Genetic Consequences of Programmed Genome Rearrangement
Genetic Consequences of Programmed Genome Rearrangement
复制标题
DOI：
10.1016/j.cub.2012.06.028
复制
发表时间：
2012-08-21
期刊：
影响因子：
9.2
通讯作者：
Amemiya, Chris T.
中科院分区：
文献类型：
--
作者：
Smith, Jeramiah J.;Baker, Carl;Amemiya, Chris T.
七鳃鳗(Petromyzon Marinus)在胚胎发育早期经历了发育程序性基因组重排，导致体细胞中近20%的生殖系DNA缺失。生殖系和胞体的基因组分化是耐人寻味的，因为生殖系发挥着独特的生物学作用，它必须具有进行减数分裂重组的能力和分化为每种细胞类型的能力。这些在进化上必不可少的功能使生殖系与体细胞组织产生了分歧，因为当在体细胞系中错误表达时(例如，在肿瘤发生中)，促进重组和多能性的因素可能会破坏基因组的完整性或对细胞命运的指定。在这里，我们描述了新的七鳃鳗基因组和转录资源的开发，并利用这些资源来识别数百个从体细胞谱系中程序性删除的基因。转录组测序和靶向验证研究进一步证实，体细胞缺失的基因在成年(减数分裂)生殖系和胚胎发生期间原始生殖细胞的发育过程中都具有功能。从缺失区域推断的功能信息表明，发育程序性重排是一种(可能是古老的)生物学策略，确保将多潜能功能分离到生殖系，有效地消除体细胞错误表达的可能性。
The lamprey (Petromyzon marinus) undergoes developmentally programmed genome rearrangements that mediate deletion of similar to 20% of germline DNA from somatic cells during early embryogenesis. This genomic differentiation of germline and soma is intriguing, because the germline plays a unique biological role wherein it must possess the ability to undergo meiotic recombination and the capacity to differentiate into every cell type. These evolutionarily indispensable functions set the germline at odds with somatic tissues, because factors that promote recombination and pluripotency can potentially disrupt genome integrity or specification of cell fate when misexpressed in somatic cell lineages (e.g., in oncogenesis). Here, we describe the development of new genomic and transcriptomic resources for lamprey and use these to identify hundreds of genes that are targeted for programmed deletion from somatic cell lineages. Transcriptome sequencing and targeted validation studies further confirm that somatically deleted genes function both in adult (meiotic) germline and in the development of primordial germ cells during embryogenesis. Inferred functional information from deleted regions indicates that developmentally programmed rearrangement serves as a (perhaps ancient) biological strategy to ensure segregation of pluripotency functions to the germline, effectively eliminating the potential for somatic misexpression.