Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN, USA.
Biology Department, Indiana University, Bloomington, IN, USA.
Nat Microbiol. 2022 Jun;7(6):820-830. doi: 10.1038/s41564-022-01127-7. Epub 2022 May 26.
In all organisms, the DNA sequence and the structural organization of chromosomes affect gene expression. The extremely thermophilic crenarchaeon Sulfolobus has one circular chromosome with three origins of replication. We previously revealed that this chromosome has defined A and B compartments that have high and low gene expression, respectively. As well as higher levels of gene expression, the A compartment contains the origins of replication. To evaluate the impact of three-dimensional organization on genome evolution, we characterized the effect of replication origins and compartmentalization on primary sequence evolution in eleven Sulfolobus species. Using single-nucleotide polymorphism analyses, we found that distance from an origin of replication was associated with increased mutation rates in the B but not in the A compartment. The enhanced polymorphisms distal to replication origins suggest that replication termination may have a causal role in their generation. Further mutational analyses revealed that the sequences in the A compartment are less likely to be mutated, and that there is stronger purifying selection than in the B compartment. Finally, we applied the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to show that the B compartment is less accessible than the A compartment. Taken together, our data suggest that compartmentalization of chromosomal DNA can influence chromosome evolution in Sulfolobus. We propose that the A compartment serves as a haven for stable maintenance of gene sequences, while sequences in the B compartment can be diversified.
在所有生物体中，DNA 序列和染色体的结构组织都会影响基因表达。极端嗜热古菌 Sulfolobus 有一条圆形染色体，有三个复制起点。我们之前曾揭示，这条染色体有明确的 A 区和 B 区，分别具有高和低的基因表达水平。A 区除了具有更高水平的基因表达外，还包含复制起点。为了评估三维组织对基因组进化的影响，我们在 11 种 Sulfolobus 物种中，对复制起点和区室化对初级序列进化的影响进行了特征描述。通过单核苷酸多态性分析，我们发现距离复制起点的距离与 B 区而非 A 区的突变率增加有关。复制起点远端增强的多态性表明，复制终止可能在其产生中起因果作用。进一步的突变分析表明，A 区的序列不太可能发生突变，而且比 B 区具有更强的纯化选择。最后，我们应用了转座酶可及染色质的测定（ATAC-seq），结果表明 B 区不如 A 区可接近。总之，我们的数据表明，染色体 DNA 的区室化可以影响 Sulfolobus 中的染色体进化。我们提出，A 区作为稳定维持基因序列的避风港，而 B 区的序列可以多样化。
