Maintaining replication origins in the face of genomic change

Abstract

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L . waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved.

The Spatiotemporal Program of Replication in the Genome of Lachancea kluyveri

“…We see that all eight centromeres replicate early in S-phase (on average between 34 min for the earliest [Sakl0G] and 39 min for the latest [Sakl0F]), whereas telomeres tend to replicate later in S-phase (on average between 44 min [Sakl0E-right] and 51 min [Sakl0A-left]), as in S. cerevisiae (Raghuraman et al 2001), L. waltii (Di Rienzi et al 2012), and C. albicans (Koren et al 2010). The timing profile in figure 1 shows that for all chromosomes except Sakl0C-left, replication profiles alternate between large regions mostly replicated early and large regions mostly replicated late during S-phase as was already described in S. cerevisiae (McCune et al 2008), although a thorough mathematical analysis of similar data sets concluded that there is no evidence for clustering of origins with similar activation time in S. cerevisiae (Yang et al 2010).…”

“…We compared the relative conservation of our set of 252 origins in L. kluyveri with the sets of 275 and 194 replication origins in S. cerevisiae and in L. waltii , respectively (Alvino et al 2007; Di Rienzi et al 2012). To achieve this goal, we computed all synteny regions between the genome of L. kluyveri and the two other genomes and determined whether origin-containing regions of 8 kb (4 kb on each side of the peak coordinates) in one genome was conserved in synteny and if an origin was also present in the corresponding region of conserved synteny in each of the two other genomes.…”

An autonomously replicating sequence for use in a wide range of budding yeasts

“…(a) Phylogenetic relationships and previously published ACS motifs are shown for S. cerevisiae (Broach et al 1983; Liachko et al 2013), L. waltii (Di Rienzi et al 2012), L. kluyveri (Liachko et al 2011), and K. lactis (Liachko et al 2010). (b) The sequences of the native (ARS) and optimized (OPT) panARS elements are shown.…”

Analysis of ssDNA Gaps and DSBs in Genetically Unstable Yeast Cultures

“…It was then proposed that ssDNA formation at replication origins during nucleotide shortage caused by the treatment with hydroxyurea (HU, an inhibitor of the ribonucleotide reductase) is an evolutionarily conserved process and can be exploited in order to map origins of replication in diverse organisms. Indeed, HU treatment has been used to identify origins of replication in diverse yeast species such as Schizosaccharomyces pombe [2], Lachancea waltii [4], and Saccharomyces bayanus (G. Alvino, M. Dunham, B. Brewer, and M.K.…”