Mutation tendency of mutator Plasmodium berghei with proofreading-deficient DNA polymerase δ.

Mutation tendency of mutator Plasmodium berghei with proofreading-deficient DNA polymerase δ.
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突变粒质体的突变趋势与缺陷缺陷的DNA聚合酶δ。

DOI:
10.1038/srep36971
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发表时间:
2016-11-15
期刊:
影响因子:
4.6
通讯作者:
Hirai M
Hirai M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Honma H;Niikura M;Kobayashi F;Horii T;Mita T;Endo H;Hirai M

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在这项研究中,我们研究了一种变基因啮齿类疟原虫,伯氏疟原虫,与校正缺陷的DNA聚合酶δ的突变倾向。将野生型和突变体寄生虫在小鼠中维持超过24周,并通过高通量测序确定全基因组累积突变。变应子伯氏疟原虫对C/G到A/T置换有明显偏好;因此,其基因组具有更高AT含量的趋势。突变率受序列背景的影响,TCT时突变显著升高。一些基因在重复传代系中反复突变。特别是,AP 2-G基因的敲除突变是频繁的,这赋予了强大的生长优势,寄生虫在血液阶段,但在失去形成配子体的能力为代价。这是第一份证明疟疾寄生虫有偏向突变倾向的报告,其结果有助于促进我们对疟原虫遗传学的基本理解。
In this study, we investigated the mutation tendency of a mutator rodent malaria parasite, Plasmodium berghei, with proofreading-deficient DNA polymerase δ. Wild-type and mutator parasites were maintained in mice for over 24 weeks, and the genome-wide accumulated mutations were determined by high-throughput sequencing. The mutator P. berghei had a significant preference for C/G to A/T substitutions; thus, its genome had a trend towards a higher AT content. The mutation rate was influenced by the sequence context, and mutations were markedly elevated at TCT. Some genes mutated repeatedly in replicate passage lines. In particular, knockout mutations of the AP2-G gene were frequent, which conferred strong growth advantages on parasites during the blood stage but at the cost of losing the ability to form gametocytes. This is the first report to demonstrate a biased mutation tendency in malaria parasites, and its results help to promote our basic understanding of Plasmodium genetics.
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