The Fasciola hepatica genome: gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution.

The Fasciola hepatica genome: gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution.
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DOI:
10.1186/s13059-015-0632-2
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发表时间:
2015-04-03
期刊:
影响因子:
12.3
通讯作者:
Paterson S
Paterson S
中科院分区:
生物学1区
文献类型:
--
作者:
Cwiklinski K;Dalton JP;Dufresne PJ;La Course J;Williams DJ;Hodgkinson J;Paterson S

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肝片形吸虫是世界范围内家畜的主要病原体,给农业造成巨大的经济损失,每年有240万人感染肝片形吸虫。在这里,我们提供了一个草案的基因组F。hepatica,我们发现它是已知最大的病原体基因组之一,为1.3 Gb。这种大小不能用基因组复制或单个重复元件的扩增来解释,并且考虑到它可能对传播感染所必需的卵子生产造成的负担,这仍然是一个悖论。尽管有可能通过兼性自花受精进行近亲繁殖,但发现了大量的多态性,这突出了快速适应宿主可用性变化、气候变化或药物或疫苗干预的进化潜力。非同义的多态性升高的寄生虫类群,这可能是特别相关的寄生虫的能力,以适应范围广泛的最终哺乳动物和中间软体动物主机共享的基因。大规模的转录变化,特别是在扩展的蛋白酶和微管蛋白家族,被发现作为寄生虫从肠道迁移,通过腹膜和肝脏成熟的胆管。我们确定了抗氧化和解毒途径的新成员,并通过感染定义了它们的差异表达,这可能解释了不同驱虫药物的阶段特异性疗效。这里描述的基因组分析提供了新的见解,这种重要的病原体的进化,其适应宿主环境和外部选择压力。该分析还为新药和疫苗的研究提供了平台。本文的在线版本(doi:10.1186/s13059-015-0632-2)包含补充材料,可供授权用户使用。
The liver fluke Fasciola hepatica is a major pathogen of livestock worldwide, causing huge economic losses to agriculture, as well as 2.4 million human infections annually. Here we provide a draft genome for F. hepatica, which we find to be among the largest known pathogen genomes at 1.3 Gb. This size cannot be explained by genome duplication or expansion of a single repeat element, and remains a paradox given the burden it may impose on egg production necessary to transmit infection. Despite the potential for inbreeding by facultative self-fertilisation, substantial levels of polymorphism were found, which highlights the evolutionary potential for rapid adaptation to changes in host availability, climate change or to drug or vaccine interventions. Non-synonymous polymorphisms were elevated in genes shared with parasitic taxa, which may be particularly relevant for the ability of the parasite to adapt to a broad range of definitive mammalian and intermediate molluscan hosts. Large-scale transcriptional changes, particularly within expanded protease and tubulin families, were found as the parasite migrated from the gut, across the peritoneum and through the liver to mature in the bile ducts. We identify novel members of anti-oxidant and detoxification pathways and defined their differential expression through infection, which may explain the stage-specific efficacy of different anthelmintic drugs. The genome analysis described here provides new insights into the evolution of this important pathogen, its adaptation to the host environment and external selection pressures. This analysis also provides a platform for research into novel drugs and vaccines. The online version of this article (doi:10.1186/s13059-015-0632-2) contains supplementary material, which is available to authorized users.
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