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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.

Original publication

DOI

10.1093/nar/gkw1259

Type

Journal article

Journal

Nucleic Acids Res

Publication Date

28/02/2017

Volume

45

Pages

1889 - 1901

Keywords

Base Composition, Gene Expression Regulation, Genome, Protozoan, INDEL Mutation, Mutation, Mutation Rate, Phylogeny, Plasmodium falciparum, Polymorphism, Single Nucleotide, Recombination, Genetic, Reproducibility of Results