Science：全基因组测序探究疟疾传播机制

  近日，发表在国际杂志Science上的一篇研究论文中，来自加拿大西蒙弗雷泽大学等处的研究人员对可传播疟疾的16种按蚊进行了遗传测序，从而为揭示人类为何对其易感提供了新的思路和线索。
  文章中，研究者Cedric Chauve表示，我们利用计算机方法来重新构建蚊子祖先的基因组，并且分析在过去1亿年的过程中蚊子祖先染色体的进化情况；目的在于理解其染色体的进化过程，从而为揭开和疟疾相关的人类机体适应性机制提供帮助，同时研究人员也希望确定不同蚊子种间的遗传差异。
  在不同蚊子种群之间仅有按蚊会向人类传播疟疾，按蚊是疟疾的有效携带者，这就要求研究人员需要深入揭示是什么样的遗传可塑性引发按蚊机体关键特性的突变从而使其具有疟疾传播能力。研究者补充道，这是一项非常有挑战性的研究计划，因为在没有获得其它种的精确研究数据的前提下，目前我们并不能对灭绝很久的蚊子祖先进行全基因组测序。
  这项大型研究包括了来自全世界的100多名生物学家、免疫学家、感染性疾病专家等；当在疟疾控制上初得成效之时，对16种按蚊基因组的测序或可帮助研究人员进一步深入理解传播疟疾的按蚊基因组的适应性机制，对于后期开发出更有效预防疟疾传播的新型技术提供了一定的研究数据和技术保障。（转化医学网360zhyx.com）
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Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance
Science DOI: 10.1126/science.1260403
Sachel Mok1, Elizabeth A. Ashley2,3, Pedro E. Ferreira1, Lei Zhu1, Zhaoting Lin1, Tomas Yeo1, Kesinee Chotivanich4, Mallika Imwong4, Sasithon Pukrittayakamee5, Mehul Dhorda3,6,7, Chea Nguon8, Pharath Lim8,9, Chanaki Amaratunga9, Seila Suon8, Tran Tinh Hien10, Ye Htut11, M. Abul Faiz12, Marie A. Onyamboko13, Mayfong Mayxay14,15, Paul N. Newton2,3,14, Rupam Tripura2, Charles J. Woodrow2,3, Olivo Miotto2,16,17, Dominic P. Kwiatkowski16,17, François Nosten2,18, Nicholas P. J. Day2,3, Peter R. Preiser1, Nicholas J. White2,3, Arjen M. Dondorp2,3, Rick M. Fairhurst9, Zbynek Bozdech1,*
Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. Here we analyze the in-vivo transcriptomes of 1,043 P. falciparum isolates from patients with acute malaria, and show that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin resistant parasites remain in a state of decelerated development at the young ring stage while their upregulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion.