Lineage-specific biology revealed by a finished genome assembly of the mouse.
Lineage-specific biology revealed by a finished genome assembly of the mouse.
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DOI：
10.1371/journal.pbio.1000112
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发表时间：
2009-05-05
期刊：
影响因子：
9.8
通讯作者：
Mouse Genome Sequencing Consortium
中科院分区：
文献类型：
--
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
一个基于克隆完成的小鼠基因组组装揭示了在近期进化过程中广泛的近期序列重复以及某些基因家族在啮齿动物中的特异性扩张。新组装的重复序列包含的蛋白质编码基因大多涉及生殖功能。
小鼠（Mus musculus）是理解人类疾病和发育的首要动物模型。在此我们表明，只有具备一个完成的、高质量的基因组组装，才有可能全面理解小鼠生物学。此处报道的基于克隆完成的小鼠品系C57BL/6J的组装相比早期的MGSCv3基因组草图组装，缺口减少了超过175,000个，新增序列超过139 Mb。在对这个修订后的基因组序列的综合分析中，我们现在能够确定20,210个蛋白质编码基因，比人类基因组预测的（19,042个基因）多出一千多个。此外，我们还鉴定出439种长的非蛋白质编码RNA，有证据表明它们在人类中有转录的直系同源物。我们分析了先前发表的组装中缺失或错误组装的267 Mb序列的复杂且重复的情况，并深入了解了其难以通过全基因组鸟枪法测序和组装的原因。新组装序列中的重复区域往往比已发表草图中的重复区域起源更近，这纠正了我们对小鼠谱系近期进化的最初理解。这些重复区域似乎主要由包含转座元件和重复的蛋白质编码基因的序列区域组成；其中一些可能在小鼠群体中固定，但至少40%的片段重复序列即使在实验室小鼠品系中拷贝数也是可变的。小鼠谱系特异性区域包含3,767个基因，主要来自与生殖功能相关的快速变化的基因家族。因此，完成的小鼠基因组组装极大地提高了我们对啮齿动物特异性生物学的理解，并能够区分与人类共有的祖先生物学功能和不共有的衍生功能。
准确的基因组序列的可用性为现代生物医学研究提供了基石。在此我们描述了小鼠基因组的高质量组装版本Build 36。这个组装是通过比对代表基因组部分的重叠单个克隆而构建的，它提供了比先前组装更完整的图像，因为它增加了许多先前无法获得的啮齿动物特异性序列。这些序列的增加使我们对小鼠的基因组结构和基因组成都有了更深入的了解。特别是，它突出了啮齿动物进化过程中近期的基因重复和某些基因家族的扩张。对小鼠基因组以及小鼠生物学的更好理解将提高小鼠作为人类疾病模型的实用性。
A finished clone-based assembly of the mouse genome reveals extensive recent sequence duplication during recent evolution and rodent-specific expansion of certain gene families. Newly assembled duplications contain protein-coding genes that are mostly involved in reproductive function. The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non–protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not. The availability of an accurate genome sequence provides the bedrock upon which modern biomedical research is based. Here we describe a high-quality assembly, Build 36, of the mouse genome. This assembly was put together by aligning overlapping individual clones representing parts of the genome, and it provides a more complete picture than previous assemblies, because it adds much rodent-specific sequence that was previously unavailable. The addition of these sequences provides insight into both the genomic architecture and the gene complement of the mouse. In particular, it highlights recent gene duplications and the expansion of certain gene families during rodent evolution. An improved understanding of the mouse genome and thus mouse biology will enhance the utility of the mouse as a model for human disease.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1073/pnas.0801383105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Bolliger, Marc F.;Pei, Jimin;Sudhof, Thomas C.
通讯作者：
Sudhof, Thomas C.
影响因子：
3.5
作者：
Dadé, S;Callebaut, I;Monget, P
通讯作者：
Monget, P
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE
影响因子：
4.4
作者：
Birtle Z;Goodstadt L;Ponting C
通讯作者：
Ponting C