科学家完成了来自不同大陆的疟疾患者血液中五种间日疟原虫(Plasmodium vivax)的全基因组测序。这些研究结果为帮助科学家将来确定疟疾寄生虫的诸如抗药性等特征，以及不同地域分布的不同病原虫株的差异提供了宝贵的信息。美国凯斯西保留地大学(Case Western Reserve University)以及克利夫兰医学中心勒纳研究所(Cleveland Clinic Lerner Research Institute)的研究人员对8万个SNP进行了研究，这形成了对单一地区间日疟原虫多样性进行研究的关联研究及人口调查的基础。
重要的是，这些成果还证实，从马达加斯加、柬埔寨以及南非疟疾患者身上获得的间日疟原虫在遗传上惊人地相似，很少出现本土适应性的现象。遗传多样性的相对缺乏，其中一个可能的原因就是间日疟原虫出现的历史不长，在全世界的快速传播中没有出现大的遗传缺失或经受自然的选择。第二个可能的原因是在目前的间日疟原虫中存在连续的基因扩散。研究者认为，间日疟原虫现在是一种世界性的寄生虫，可以轻易地通过休眠子形式在全世界传播。
研究人员表示，如果第二个理论成立，那么要消除间日疟原虫的前景就比较悲观了。因为在高水平的基因扩散下，与药物抗性或新的逃逸机制有关的遗传多态性可以在全世界传播，会进一步使控制策略复杂化。
对疟原虫全基因组进行测序是科学家尝试寻找有效根除疟疾的一个新的手段。Nature Genetics在8月5日在线发表了两个研究团队对间日疟原虫的测序成果。在其中一项研究中，研究人员检测了来自西非、南美洲和亚洲不同地理位置的多个间日疟原虫株，并绘出了该物种全球变异性的全基因组图谱。分析显示，间日疟原虫的遗传多样性是遍及全世界的恶性疟原虫(Plasmodium falciparum)的两倍，揭示了间日疟原虫惊人的进化能力，这也给疗法研发带来了新的挑战。
间日疟原虫是在全球广泛分布且快速传播的疟疾寄生虫。据估计每年导致全球2.5亿人患病，造成全球公共健康负担14至40亿美元。在以前的遗传分析中，科学家主要以可在猴子中繁殖的病原虫为研究对象。由于间日疟原虫无法在体外存活，使得相关功能性研究非常困难。科学家实现对直接来自患者的间日疟原虫的基因组测序是一个巨大的研究进步。不过，要理清疟疾的发展、寻找可能的治疗策略、以及了解不同病原虫适应环境以及传播的方式，研究者还需要进行进一步的研究。
Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax
Ernest R. Chan, Didier Menard, Peter H. David, Arsène Ratsimbasoa, Saorin Kim, Pheaktra Chim, Catherine Do, Benoit Witkowski, Odile Mercereau-Puijalon, Peter A. Zimmerman, David Serre
Background An estimated 2.85 billion people live at risk of Plasmodium vivax transmission. In endemic countries vivax malaria causes significant morbidity and its mortality is becoming more widely appreciated, drug-resistant strains are increasing in prevalence, and an increasing number of reports indicate that P. vivax is capable of breaking through the Duffy-negative barrier long considered to confer resistance to blood stage infection. Absence of robust in vitro propagation limits our understanding of fundamental aspects of the parasite's biology, including the determinants of its dormant hypnozoite phase, its virulence and drug susceptibility, and the molecular mechanisms underlying red blood cell invasion.
Methodology/Principal Findings Here, we report results from whole genome sequencing of five P. vivax isolates obtained from Malagasy and Cambodian patients, and of the monkey-adapted Belem strain. We obtained an average 70–400 X coverage of each genome, resulting in more than 93% of the Sal I reference sequence covered by 20 reads or more. Our study identifies more than 80,000 SNPs distributed throughout the genome which will allow designing association studies and population surveys. Analysis of the genome-wide genetic diversity in P. vivax also reveals considerable allele sharing among isolates from different continents. This observation could be consistent with a high level of gene flow among parasite strains distributed throughout the world.
Conclusions Our study shows that it is feasible to perform whole genome sequencing of P. vivax field isolates and rigorously characterize the genetic diversity of this parasite. The catalogue of polymorphisms generated here will enable large-scale genotyping studies and contribute to a better understanding of P. vivax traits such as drug resistance or erythrocyte invasion, partially circumventing the lack of laboratory culture that has hampered vivax research for years.
