A comprehensive evaluation of rodent malaria parasite genomes and gene expression.

A comprehensive evaluation of rodent malaria parasite genomes and gene expression.
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DOI:
10.1186/s12915-014-0086-0
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发表时间:
2014-10-30
期刊:
影响因子:
5.4
通讯作者:
Janse CJ
Janse CJ
中科院分区:
生物学2区
文献类型:
--
作者:
Otto TD;Böhme U;Jackson AP;Hunt M;Franke-Fayard B;Hoeijmakers WA;Religa AA;Robertson L;Sanders M;Ogun SA;Cunningham D;Erhart A;Billker O;Khan SM;Stunnenberg HG;Langhorne J;Holder AA;Waters AP;Newbold CI;Pain A;Berriman M;Janse CJ

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啮齿类疟原虫(RMP)被广泛用作人类疟疾的模型。约氏疟原虫、伯氏疟原虫ANKA(PbA)和夏氏疟原虫AS(PcAS)的RMP基因组草案已经发表。虽然这些基因组的可用性对最近的疟疾研究产生了重大影响,但这些基因组高度碎片化,几乎没有人工管理。基因组的片段化性质阻碍了疟原虫基因调控和功能的全基因组分析。我们极大地改进了PbA和PcAS的基因组组装,对毒性寄生虫约氏疟原虫YM基因组进行了新的测序,对其他RMP分离株/株系进行了测序,并对RMP种属内的基因型多样性进行了表征。我们已经产生了RNA-seq数据,并利用它来改进基因模型预测,并提供有关基因表达的定量、全基因组数据。RMP基因组与人类疟原虫恶性疟原虫基因组的比较和RNA-seq作图允许在碱基对分辨率下进行基因注释。全长染色体注释允许一个全面的分类,所有亚端粒多基因家族,包括'疟原虫散布重复基因'(PIR)。pir家族的系统发育分类,结合pir表达模式,表明该家族内的功能多样性。完整的RMP基因组,RNA-seq和基因型多样性数据是基因功能和后基因组分析以及更好地询问疟原虫生物学的优秀和重要资源。夏氏疟原虫分离株之间的基因型多样性使得该物种成为研究基因型-表型关系的极好寄生虫。多基因家族分类的改进将加强对(变体)输出蛋白在毒力和免疫逃避/调节中的作用的研究。本文的在线版本(doi:10.1186/s12915-014-0086-0)包含补充材料,可供授权用户使用。
Rodent malaria parasites (RMP) are used extensively as models of human malaria. Draft RMP genomes have been published for Plasmodium yoelii, P. berghei ANKA (PbA) and P. chabaudi AS (PcAS). Although availability of these genomes made a significant impact on recent malaria research, these genomes were highly fragmented and were annotated with little manual curation. The fragmented nature of the genomes has hampered genome wide analysis of Plasmodium gene regulation and function. We have greatly improved the genome assemblies of PbA and PcAS, newly sequenced the virulent parasite P. yoelii YM genome, sequenced additional RMP isolates/lines and have characterized genotypic diversity within RMP species. We have produced RNA-seq data and utilised it to improve gene-model prediction and to provide quantitative, genome-wide, data on gene expression. Comparison of the RMP genomes with the genome of the human malaria parasite P. falciparum and RNA-seq mapping permitted gene annotation at base-pair resolution. Full-length chromosomal annotation permitted a comprehensive classification of all subtelomeric multigene families including the ‘Plasmodium interspersed repeat genes’ (pir). Phylogenetic classification of the pir family, combined with pir expression patterns, indicates functional diversification within this family. Complete RMP genomes, RNA-seq and genotypic diversity data are excellent and important resources for gene-function and post-genomic analyses and to better interrogate Plasmodium biology. Genotypic diversity between P. chabaudi isolates makes this species an excellent parasite to study genotype-phenotype relationships. The improved classification of multigene families will enhance studies on the role of (variant) exported proteins in virulence and immune evasion/modulation. The online version of this article (doi:10.1186/s12915-014-0086-0) contains supplementary material, which is available to authorized users.
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