科學(xué)家說(shuō),，發(fā)現(xiàn)不同瘧原蟲(chóng)種群的共有基因可能有助于瘧疾疫苗的開(kāi)發(fā),。
澳大利亞Burnet研究所的Alyssa Barry博士在澳大利亞墨爾本召開(kāi)的第五屆世界科學(xué)記者大會(huì)上宣布了一項(xiàng)關(guān)于瘧原蟲(chóng)遺傳學(xué)研究的成果。
開(kāi)發(fā)瘧疾疫苗被證明是困難的,，因?yàn)榀懠驳牟≡w惡性瘧原蟲(chóng)（Plasmodium falciparum）在人體內(nèi)復(fù)制的時(shí)候可以瞞過(guò)免疫系統(tǒng),。
Barry領(lǐng)導(dǎo)了這項(xiàng)研究,。他解釋說(shuō),，當(dāng)瘧原蟲(chóng)感染一個(gè)人的紅細(xì)胞的時(shí)候,，它會(huì)制造一些分子，隨后這些分子出現(xiàn)在了血細(xì)胞的表面上,。它們是提醒免疫系統(tǒng)發(fā)動(dòng)攻擊的分子,。
然而,，瘧原蟲(chóng)可以通過(guò)表達(dá)var基因族中的一個(gè)基因（var基因族至多有60個(gè)基因）從而切換血細(xì)胞表面分子的種類(lèi),。這會(huì)讓免疫系統(tǒng)產(chǎn)生混淆，從而使瘧原蟲(chóng)得以隱蔽,。Barry說(shuō)：“這增加了瘧原蟲(chóng)傳播到另外一只蚊子的幾率,。”
在同一個(gè)區(qū)域和不同地理區(qū)域的瘧原蟲(chóng)種群中，var基因各不相同,。這種多樣性被認(rèn)為是瘧原蟲(chóng)成功的部分原因,。然而直到今天之前，這種多樣性的程度仍然不清楚,。
Barry領(lǐng)導(dǎo)的這組科學(xué)家和非洲,、巴布亞新幾內(nèi)亞、英國(guó)和美國(guó)的科學(xué)家一起測(cè)出了來(lái)自巴布亞新幾內(nèi)亞和世界其它地區(qū)瘧原蟲(chóng)var基因的片段,。
他們?cè)趦H僅80種瘧原蟲(chóng)的樣本中總共發(fā)現(xiàn)了895個(gè)版本的var基因片段。但是在巴布亞新幾內(nèi)亞發(fā)現(xiàn)的將近40%的var基因型也出現(xiàn)在了來(lái)自其它國(guó)家的樣本中,。Barry說(shuō),，下一步的研究將是發(fā)現(xiàn)瘧原蟲(chóng)共有的基因，這可以作為瘧疾疫苗的靶標(biāo),。
世界衛(wèi)生組織統(tǒng)計(jì)表明,，全世界每年有大約3億瘧疾病例，這導(dǎo)致超過(guò)100萬(wàn)人死亡,。大約90%的瘧疾死亡病例發(fā)生在非洲,，其中大多數(shù)是兒童。
原始出處:
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.
