Extreme mutation bias and high AT content in Plasmodium falciparum

For reasons that remain unknown, the Plasmodium falciparum genome has an exceptionally high AT content compared to other Plasmodium species and eukaryotes in general - nearly 80% in coding regions and approaching 90% in non-coding regions. Here, we examine how this phenomenon relates to genome-wide...

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Bibliographic Details
Published in:Nucleic acids research 2017-02, Vol.45 (4), p.1889-1901
Main Authors: Hamilton, William L, Claessens, Antoine, Otto, Thomas D, Kekre, Mihir, Fairhurst, Rick M, Rayner, Julian C, Kwiatkowski, Dominic
Format: Article
Language:English
Subjects:
Base Composition
Biochemistry, Molecular Biology
Gene Expression Regulation
Genetics
Genome, Protozoan
Genomics
INDEL Mutation
Life Sciences
Microbiology and Parasitology
Mutation
Mutation Rate
Parasitology
Phylogeny
Plasmodium falciparum - classification
Plasmodium falciparum - genetics
Polymorphism, Single Nucleotide
Populations and Evolution
Recombination, Genetic
Reproducibility of Results
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Summary:For reasons that remain unknown, the Plasmodium falciparum genome has an exceptionally high AT content compared to other Plasmodium species and eukaryotes in general - nearly 80% in coding regions and approaching 90% in non-coding regions. Here, we examine how this phenomenon relates to genome-wide patterns of de novo mutation. Mutation accumulation experiments were performed by sequential cloning of six P. falciparum isolates growing in human erythrocytes in vitro for 4 years, with 279 clones sampled for whole genome sequencing at different time points. Genome sequence analysis of these samples revealed a significant excess of G:C to A:T transitions compared to other types of nucleotide substitution, which would naturally cause AT content to equilibrate close to the level seen across the P. falciparum reference genome (80.6% AT). These data also uncover an extremely high rate of small indel mutation relative to other species, primarily associated with repetitive AT-rich sequences, in addition to larger-scale structural rearrangements focused in antigen-coding var genes. In conclusion, high AT content in P. falciparum is driven by a systematic mutational bias and ultimately leads to an unusual level of microstructural plasticity, raising the question of whether this contributes to adaptive evolution.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkw1259