Characterization of a Plasmodium falciparum mutant that has deleted the majority of the gametocyte-specific Pf11-1 locus

Scherf, Artur; Petersen, Carolyn; Carter, Richard; Alano, Pietro; Nelson, Rick; Aikawa, Masamichi; Mattei, Denise; Silva, Luiz Pereira da; Leech, James H.

doi:10.1590/s0074-02761992000700012

Cited by 7 publications

(7 citation statements)

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“…Genomic regions that show a high propensity for segmental duplications also have been suggested in isolates [20] and laboratory lines [22] of P. falciparum . Additionally, previous work has also demonstrated extensive occurrence of deletions particularly in the subtelomeric sequences [44,46,48,84,85], indicating that the subtelomeric regions may be highly unstable and represent fragile sites [85,86]. It has been postulated that specific sequence features may underlie the fragility of the subtelomeric regions [85].…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with the expectation from MS linkage analysis, five of the CNV regions overlapped with the skewed allele distributed regions in the MS map, emphasizing the role of CNVs in parasite selection. The skewed regions overlap with genes associated with parasite pathogenicity [87], gametogenesis [44,46] and drug resistance [19]. Regions of skewed inheritance have been observed not only in the HB3 × Dd2 genetic cross [42,65], but also in other independent genetic crosses [42,88,89].…”

Section: Discussionmentioning

confidence: 99%

“…Chromosome size polymorphisms have been identified in various geographical isolates, in vitro drug selections and controlled genetic crosses by pulse field gel electrophoresis (PFGE) [38-41]. Duplications and inter-chromosomal transpositions of chromosome segments are thought to contribute to novel phenotypes [42-46]; chromosomal anomalies, e.g. the amplification of the pfmdr1 (PFE1150w) locus on chromosome (Chr) 5 [47], and the deletion of the KAHRP (PFB0100c) locus on Chr 2 [48] have been studied widely for their key roles in drug resistance and cytoadherence, respectively.…”

Section: Introductionmentioning

confidence: 99%

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The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross

et al. 2011

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BackgroundCopy number is a major source of genome variation with important evolutionary implications. Consequently, it is essential to determine copy number variant (CNV) behavior, distributions and frequencies across genomes to understand their origins in both evolutionary and generational time frames. We use comparative genomic hybridization (CGH) microarray and the resolution provided by a segregating population of cloned progeny lines of the malaria parasite, Plasmodium falciparum, to identify and analyze the inheritance of 170 genome-wide CNVs.ResultsWe describe CNVs in progeny clones derived from both Mendelian (i.e. inherited) and non-Mendelian mechanisms. Forty-five CNVs were present in the parent lines and segregated in the progeny population. Furthermore, extensive variation that did not conform to strict Mendelian inheritance patterns was observed. 124 CNVs were called in one or more progeny but in neither parent: we observed CNVs in more than one progeny clone that were not identified in either parent, located more frequently in the telomeric-subtelomeric regions of chromosomes and singleton de novo CNVs distributed evenly throughout the genome. Linkage analysis of CNVs revealed dynamic copy number fluctuations and suggested mechanisms that could have generated them. Five of 12 previously identified expression quantitative trait loci (eQTL) hotspots coincide with CNVs, demonstrating the potential for broad influence of CNV on the transcriptional program and phenotypic variation.ConclusionsCNVs are a significant source of segregating and de novo genome variation involving hundreds of genes. Examination of progeny genome segments provides a framework to assess the extent and possible origins of CNVs. This segregating genetic system reveals the breadth, distribution and dynamics of CNVs in a surprisingly plastic parasite genome, providing a new perspective on the sources of diversity in parasite populations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross

et al. 2011

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“…Forty orthologous pairs of sequences were chosen, fulfilling the following criteria; no known or hypothesised role in drug resistance or host interaction, syntenic relationship between P. falciparum and P. chabaudi and > 75% coverage in the P. reichenowi ortholog [18] (used for measurement of divergence within hominid malaria parasites). Since sexual-stage genes are released from purifying selection in asexual culture (experienced by several of the isolates under study) [43] genes with no evidence of asexual expression in transcriptomic surveys [44,45] were also excluded. In order to reflect the types of genes which are implicated in drug resistance, as well as to obtain a range of conservation levels across this reference set, the reference genes consisted of ATPases (8), secondarily active transporters (12), glycolytic enzymes (10) and enzymes involved in DNA and RNA processing (10)(Table 1).…”

Section: Methodsmentioning

confidence: 99%

Protein-based signatures of functional evolution in Plasmodium falciparum

et al. 2011

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BackgroundIt has been known for over a decade that Plasmodium falciparum proteins are enriched in non-globular domains of unknown function. The potential for these regions of protein sequence to undergo high levels of genetic drift provides a fundamental challenge to attempts to identify the molecular basis of adaptive change in malaria parasites.ResultsEvolutionary comparisons were undertaken using a set of forty P. falciparum metabolic enzyme genes, both within the hominid malaria clade (P. reichenowi) and across the genus (P. chabaudi). All genes contained coding elements highly conserved across the genus, but there were also a large number of regions of weakly or non-aligning coding sequence. These displayed remarkable levels of non-synonymous fixed differences within the hominid malaria clade indicating near complete release from purifying selection (dN/dS ratio at residues non-aligning across genus: 0.64, dN/dS ratio at residues identical across genus: 0.03). Regions of low conservation also possessed high levels of hydrophilicity, a marker of non-globularity. The propensity for such regions to act as potent sources of non-synonymous genetic drift within extant P. falciparum isolates was confirmed at chromosomal regions containing genes known to mediate drug resistance in field isolates, where 150 of 153 amino acid variants were located in poorly conserved regions. In contrast, all 22 amino acid variants associated with drug resistance were restricted to highly conserved regions. Additional mutations associated with laboratory-selected drug resistance, such as those in PfATPase4 selected by spiroindolone, were similarly restricted while mutations in another calcium ATPase (PfSERCA, a gene proposed to mediate artemisinin resistance) that reach significant frequencies in field isolates were located exclusively in poorly conserved regions consistent with genetic drift.ConclusionCoding sequences of malaria parasites contain prospectively definable domains subject to neutral or nearly neutral evolution on a scale that appears unrivalled in biology. This distinct evolutionary landscape has potential to confound analytical methods developed for other genera. Against this tide of genetic drift, polymorphisms mediating functional change stand out to such an extent that evolutionary context provides a useful signal for identifying the molecular basis of drug resistance in malaria parasites, a finding that is of relevance to both genome-wide and candidate gene studies in this genus.

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“…At the cellular level there is de novo synthesis of the proteins which are expressed on the surface of macrogamete . It was recently identified a gametocyte specific protein of P. falciparum called Pf11-1 and there is some evidence that this protein might be involved in the emergence of gametes from the infected erythrocyte (Scherf et al 1992(Scherf et al , 1993.…”

Section: Gametogenesismentioning

confidence: 99%