Population genomics of the immune evasion (var) genes of Plasmodium falciparum.
Population genomics of the immune evasion (var) genes of Plasmodium falciparum.
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DOI：
10.1371/journal.ppat.0030034
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发表时间：
2007-03
期刊：
影响因子：
6.7
通讯作者：
Day KP
中科院分区：
文献类型：
--
作者：
Barry AE;Leliwa-Sytek A;Tavul L;Imrie H;Migot-Nabias F;Brown SM;McVean GA;Day KP
Var基因编码人类疟原虫恶性疟原虫血液阶段的主要表面抗原（PfEMP1）。每种寄生虫基因组中多达60种不同var基因的差异表达是免疫逃避的基础。我们比较了来自巴布亚新几内亚疟疾流行地区的30个寄生虫分离株和来自广泛地理起源（全球）的59个寄生虫分离株的var基因DBLα结构域的多样性。总的来说，我们获得了8000多个质量控制的DBLα序列。在我们的抽样框架内，全球人口共有895种不同的DBLα“类型”，并且可忽略不计的重叠。这表明，全球范围内的var基因多样性是如此巨大，以至于需要对许多基因组进行测序才能捕捉到其真实程度。相比之下，我们发现185种DBLα类型的PNG多样性要低得多，平均约7%的曲目重叠。虽然我们发现了明显的地理结构，但在巴布亚新几内亚发现的近40%的类型也在来自不同国家的样本中发现，显示出大部分多样性的世界性分布。我们还提供证据表明，重组在维持这些免疫逃避基因中发现的前所未有的多态性水平方面起着关键作用。该群体基因组框架为快速探索var基因的地理多样性提供了一种经济有效的分子流行病学工具。疟疾寄生虫在人类宿主的红细胞中生活了生命周期的一部分，在此期间，被称为PfEMP1的各种抗原家族被放置在表面。PfEMP1变异通过多达60个变异基因的顺序表达而切换。这使得寄生虫能够逃避个体宿主体内的免疫检测，从而在蚊子季节性出现的情况下增加其传播给蚊虫媒介的机会。需要快速评估寄生虫种群var基因多样性的方法来测量抗原多样性并确定与疟疾传播的关系。利用一个专门的框架，我们从同一（巴布亚新几内亚）和不同（全球）种群的寄生虫基因组中完成了var基因的首次系统采样。在全球范围内，没有限制var基因的数量，因为寄生虫很少共享var基因。在巴布亚新几内亚，由于高度共享，var基因数量受到限制，并且大多数只在该人群中发现。重组对PNG变异基因的进化具有重要意义。数据表明，在不同的人群中存在不同的var基因，这可能对疟疾从一个地理区域传播到另一个地理区域产生影响。
Var genes encode the major surface antigen (PfEMP1) of the blood stages of the human malaria parasite Plasmodium falciparum. Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion. We compared the diversity of the DBLα domain of var genes sampled from 30 parasite isolates from a malaria endemic area of Papua New Guinea (PNG) and 59 from widespread geographic origins (global). Overall, we obtained over 8,000 quality-controlled DBLα sequences. Within our sampling frame, the global population had a total of 895 distinct DBLα “types” and negligible overlap among repertoires. This indicated that var gene diversity on a global scale is so immense that many genomes would need to be sequenced to capture its true extent. In contrast, we found a much lower diversity in PNG of 185 DBLα types, with an average of approximately 7% overlap among repertoires. While we identify marked geographic structuring, nearly 40% of types identified in PNG were also found in samples from different countries showing a cosmopolitan distribution for much of the diversity. We also present evidence to suggest that recombination plays a key role in maintaining the unprecedented levels of polymorphism found in these immune evasion genes. This population genomic framework provides a cost effective molecular epidemiological tool to rapidly explore the geographic diversity of var genes. Malaria parasites live in red blood cells of the human host for part of the life cycle, during which a family of diverse antigens known as PfEMP1 are placed on the surface. PfEMP1 variants switch by sequential expression of up to 60 var genes. This allows the parasite to evade immune detection within an individual host, enhancing its chances to be transmitted to the mosquito vector in situations where mosquitoes are seasonally available. Methods to rapidly assess var gene diversity in parasite populations are needed to measure antigenic diversity and define relationships with malaria transmission. Using a specialized framework, we completed the first systematic sampling of var genes from parasite genomes obtained from the same (Papua New Guinea [PNG]) and different (global) populations. Globally, there was no limit to the number of var genes because parasites rarely shared var genes. In PNG, var gene numbers were restricted due to high levels of sharing, and most were only found in that population. Recombination was important to the evolution of var genes in PNG. The data suggest there are distinct var genes in different populations, which may have consequences for the spread of malarial disease from one geographic area to another.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ
DOI：
10.1073/pnas.96.8.4563
发表时间：
1999-04-13
影响因子：
11.1
作者：
Hayward, RE;Tiwari, B;Day, KP
通讯作者：
Day, KP
影响因子：
1.5
作者：
Fowler, EV;Peters, JM;Cheng, Q
通讯作者：
Cheng, Q