Abstract
DNA replication initiates from multiple replication origins (ORIs) in eukaryotes. Discovery and characterization of replication origins are essential for a better understanding of the molecular mechanism of DNA replication. In this study, the features of autonomously replicating sequences (ARSs) in Saccharomyces cerevisiae have been comprehensively analyzed as follows. Firstly, we carried out the analysis of the ARSs available in S. cerevisiae S288C. By evaluating the sequence similarity of experimentally established ARSs, we found that 94.32% of ARSs are unique across the whole genome of S. cerevisiae S288C and those with high sequence similarity are prone to locate in subtelomeres. Subsequently, we built a non-redundant dataset with a total of 520 ARSs, which are based on ARSs annotation of S. cerevisiae S288C from SGD and then supplemented with those from OriDB and DeOri databases. We conducted a large-scale comparison of ORIs among the diverse budding yeast strains from a population genomics perspective. We found that 82.7% of ARSs are not only conserved in genomic sequence but also relatively conserved in chromosomal position. The non-conserved ARSs tend to distribute in the subtelomeric regions. We also conducted a pan-genome analysis of ARSs among the S. cerevisiae strains, and a total of 183 core ARSs existing in all yeast strains were determined. We extracted the genes adjacent to replication origins among the 104 yeast strains to examine whether there are differences in their gene functions. The result showed that the genes involved in the initiation of DNA replication, such as orc3, mcm2, mcm4, mcm6, and cdc45, are conservatively located adjacent to the replication origins. Furthermore, we found the genes adjacent to conserved ARSs are significantly enriched in DNA binding, enzyme activity, transportation, and energy, whereas for the genes adjacent to non-conserved ARSs are significantly enriched in response to environmental stress, metabolites biosynthetic process and biosynthesis of antibiotics. In general, we characterized the replication origins from the genome-wide and population genomics perspectives, which would provide new insights into the replication mechanism of S. cerevisiae and facilitate the design of algorithms to identify genome-wide replication origins in yeast.
Highlights
DNA replication is a highly orchestrated process, which is tightly controlled to duplicate the genetic materials into both daughter cells (Bell and Labib, 2016)
Overview of autonomously replicating sequences (ARSs) in S. cerevisiae S288C Reference Genome There are a total of 352 ARSs in S. cerevisiae S288C reference genome available in the SGD database (Supplementary Table 1)
By illustrating the distribution of homologous ARSs in each subset (Supplementary Figure 6), we found that the average number of homologous ARSs in each category are relatively similar, due to distinct ecological niche and various degree of human association of the isolated strains, the data fluctuation range are various from each class, which may underline a key role of human-driven activities in shaping the distribution of ARSs in S. cerevisiae (Strope et al, 2015; Peter et al, 2018)
Summary
DNA replication is a highly orchestrated process, which is tightly controlled to duplicate the genetic materials into both daughter cells (Bell and Labib, 2016). The base composition asymmetry widely exists in bacterial genomes (Lobry, 1996; Rocha et al, 1999; Zhang and Gao, 2017; Quan and Gao, 2019). Based on this phenomenon, some strategies to predict replication origin of chromosomes (oriCs) have been developed, for instance, GC skew (Lobry, 1996), cumulative GC skew (Grigoriev, 1998), skewed oligomers (Salzberg et al, 1998) and Z-curve (Zhang and Zhang, 2014). Considering the distributions of DnaA boxes and the conserved oriCs-adjacent genes in different phyla (Mackiewicz et al, 2004; Luo et al, 2018), the web server Ori-Finder (Gao and Zhang, 2008; Luo et al, 2014) has been developed based on the Z-curve method to predict oriCs in bacteria
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