title: Mutation tendency of mutator Plasmodium berghei with proofreading-deficient DNA polymerase δ.
abstract: In this study, we investigated the mutation tendency of a mutator rodent malaria parasite, Plasmodium berghei, with proofreading-deficient DNA polymerase δ. Wild-type and mutator parasites were maintained in mice for over 24 weeks, and the genome-wide accumulated mutations were determined by high-throughput sequencing. The mutator P. berghei had a significant preference for C/G to A/T substitutions; thus, its genome had a trend towards a higher AT content. The mutation rate was influenced by the sequence context, and mutations were markedly elevated at TCT. Some genes mutated repeatedly in replicate passage lines. In particular, knockout mutations of the AP2-G gene were frequent, which conferred strong growth advantages on parasites during the blood stage but at the cost of losing the ability to form gametocytes. This is the first report to demonstrate a biased mutation tendency in malaria parasites, and its results help to promote our basic understanding of Plasmodium genetics.
authors.affiliation: Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Honma
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, 20-2, Shinkawa 6, Mitaka City, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Niikura
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, 20-2, Shinkawa 6, Mitaka City, Tokyo, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Kobayashi
authors.affiliation: Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Suita, Osaka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.affiliation: Department of Molecular and Cellular Parasitology, Juntendo University, 2-1-1 Hongo, Bunkyo, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mita
authors.affiliation: Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Endo
authors.affiliation: Department of Molecular and Cellular Parasitology, Juntendo University, 2-1-1 Hongo, Bunkyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirai
mesh_terms: D000818:Animals; D004258:DNA Polymerase III / Q000235:genetics*; D016054:DNA, Protozoan / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016002:Discriminant Analysis; D004912:Erythrocytes / Q000469:parasitology; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D009154:Mutation; D010962:Plasmodium berghei / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; D004258:DNA Polymerase III