proteins identified within this locus. The degree of sequence similarity between the orthologous proteins varied from 23% to 97%. Thus, both highly conserved and diverged proteins could be readily identified by the comparative analysis. This approach is of great value for initial functional characterisation of the genes in both species. Pairwise alignments were used to search for phylogenetic footprints within noncoding sequences. In contrast to the coding sequences, the intergenic regions and introns of P. vivax have diverged substantially from those of P. falciparum. The number of footprints found within the non-coding sequences of P. vivax and P. falciparum is considerably less than that between P. falciparum and the rodent parasite P. yoelii. Only 4% of nucleotides appear to be conserved between the P. vivax and P. falciparum intergenic sequences. This is much lower than the fraction of conserved nucleotides in the coding sequences and is indicative of a different type of selection pressure acting on non-coding sequences. The effect of sequence divergence on the cross-species functionality of promoter regions was tested. The ability of several homologous P. vivax, P. falciparum and P. yoelii promoter regions to drive expression of a reporter gene was compared. The expression of the reporter gene under control of the homologous P. falciparum and P. yoelii promoter regions was detected at comparable levels, whereas expression under control of the P. vivax promoter regions was not detectable. The decrease in activity of the P. vivax promoters appears to be consistent with the lack of conservation between the non-coding sequences of P. vivax and P. falciparum. In conclusion, this thesis combines molecular biology techniques and bioinformatic analyses to characterise a P. vivax chromosomal segment. This study revealed for the first time a high degree of conservation between the genomes of the two evolutionary distant parasites P. falciparum and P. vivax, and demonstrated the power of comparative genomics for studying Plasmodium species. This work also contributed to the P. vivax genome sequencing initiative leading to the whole genome sequencing of P. vivax." @default.
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• W70797318 date "2006-01-01" @default.
• W70797318 modified "2023-09-27" @default.
• W70797318 title "Comparison of a chromosomal segment of P. vivax with that of P. falciparum" @default.
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