Extreme mutation bias and high AT content in Plasmodium falciparum.


Hamilton, WL; Claessens, A; Otto, TD; Kekre, M; Fairhurst, RM; Rayner, JC; Kwiatkowski, D; (2016) Extreme mutation bias and high AT content in Plasmodium falciparum. Nucleic acids research. ISSN 0305-1048 DOI: https://doi.org/10.1093/nar/gkw1259

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Abstract

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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 27994033
Web of Science ID: 396055400035
URI: http://researchonline.lshtm.ac.uk/id/eprint/3305832

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