並列タイトル等熱帯熱マラリア原虫ケニア西部株においてsurf4.1遺伝子に検出された選択圧、フレームシフト変異、コピー数多型
授与機関名Nagasaki University (長崎大学)
一般注記Background: Plasmodium falciparum SURFIN4.1 is a putative ligand expressed on the merozoite and likely on the infected red blood cell, whose gene was suggested to be under directional selection in the eastern Kenyan population, but under balancing selection in the Thai population. To understand this difference, surf4.1 sequences of westernKenyan P. falciparum isolates were analysed. Frameshift mutations and copy number variation (CNV) were also examined for the parasites from western Kenya and Thailand. Results: Positively significant departures from neutral expectations were detected on the surf4.1 region encoding C-terminus of the variable region 2 (Var2) by 3 population-based tests in the western Kenyan population as similarin the Thai population, which was not covered by the previous analysis for eastern Kenyan population. Significant excess of non-synonymous substitutions per nonsynonymous site over synonymous substitutions per synonymous site was also detected in the Var2 region. Negatively significant departures from neutral expectations was detected on the region encoding Var1 C-terminus consistent to the previous observation in the eastern Kenyan population. Parasites possessing a frameshift mutation resulting a product without intracellular Trp-rich (WR) domains were 22/23in western Kenya and 22/36 in Thailand. More than one copy of surf4.1 gene was detected in western Kenya (4/24), but no CNV was found in Thailand (0/36). Conclusions: The authors infer that the high polymorphism of SURFIN4.1 Var2 C-terminus in both Kenyan and Thaipopulations were shaped-up by diversifying selection and maintained by balancing selection. These phenomena were most likely driven by immunological pressure. Whereas the SURFIN4.1 Var1 C-terminus is suggested to be under directional selection consistent to the previous report for the eastern Kenyan population. Most western Kenyan isolates possess a frameshift mutation that would limit the expression of SURFIN4.1 on the merozoite, but only 60% of Thai isolates possess this frameshift, which would affect the level and type of the selection pressure against this protein as seen in the two extremities of Tajima’s D values for Var1 C-terminus between Kenyan and Thai populations. CNV observed in Kenyan isolates may be a consequence of this frameshift mutation to increase benefits on the merozoite surface.
長崎大学学位論文 学位記番号:博(医歯薬)乙第49号 学位授与年月日:平成29年6月7日
Author: Jesse N. Gitaka, Mika Takeda, Masatsugu Kimura, Zulkarnain Md Idris, Chim W. Chan, James Kongere, Kazuhide Yahata, Francis W. Muregi, Yoshio Ichinose, Akira Kaneko and Osamu Kaneko
Citation: Malaria Journal, 16, 98; 2017
Nagasaki University (長崎大学), 博士(医学) (2017-06-07)
DOIinfo:doi/10.1186/s12936-017-1743-x
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