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Culture adaptation of malaria parasites selects for convergent loss-of-function mutants
- Source :
- Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Cultured human pathogens may differ significantly from source populations. To investigate the genetic basis of laboratory adaptation in malaria parasites, clinical Plasmodium falciparum isolates were sampled from patients and cultured in vitro for up to three months. Genome sequence analysis was performed on multiple culture time point samples from six monoclonal isolates, and single nucleotide polymorphism (SNP) variants emerging over time were detected. Out of a total of five positively selected SNPs, four represented nonsense mutations resulting in stop codons, three of these in a single ApiAP2 transcription factor gene, and one in SRPK1. To survey further for nonsense mutants associated with culture, genome sequences of eleven long-term laboratory-adapted parasite strains were examined, revealing four independently acquired nonsense mutations in two other ApiAP2 genes, and five in Epac. No mutants of these genes exist in a large database of parasite sequences from uncultured clinical samples. This implicates putative master regulator genes in which multiple independent stop codon mutations have convergently led to culture adaptation, affecting most laboratory lines of P. falciparum. Understanding the adaptive processes should guide development of experimental models, which could include targeted gene disruption to adapt fastidious malaria parasite species to culture.
- Subjects :
- 0301 basic medicine
Sequence analysis
Plasmodium falciparum
030106 microbiology
Mutant
Nonsense mutation
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
Genome
Article
03 medical and health sciences
Loss of Function Mutation
Animals
Humans
Parasites
Malaria, Falciparum
Gene
Alleles
Genetics
Multidisciplinary
Sequence Analysis, DNA
biology.organism_classification
Adaptation, Physiological
Stop codon
3. Good health
030104 developmental biology
Codon, Nonsense
Subjects
Details
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....827f887da05886582c3236f6939c9c3a