Evolutionary and biomedical insights from a marmoset diploid genome assembly.
Evolutionary and biomedical insights from a marmoset diploid genome assembly.
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DOI：
10.1038/s41586-021-03535-x
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发表时间：
2021-06
期刊：
影响因子：
64.8
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Yang C;Zhou Y;Marcus S;Formenti G;Bergeron LA;Song Z;Bi X;Bergman J;Rousselle MMC;Zhou C;Zhou L;Deng Y;Fang M;Xie D;Zhu Y;Tan S;Mountcastle J;Haase B;Balacco J;Wood J;Chow W;Rhie A;Pippel M;Fabiszak MM;Koren S;Fedrigo O;Freiwald WA;Howe K;Yang H;Phillippy AM;Schierup MH;Jarvis ED;Zhang G
二倍体生物的两个单倍型序列的准确和完整组装对于理解变异在基因组功能、表型和疾病中的作用至关重要。在这里，我们使用三重分类方法，为普通狨猴（Callithrix jacchus）（一种广泛用于生物医学研究的灵长类动物模型系统）提供了一个高质量的二倍体参考基因组，其中两种单倍型在染色体水平上独立组装。两种单倍型之间的全谱杂合性涉及基因组的 1.36%，远高于仅基于单核苷酸杂合性的标准估计所表明的 0.13%。每代每个位点的从头突变率为 0.43×10−8，父系遗传基因组获得的突变数量是母系的两倍。我们的二倍体组装使我们能够发现狨猴 Y 染色体最近性别分化区域的扩展和独特的进化变化。此外，我们还发现了许多具有正选择特征的基因，这些基因可能有助于 Callithrix 生物学特征的进化。尽管有几个基因经历了谱系特异性拷贝数变异或多样化选择，但与大脑相关的基因在狨猴和人类之间高度保守，这对狨猴作为模型系统的使用具有影响。三重组合方法用于为普通狨猴生成完全单倍型解析的二倍体基因组组装，从而深入了解杂合性谱和性别分化区域的进化。
The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes and diseases. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an primate model system that is widely used in biomedical research. The full spectrum of heterozygosity between the two haplotypes involves 1.36% of the genome—much higher than the 0.13% indicated by the standard estimation based on single-nucleotide heterozygosity alone. The de novo mutation rate is 0.43 × 10−8 per site per generation, and the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex-differentiation region and unique evolutionary changes in the marmoset Y chromosome. In addition, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain-related genes were highly conserved between marmosets and humans, although several genes experienced lineage-specific copy number variations or diversifying selection, with implications for the use of marmosets as a model system. A trio-binning approach is used to produce a fully haplotype-resolved diploid genome assembly for the common marmoset, providing insight into the heterozygosity spectrum and the evolution of the sex-differentiation region.
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影响因子：
12.3
作者：
Acuna-Hidalgo R;Veltman JA;Hoischen A
通讯作者：
Hoischen A
影响因子：
64.8
作者：
Zoonomia Consortium
通讯作者：
Zoonomia Consortium
影响因子：
64.8
作者：
通讯作者：
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影响因子：
48
作者：
Chin, Chen-Shan;Peluso, Paul;Schatz, Michael C.
通讯作者：
Schatz, Michael C.
影响因子：
16.6
作者：
Chakraborty, Mahul;Emerson, J. J.;Long, Anthony D.
通讯作者：
Long, Anthony D.