Allele frequency-based and polymorphism-versus-divergence indices of balancing selection in a new filtered set of polymorphic genes in Plasmodium falciparum.
Allele frequency-based and polymorphism-versus-divergence indices of balancing selection in a new filtered set of polymorphic genes in Plasmodium falciparum.
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DOI：
10.1093/molbev/msq119
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发表时间：
2010-10
影响因子：
10.7
通讯作者：
Conway DJ
中科院分区：
文献类型：
--
作者：
Ochola LI;Tetteh KK;Stewart LB;Riitho V;Marsh K;Conway DJ
在地方性病原体的特定基因座上进行平衡选择的特征可以识别自然获得性免疫的候选靶点。在疟疾寄生虫中，几种领先的候选疫苗在接受几次中性测试时令人信服地显示出这样的签名，但发现受类似程度的选择影响的新靶点的速度一直很慢。最近对26个恶性疟原虫裂殖子阶段基因的研究表明，所有基因中的一小部分处于这种选择之下，这些基因以前没有被优先列为候选疫苗，其中只有一个基因(座位PF10_0348)显示出强烈的特征。因此，为了集中发现多态基因，我们扫描了所有可用的恶性疟原虫实验室品系的鸟枪式基因组序列数据，并选择了每千个碱基超过5个单核苷酸多态的6个基因座(包括Pf10348)，用于在肯尼亚群体中进行深入的基于频率的分析(每个基因座的等位基因样本量为50)，并比较群体多样性(π)和种间差异(K)与黑猩猩寄生虫雷氏疟原虫的哈德逊-克莱特曼-阿古德(HKA)比率。其中3个(类msp3/6基因PF10_0348和PF10_0355以及SURF4.1基因PFD1160w)表现出极高的田岛D指数、FU指数和李氏F指数的正值，并具有最高的HKA比率，表明它们处于平衡选择状态，应优先研究其蛋白产物作为候选免疫靶标。结合以前的结果，现在有强有力的证据表明，高HKA比率(以及与频率无关的沃特森的θ/K比率)预示着田岛D的高值。因此，当一个物种内的基因组序列数量较少时，前者提供了用于全基因组筛选的价值，或者与田岛的D结合作为对大群体基因组样本的2D测试。
Signatures of balancing selection operating on specific gene loci in endemic pathogens can identify candidate targets of naturally acquired immunity. In malaria parasites, several leading vaccine candidates convincingly show such signatures when subjected to several tests of neutrality, but the discovery of new targets affected by selection to a similar extent has been slow. A small minority of all genes are under such selection, as indicated by a recent study of 26 Plasmodium falciparum merozoite-stage genes that were not previously prioritized as vaccine candidates, of which only one (locus PF10_0348) showed a strong signature. Therefore, to focus discovery efforts on genes that are polymorphic, we scanned all available shotgun genome sequence data from laboratory lines of P. falciparum and chose six loci with more than five single nucleotide polymorphisms per kilobase (including PF10_0348) for in-depth frequency–based analyses in a Kenyan population (allele sample sizes >50 for each locus) and comparison of Hudson–Kreitman–Aguade (HKA) ratios of population diversity (π) to interspecific divergence (K) from the chimpanzee parasite Plasmodium reichenowi. Three of these (the msp3/6-like genes PF10_0348 and PF10_0355 and the surf4.1 gene PFD1160w) showed exceptionally high positive values of Tajima's D and Fu and Li's F indices and have the highest HKA ratios, indicating that they are under balancing selection and should be prioritized for studies of their protein products as candidate targets of immunity. Combined with earlier results, there is now strong evidence that high HKA ratio (as well as the frequency-independent ratio of Watterson's θ/K) is predictive of high values of Tajima's D. Thus, the former offers value for use in genome-wide screening when numbers of genome sequences within a species are low or in combination with Tajima's D as a 2D test on large population genomic samples.
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影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
5.4
作者：
HILL W G;ROBERTSON A
通讯作者：
ROBERTSON A
影响因子：
3.7
作者：
Mwangi, Tabitha Wanja;Fegan, Gregory;Marsh, Kevin
通讯作者：
Marsh, Kevin
影响因子：
56.9
作者：
Joy, DA;Feng, XR;Su, XZ
通讯作者：
Su, XZ
DOI：
10.1016/s0169-4758(96)10077-6
发表时间：
1997-01-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Conway, DJ
通讯作者：
Conway, DJ