Expression switching in the stevor and Pfmc-2TM superfamilies in Plasmodium falciparum

Expression switching in the stevor and Pfmc-2TM superfamilies in Plasmodium falciparum
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DOI:
10.1111/j.1365-2958.2007.05767.x
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发表时间:
2007-06-01
影响因子:
3.6
通讯作者:
Templeton, Thomas J.
Templeton, Thomas J.
中科院分区:
生物学2区
文献类型:
--
作者:
Lavazec, Catherine;Sanyal, Sohini;Templeton, Thomas J.

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恶性疟原虫具有两个多基因家族,var和rif,其产物表达于受感染的红细胞表面,其中通过抗原变异,它们有助于疟疾发病和逃避抗体介导的宿主免疫。两个较小基因家族stevor和Pfmc-2 TM的产物也定位于红细胞膜,尽管尚不清楚它们是否经历抗原转换。在此,我们使用基因特异性定量逆转录聚合酶链反应(RT-PCR)来研究恶性疟原虫分离株NF 54的原代和第二代克隆系中stevor和Pfmc-2 TM基因家族的转录模式。我们证明:(i)stevor和Pfmc-2 TM家族的表达是克隆变异的,(ii)stevor和Pfmc-2 TM家族的表达经历转换,和(iii)转换率在不同变体和不同同基因克隆之间以每代高于2%的速率变化。此外,我们发现染色体端粒缺失在克隆系中很常见,并导致一系列的缺失基因型。这些发现为stevor和Pfmc-2 TM基因家族在恶性疟原虫抗原变异中发挥作用提供了证据。
Plasmodium falciparum possesses two multigenic families, var and rif, the products of which are expressed on the surface of infected erythrocytes, where via antigenic variation they contribute to malaria pathogenesis and evasion of antibody-mediated host immunity. The products of two smaller gene families, stevor and Pfmc-2TM, also localize to the erythrocyte membrane, although it is not known if they undergo antigenic switching. Herein we use gene-specific quantitative reverse transcription polymerase chain reaction (RT-PCR) to investigate the transcription pattern of the stevor and Pfmc-2TM gene families, in both primary and second generation clonal lines of the P. falciparum isolate, NF54. We show that: (i) the expression of stevor and Pfmc-2TM families is clonally variant, (ii) the expression of stevor and Pfmc-2TM families undergoes switching, and (iii) switching rates vary among different variants and different isogenic clones at rates higher than 2% per generation. In addition, we show that chromosomal telomeric deletions are common in clonal lines and result in a spectrum of deletion genotypes. These findings provide evidence that the stevor and Pfmc-2TM gene families play a role in P. falciparum antigenic variation.