Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum.
Genetic polymorphism and natural selection in the malaria parasite Plasmodium falciparum.
复制标题
DOI：
--
复制
发表时间：
1998-05
期刊：
影响因子：
3.3
通讯作者：
A. Escalante;A. Lal;F. J. Ayala
中科院分区：
文献类型：
--
作者：
A. Escalante;A. Lal;F. J. Ayala
我们研究了10个恶性疟原虫基因座的遗传多态性，这些基因座被认为是特定抗疟疾疫苗的潜在靶点。在子孢子或裂殖子表面表达的蛋白质(AMA-1、CSP、LSA-1、MSP-1、MSP-2和MSP-3)的编码蛋白的基因座(EBA-175、Pfs25、PF48/45和RAP-1)比有性期或体内表达的蛋白更具多态。同义和非同义替换的比较表明，自然选择可能解释了所研究的10个基因座中的7个的多态现象。这一推论依赖于同义替换是中性的假设，我们通过分析一组92个基因座的密码子偏向和G+C含量来检验这一假设。我们发现了A+T丰度增加的总体趋势的证据，但没有突变偏向的证据。虽然同义替换的中立性还没有确定，但这种富含A+T的基因组的趋势不能解释替换的积累，至少在四个基因(AMA-1、CSP、LSA-1和PF48/45)的情况下是如此，因为GLeft和Right箭头C的颠换比预期的更频繁。此外，Tajima试验显示MSP-1和MSP-3基因的多态均为正自然选择，而McDonald-Kreitman试验则显示LSA-1和PF48/45的自然选择。我们的结论是，在编码AMA-1、CSP、LSA-1、MSP-1和Pfs48/45的基因中，有明确的证据表明存在正向自然选择。对于另外四个基因座Eba-175、MSP-2、MSP-3和RAP-1，证据是有限的。Pfs25没有发现自然选择的证据。
We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the Gleft and right arrow C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.