Germline Structural Variations Are Preferential Sites of DNA Replication Timing Plasticity during Development.
Germline Structural Variations Are Preferential Sites of DNA Replication Timing Plasticity during Development.
复制标题
种系结构变异是发育过程中 DNA 复制时间可塑性的优先位点。
DOI：
10.1093/gbe/evz098
复制
发表时间：
2019
影响因子：
3.3
通讯作者：
Koren,Amnon
中科院分区：
文献类型：
--
作者：
Hulke,MichelleL;Siefert,JosephC;Sansam,ChristopherL;Koren,Amnon
DNA复制时间程序在整个发育过程中被调节，也是影响整个基因组突变率分布的主要因素之一。然而，复制时间的诱变影响与其发育可塑性之间的关系尚不清楚。在这里，我们研究了斑马鱼基因组中拷贝数变异（CNVs）和单核苷酸多态性的分布与胚胎发育过程中DNA复制时间变化的关系。我们发现，在发育过程中，CNV位点表现出很强的复制时间可塑性，在早期发育阶段复制明显早，而在更高级的发育阶段复制明显晚。反过来，在发育过程中改变其复制时间的基因组区域比发育恒定区域含有更高比例的CNVs。发育可塑性CNV位点，特别是那些复制时间延迟的CNV位点，富集了簇状原钙粘蛋白，这是一组对神经元发育很重要的基因，在斑马鱼进化过程中经历了广泛的遗传和表观遗传多样化。相比之下，单核苷酸多态性位点在胚胎发育早期一致复制，突出了斑马鱼基因组的独特方面。我们的研究结果揭示了迄今为止未被认识到的发育和进化之间的界面。
The DNA replication timing program is modulated throughout development and is also one of the main factors influencing the distribution of mutation rates across the genome. However, the relationship between the mutagenic influence of replication timing and its developmental plasticity remains unexplored. Here, we studied the distribution of copy number variations (CNVs) and single nucleotide polymorphisms across the zebrafish genome in relation to changes in DNA replication timing during embryonic development in this model vertebrate species. We show that CNV sites exhibit strong replication timing plasticity during development, replicating significantly early during early development but significantly late during more advanced developmental stages. Reciprocally, genomic regions that changed their replication timing during development contained a higher proportion of CNVs than developmentally constant regions. Developmentally plastic CNV sites, in particular those that become delayed in their replication timing, were enriched for the clustered protocadherins, a set of genes important for neuronal development that have undergone extensive genetic and epigenetic diversification during zebrafish evolution. In contrast, single nucleotide polymorphism sites replicated consistently early throughout embryonic development, highlighting a unique aspect of the zebrafish genome. Our results uncover a hitherto unrecognized interface between development and evolution.