Department of Genetics and Evolution, The University of Adelaide, North Tce, Adelaide, Australia.
PLoS Comput Biol. 2018 Apr 20;14(4):e1006091. doi: 10.1371/journal.pcbi.1006091. eCollection 2018 Apr.
The forces driving the accumulation and removal of non-coding DNA and ultimately the evolution of genome size in complex organisms are intimately linked to genome structure and organisation. Our analysis provides a novel method for capturing the regional variation of lineage-specific DNA gain and loss events in their respective genomic contexts. To further understand this connection we used comparative genomics to identify genome-wide individual DNA gain and loss events in the human and mouse genomes. Focusing on the distribution of DNA gains and losses, relationships to important structural features and potential impact on biological processes, we found that in autosomes, DNA gains and losses both followed separate lineage-specific accumulation patterns. However, in both species chromosome X was particularly enriched for DNA gain, consistent with its high L1 retrotransposon content required for X inactivation. We found that DNA loss was associated with gene-rich open chromatin regions and DNA gain events with gene-poor closed chromatin regions. Additionally, we found that DNA loss events tended to be smaller than DNA gain events suggesting that they were able to accumulate in gene-rich open chromatin regions due to their reduced capacity to interrupt gene regulatory architecture. GO term enrichment showed that mouse loss hotspots were strongly enriched for terms related to developmental processes. However, these genes were also located in regions with a high density of conserved elements, suggesting that despite high levels of DNA loss, gene regulatory architecture remained conserved. This is consistent with a model in which DNA gain and loss results in turnover or "churning" in regulatory element dense regions of open chromatin, where interruption of regulatory elements is selected against.
推动非编码 DNA 积累和去除，最终导致复杂生物基因组大小进化的力量与基因组结构和组织密切相关。我们的分析提供了一种新的方法，可以在各自的基因组环境中捕获谱系特异性 DNA 增益和缺失事件的区域变化。为了进一步了解这种联系，我们使用比较基因组学来鉴定人类和小鼠基因组中全基因组的个体 DNA 增益和缺失事件。我们专注于 DNA 增益和缺失的分布、与重要结构特征的关系以及对生物过程的潜在影响，发现常染色体中，DNA 增益和缺失都遵循单独的谱系特异性积累模式。然而，在两种物种中，X 染色体都特别富含 DNA 增益，这与 X 染色体失活所需的高 L1 反转录转座子含量一致。我们发现 DNA 缺失与富含基因的开放染色质区域相关，而 DNA 增益事件与基因贫乏的封闭染色质区域相关。此外，我们发现 DNA 缺失事件往往小于 DNA 增益事件，这表明由于其减少了中断基因调控结构的能力，它们能够在富含基因的开放染色质区域中积累。GO 术语富集表明，小鼠缺失热点强烈富集与发育过程相关的术语。然而，这些基因也位于具有高保守元件密度的区域，这表明尽管存在高水平的 DNA 丢失，但基因调控结构仍然保持保守。这与一个模型一致，即 DNA 增益和缺失导致富含调节元件的开放染色质的密集区域中的“转换”或“搅动”，在这些区域中，调节元件的中断被选择。
