National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research; WHO Collaborating Centre for Tropical Diseases, Shanghai, 200025, China.
National Center for International Research on Tropical Diseases, Ministry of Science and Technology; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, 200025, China.
Infect Dis Poverty. 2018 Nov 13;7(1):118. doi: 10.1186/s40249-018-0493-5.
China has made progress in malaria control and aims to eliminate malaria nationwide, but implementing effective interventions along the border regions remain a huge task. The Plasmodium falciparum cases imported from Southeast Asia has frequently reported especially in the China-Myanmar border (CMB) area. Though, information is scant on P. falciparum genetic variability in this area.
This study reported P. falciparum isolates genome sequence of six clinical isolates in the CMB area. Furthermore, we estimated the nucleotide diversity, Watterson's estimator and Tajima's D value for the whole genome mutation rate in slide window.
Our data were aligned onto 96.05-98.61% of the reference 3D7 genome in high fold coverages. Principal component analysis result showed that P. falciparum clustered generally according to their geographic origin. A total of 91 genes were identified as positive selection with Ka/Ks ratio significantly higher than 1, and most of them were multigene families encoding variant surface antigens (VSAs) such as var, rif and stevor. The enrichment of the positive selection on VSA genes implied that the environment complexity subjected CMB's P. falciparum to more pressure for survival.
Our research suggests that greater genetic diversity in CMB area and the positive selection signals in VSA genes, which allow P. falciparum to fit the host immune system well and aggravate the difficulty of treatment. Meanwhile, results obtained from this study will provide the fundamental basis for P. falciparum population genomic research in CMB area.
中国在疟疾控制方面取得了进展,目标是在全国范围内消除疟疾,但在边境地区实施有效的干预措施仍然是一项艰巨的任务。从东南亚输入的恶性疟原虫病例,特别是在中国-缅甸边境(CMB)地区时有报告。然而,关于该地区恶性疟原虫遗传变异的信息很少。
本研究报告了 CMB 地区 6 例临床分离株的恶性疟原虫基因组序列。此外,我们还估计了全基因组突变率在滑动窗口中的核苷酸多样性、Watterson 估计值和 Tajima 的 D 值。
我们的数据在高覆盖率下与参考 3D7 基因组的 96.05-98.61%对齐。主成分分析结果表明,恶性疟原虫通常根据其地理起源聚类。共鉴定出 91 个正选择基因,Ka/Ks 比值明显高于 1,其中大多数是多基因家族,编码变异表面抗原(VSAs),如 var、rif 和 stevor。VSA 基因中阳性选择的富集表明,CMB 的恶性疟原虫所处的环境复杂性使其面临更大的生存压力。
我们的研究表明,CMB 地区的遗传多样性更大,VSA 基因中的阳性选择信号更多,这使得恶性疟原虫能够很好地适应宿主免疫系统,加重治疗难度。同时,本研究的结果将为 CMB 地区恶性疟原虫群体基因组研究提供基础。