Long- and short-term selective forces on malaria parasite genomes
Name:
Article-PLoS_Genet-Long-_and_-2010.pdf
Size:
739.2Kb
Format:
PDF
Description:
Article - Full Text
Name:
Supplement_1_-_PLoS_Genet-Long-_and_-2010.pgen.1001099.s001.pdf
Size:
120.5Kb
Format:
PDF
Description:
Supplemental File 1
Name:
Supplement_2_-_PLoS_Genet-Long-_and_-2010.pgen.1001099.s002.pdf
Size:
114.0Kb
Format:
PDF
Description:
Supplemental File 2
Type
ArticleAuthors
Nygaard, SanneBraunstein, Alexander
Malsen, Gareth
Van Dongen, Stijn
Gardner, Paul P.
Krogh, Anders
Otto, Thomas D.
Pain, Arnab
Berriman, Matthew
McAuliffe, Jon
Dermitzakis, Emmanouil T.
Jeffares, Daniel C.
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Pathogen Genomics Laboratory
Date
2010-09-09Permanent link to this record
http://hdl.handle.net/10754/325277Metadata
Show full item recordAbstract
Plasmodium parasites, the causal agents of malaria, result in more than 1 million deaths annually. Plasmodium are unicellular eukaryotes with small ~23 Mb genomes encoding ~5200 protein-coding genes. The protein-coding genes comprise about half of these genomes. Although evolutionary processes have a significant impact on malaria control, the selective pressures within Plasmodium genomes are poorly understood, particularly in the non-protein-coding portion of the genome. We use evolutionary methods to describe selective processes in both the coding and non-coding regions of these genomes. Based on genome alignments of seven Plasmodium species, we show that protein-coding, intergenic and intronic regions are all subject to purifying selection and we identify 670 conserved non-genic elements. We then use genome-wide polymorphism data from P. falciparum to describe short-term selective processes in this species and identify some candidate genes for balancing (diversifying) selection. Our analyses suggest that there are many functional elements in the non-genic regions of these genomes and that adaptive evolution has occurred more frequently in the protein-coding regions of the genome. © 2010 Nygaard et al.Citation
Nygaard S, Braunstein A, Malsen G, Van Dongen S, Gardner PP, et al. (2010) Long- and Short-Term Selective Forces on Malaria Parasite Genomes. PLoS Genet 6: e1001099. doi:10.1371/journal.pgen.1001099.Publisher
Public Library of Science (PLoS)Journal
PLoS GeneticsPubMed ID
20838588PubMed Central ID
PMC2936524Scopus Count
Related items
Showing items related by title, author, creator and subject.
-
Characterization and gene expression analysis of the cir multi-gene family of plasmodium chabaudi chabaudi (AS)(BMC Genomics, Springer Nature, 2012-03-29) [Article]Background: The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species. Despite comprising up to 5% of the genome, little is known about the functions of the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice, which may be due to antigenic variation. In this model, pir genes are called cirs and may be involved in this mechanism, allowing evasion of host immune responses. In order to fully understand the role(s) of CIR proteins during P. chabaudi infection, a detailed characterization of the cir gene family was required.Results: The cir repertoire was annotated and a detailed bioinformatic characterization of the encoded CIR proteins was performed. Two major sub-families were identified, which have been named A and B. Members of each sub-family displayed different amino acid motifs, and were thus predicted to have undergone functional divergence. In addition, the expression of the entire cir repertoire was analyzed via RNA sequencing and microarray. Up to 40% of the cir gene repertoire was expressed in the parasite population during infection, and dominant cir transcripts could be identified. In addition, some differences were observed in the pattern of expression between the cir subgroups at the peak of P. chabaudi infection. Finally, specific cir genes were expressed at different time points during asexual blood stages.Conclusions: In conclusion, the large number of cir genes and their expression throughout the intraerythrocytic cycle of development indicates that CIR proteins are likely to be important for parasite survival. In particular, the detection of dominant cir transcripts at the peak of P. chabaudi infection supports the idea that CIR proteins are expressed, and could perform important functions in the biology of this parasite. Further application of the methodologies described here may allow the elucidation of CIR sub-family A and B protein functions, including their contribution to antigenic variation and immune evasion. 2012 Lawton et al; licensee BioMed Central Ltd.
-
Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites(BMC Genomics, Springer Nature, 2010-09-16) [Article]Background: Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum.Results: A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (IlluminaSolexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme.Conclusions: This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations. 2010 Hunt et al; licensee BioMed Central Ltd.
-
A scalable pipeline for highly effective genetic modification of a malaria parasite(Nature Methods, Springer Nature, 2011-10-23) [Article]In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Red method of recombineering. We built a pipeline for generating P. berghei genetic modification vectors at genome scale in serial liquid cultures on 96-well plates. Vectors have long homology arms, which increase recombination frequency up to tenfold over conventional designs. The feasibility of efficient genetic modification at scale will stimulate collaborative, genome-wide knockout and tagging programs for P. berghei. © 2011 Nature America, Inc. All rights reserved.
