Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.
Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.
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DOI：
10.1093/gbe/evz015
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发表时间：
2019-02-01
影响因子：
3.3
通讯作者：
Lyons, Eric
中科院分区：
文献类型：
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作者：
Castillo, Andreina I.;Nelson, Andrew D. L.;Lyons, Eric
疟原虫是了解核苷酸组成如何影响突变，多样化和适应的有价值的模型。没有其他观察到的真核生物在基因组鸟嘌呤-胞嘧啶（GC）含量方面经历了如此大的变化，如疟原虫属中所见（在35-40百万年内约为30%）。虽然已知突变偏差会影响人类感染性间日疟原虫和恶性疟原虫中的GC含量，但没有研究表明不同的基因功能类别如何影响全属成分的变化，或者疟原虫GC含量的变化是否是由自然选择驱动的。在这里，我们测试的假设，某些基因的过程和功能驱动疟原虫物种之间的全球GC含量的变化。我们进行了一个大规模的比较基因组分析，使用的基因组和预测的基因的17个疟原虫物种，涵盖了广泛的基因组GC含量范围。对基因GC含量进行排序并分成十个相等大小的分位数，然后评估其功能富集类别。与基因类别选择可能驱动基因组GC含量一致，跨膜蛋白在极端GC含量分位数（Q1和Q10）内富集。具体而言，变异表面抗原，主要与脊椎动物免疫系统相互作用，表现出倾斜的GC含量分布相比，其他跨膜蛋白。虽然一个明确的因果关系连接GC含量，表达和阳性选择内变异表面抗原间日疟原虫，伯氏疟原虫，恶性疟原虫不能建立，我们发现，无论基因组核苷酸组成，基因GC含量和表达呈正相关，在滋养体阶段。总的来说，这些数据表明，除了突变的偏见，功能蛋白类驱动疟原虫GC含量的变化。
Plasmodium parasites are valuable models to understand how nucleotide composition affects mutation, diversification, and adaptation. No other observed eukaryotes have undergone such large changes in genomic Guanine-Cytosine (GC) content as seen in the genus Plasmodium (approximate to 30% within 35-40 Myr). Although mutational biases are known to influence GC content in the human-infective Plasmodium vivax and Plasmodium falciparum; no study has addressed how different gene functional classes contribute to genus-wide compositional changes, or if Plasmodium GC content variation is driven by natural selection. Here, we tested the hypothesis that certain gene processes and functions drive variation in global GC content between Plasmodium species. We performed a large-scale comparative genomic analysis using the genomes and predicted genes of 17 Plasmodium species encompassing a wide genomic GC content range. Genic GC content was sorted and divided into ten equally sized quantiles that were then assessed for functional enrichment classes. In agreement that selection on gene classes may drive genomic GC content, trans-membrane proteins were enriched within extreme GC content quantiles (Q1 and Q10). Specifically, variant surface antigens, which primarily interact with vertebrate immune systems, showed skewed GC content distributions compared with other trans-membrane proteins. Although a definitive causation linking GC content, expression, and positive selection within variant surface antigens from Plasmodium vivax, Plasmodium berghei, and Plasmodium falciparum could not be established, we found that regardless of genomic nucleotide composition, genic GC content and expression were positively correlated during trophozoite stages. Overall, these data suggest that, alongside mutational biases, functional protein classes drive Plasmodium GC content change.