科学家说,发现不同疟原虫种群的共有基因可能有助于疟疾疫苗的开发。
澳大利亚Burnet研究所的Alyssa Barry博士在澳大利亚墨尔本召开的第五届世界科学记者大会上宣布了一项关于疟原虫遗传学研究的成果。
开发疟疾疫苗被证明是困难的,因为疟疾的病原体恶性疟原虫(Plasmodium falciparum)在人体内复制的时候可以瞒过免疫系统。
Barry领导了这项研究。他解释说,当疟原虫感染一个人的红细胞的时候,它会制造一些分子,随后这些分子出现在了血细胞的表面上。它们是提醒免疫系统发动攻击的分子。
然而,疟原虫可以通过表达var基因族中的一个基因(var基因族至多有60个基因)从而切换血细胞表面分子的种类。这会让免疫系统产生混淆,从而使疟原虫得以隐蔽。Barry说:“这增加了疟原虫传播到另外一只蚊子的几率。”
在同一个区域和不同地理区域的疟原虫种群中,var基因各不相同。这种多样性被认为是疟原虫成功的部分原因。然而直到今天之前,这种多样性的程度仍然不清楚。
Barry领导的这组科学家和非洲、巴布亚新几内亚、英国和美国的科学家一起测出了来自巴布亚新几内亚和世界其它地区疟原虫var基因的片段。
他们在仅仅80种疟原虫的样本中总共发现了895个版本的var基因片段。但是在巴布亚新几内亚发现的将近40%的var基因型也出现在了来自其它国家的样本中。Barry说,下一步的研究将是发现疟原虫共有的基因,这可以作为疟疾疫苗的靶标。
世界卫生组织统计表明,全世界每年有大约3亿疟疾病例,这导致超过100万人死亡。大约90%的疟疾死亡病例发生在非洲,其中大多数是儿童。
原始出处:
PLoS Pathog. 2007 March; 3(3): e34.
Population Genomics of the Immune Evasion (var) Genes of Plasmodium falciparum
Alyssa E. Barry1,2¤a*, Aleksandra Leliwa-Sytek1,2¤b, Livingston Tavul3, Heather Imrie1,2, Florence Migot-Nabias4¤c, Stuart M. Brown5, Gilean A. V. McVean6, Karen P. Day1,2¤b
1 Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom, 2 Department of Zoology, University of Oxford, Oxford, United Kingdom, 3 Papua New Guinea Institute for Medical Research, Madang, Papua New Guinea, 4 Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon, 5 Research Computing Resource, New York University School of Medicine, New York, New York, United States of America, 6 Department of Statistics, University of Oxford, Oxford, United Kingdom
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.