Marques Catarina A, Dickens Nicholas J, Paape Daniel, Campbell Samantha J, McCulloch Richard
The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davis Building, 120 University Place, Glasgow, G12 8TA, UK.
Genome Biol. 2015 Oct 19;16:230. doi: 10.1186/s13059-015-0788-9.
DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania.
Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins.
The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture.
DNA复制起始于特定的基因组位点,即复制起点。在迄今为止所研究的真核生物中,复制起点的使用似乎遵循共同的规则:所有染色体均从多个复制起点开始复制,这些复制起点在起始效率上存在差异,并且是从更大的潜在复制起点库中挑选出来的。为了探究DNA复制的这些特征是否适用于所有真核生物,我们描述了寄生虫利什曼原虫全基因组范围的复制起点定位。
利什曼原虫的复制起点定位表明,相对于已表征的真核生物,其复制起点的使用存在显著差异,因为每条染色体似乎都从单个复制起点开始复制。通过比较两种利什曼原虫,我们发现有证据表明,在进化过程中面对染色体融合或裂变事件时,这种复制起点的单一性得以维持。利什曼原虫复制起点的定位表明,所有复制起点的起始效率相同,并且复制起点所占据的基因组位点与相关的非复制起点位点不同。最后,我们提供证据表明,尽管布氏锥虫的染色体从多个强度可变的复制起点开始复制,但利什曼原虫的复制起点位置与布氏锥虫表现出显著的保守性。
微生物真核生物利什曼原虫中单个复制起点进行染色体复制的证明,对复制起点多样性及相关调控的进化具有启示意义,并且可能解释了利什曼原虫染色体结构中普遍存在的非整倍性。