Zhu Xiaotong, Zhao Zhenjun, Feng Yonghui, Li Peipei, Liu Fei, Liu Jun, Yang Zhaoqing, Yan Guiyun, Fan Qi, Cao Yaming, Cui Liwang
Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China.
Dalian Institute of Biotechnology, Dalian, Liaoning, China.
Infect Genet Evol. 2016 Apr;39:155-162. doi: 10.1016/j.meegid.2016.01.021. Epub 2016 Jan 26.
To investigate the genetic diversity of the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) gene in Southeast Asia, we determined PfAMA1 sequences from 135 field isolates collected from the China-Myanmar border area and compared them with 956 publically available PfAMA1 sequences from seven global P. falciparum populations. This analysis revealed high genetic diversity of PfAMA1 in global P. falciparum populations with a total of 229 haplotypes identified. The genetic diversity of PfAMA1 gene from the China-Myanmar border is not evenly distributed in the different domains of this gene. Sequence diversity in PfAMA1 from the China-Myanmar border is lower than that observed in Thai, African and Oceanian populations, but higher than that in the South American population. This appeared to correlate well with the levels of endemicity of different malaria-endemic regions, where hyperendemic regions favor genetic cross of the parasite isolates and generation of higher genetic diversity. Neutrality tests show significant departure from neutrality in the entire ectodomain and Domain I of PfAMA1 in the China-Myanmar border parasite population. We found evidence supporting a substantial continent-wise genetic structure among P. falciparum populations, with the highest genetic differentiation detected between the China-Myanmar border and the South American populations. Whereas no alleles were unique to a specific region, there were considerable geographical differences in major alleles and their frequencies, highlighting further necessity to include more PfAMA1 alleles in vaccine designs.
为了研究东南亚地区恶性疟原虫顶端膜抗原1(PfAMA1)基因的遗传多样性,我们测定了从中国-缅甸边境地区收集的135份野外分离株的PfAMA1序列,并将其与来自全球7个恶性疟原虫种群的956条公开可用的PfAMA1序列进行比较。该分析揭示了全球恶性疟原虫种群中PfAMA1的高遗传多样性,共鉴定出229种单倍型。中国-缅甸边境地区PfAMA1基因的遗传多样性在该基因的不同结构域中分布不均。中国-缅甸边境地区PfAMA1的序列多样性低于泰国、非洲和大洋洲种群,但高于南美种群。这似乎与不同疟疾流行地区的流行程度密切相关,在高流行地区有利于寄生虫分离株的基因交叉和更高遗传多样性的产生。中性检验表明,中国-缅甸边境寄生虫种群中PfAMA1的整个胞外结构域和结构域I显著偏离中性。我们发现有证据支持恶性疟原虫种群之间存在显著的大陆性遗传结构,在中国-缅甸边境种群和南美种群之间检测到最高的遗传分化。虽然没有特定区域特有的等位基因,但主要等位基因及其频率存在相当大的地理差异,这进一步凸显了在疫苗设计中纳入更多PfAMA1等位基因的必要性。