Evidence of non-neutral polymorphism in Plasmodium falciparum gamete surface protein genes Pfs47 and Pfs48/45
Evidence of non-neutral polymorphism in Plasmodium falciparum gamete surface protein genes Pfs47 and Pfs48/45
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DOI：
10.1016/j.molbiopara.2007.07.008
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发表时间：
2007-12-01
影响因子：
1.5
通讯作者：
Conway, David J.
中科院分区：
文献类型：
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作者：
Anthony, Thomas G.;Polley, Spencer D.;Conway, David J.
已知疟原虫6-cys蛋白基因家族的特定成员（包括Ps47、Ps48/45和Ps230）的靶向破坏显著影响寄生虫生育力。由于在许多真核生物物种的生育力的关键位点已被证明是强阳性选择下，我们研究了恶性疟原虫（Pfs 36，Pfs 38，Pfs 47和Pfs 48/45）的6-cys蛋白基因家族的四个成员的序列变异，以确定这些位点的遗传变异是否可能具有功能意义。将11株恶性疟原虫实验室分离株的序列多态性与密切相关的物种赖氏疟原虫中各自直系同源物的差异进行了比较，显示Pfs 47和Pfs 48/45（通过McDonald-Kreitman检验）几乎显著偏向种内非同义多态性，但Pfs 36和Pfs 38的结果明显不显著。对恶性疟原虫田间分离株Pfs 47序列多态性的初步分析显示，在地理上不同的种群中，固定指数（F-ST）异常高，与先前对Pfs 48/45的结果相似。因此，Pfs 47和Pfs 48/45通过对来自坦桑尼亚卵囊群体样品的基因的多态性部分进行测序（分析二倍体基因型的方法）来进一步分析。这两个基因表现出较高的近交系数（F-IS）相比，平均I I非连锁微卫星位点。这些结果表明，在这两个基因的等位基因变异可能是功能上显着的影响交配的相互作用，一个假设，可以通过受精实验有针对性的等位基因替换进行测试。(c)2007 Elsevier B. V.保留所有权利。
Targeted disruption of particular members of the Plasmodium 6-cys protein gene family, including Ps47, Ps48/45 and Ps230, is known to dramatically affect parasite fertility. Because loci critical to fertility in many eukaryote species have been shown to be under strong positive selection, we examined sequence variation in four members of the 6-cys protein gene family in Plasmodium falciparum(Pfs36, Pfs38, Pfs47 and Pfs48/45) to determine whether genetic variation in these loci may be of functional significance. Sequence polymorphism among 11 laboratory isolates of P. falciparum was compared with divergence from the respective orthologues in the closely related species P. reichenowi, showing an almost significant skew towards within-species non-synonymous polymorphism in Pfs47 and Pfs48/45 (by the McDonald-Kreitman test) but clearly non-significant results for Pfs36 and Pfs38. A preliminary analysis of Pfs47 sequence polymorphism in field isolates of P.falciparum showed exceptionally high fixation indices (F-ST) among geographically distinct populations, similar to results seen previously for Pfs48/45. Therefore, both Pfs47and Pfs48/45 were further analysed by sequencing polymorphic parts of the genes from a Tanzanian population sample of oocysts (a means of analysing diploid genotypes). Both genes displayed higher inbreeding coefficients (F-IS) compared with the average of I I unlinked microsatellite loci. These results suggest that allelic variation in these two genes may be functionally significant in influencing mating interactions, a hypothesis that could be tested by fertilization experiments with targeted allelic replacement. (c) 2007 Elsevier B.V. All rights reserved.