Abstract
Eukaryotic chromosomes initiate DNA synthesis from multiple replication origins. The machinery that initiates DNA synthesis is highly conserved, but the sites where the replication initiation proteins bind have diverged significantly. Functional comparative genomics is an obvious approach to study the evolution of replication origins. However, to date, the Saccharomyces cerevisiae replication origin map is the only genome map available. Using an iterative approach that combines computational prediction and functional validation, we have generated a high-resolution genome-wide map of DNA replication origins in Kluyveromyces lactis. Unlike other yeasts or metazoans, K. lactis autonomously replicating sequences (KlARSs) contain a 50 bp consensus motif suggestive of a dimeric structure. This motif is necessary and largely sufficient for initiation and was used to dependably identify 145 of the up to 156 non-repetitive intergenic ARSs projected for the K. lactis genome. Though similar in genome sizes, K. lactis has half as many ARSs as its distant relative S. cerevisiae. Comparative genomic analysis shows that ARSs in K. lactis and S. cerevisiae preferentially localize to non-syntenic intergenic regions, linking ARSs with loci of accelerated evolutionary change.
Highlights
The first step in the initiation of DNA synthesis in eukaryotes is the binding of the Origin Recognition Complex (ORC) to the replication origin [1]
The S. cerevisiae replication origins genome map is less than 100% complete as new ARSs are still being identified with each new study
Comparative functional genomics is an obvious approach to addressing questions about the positional conservation and chromosomal determinants of replication origins
Summary
The first step in the initiation of DNA synthesis in eukaryotes is the binding of the Origin Recognition Complex (ORC) to the replication origin [1]. A genome-wide map based on high resolution tiling microarray indicates that there are 401 strong origins and 503 putative weak origins spaced at an average length of ,14 kb in clusters throughout the S. pombe genome [12,13,14]. In this respect, the genomic landscape for replication initiation in S. pombe resembles that of insect and amphibian embryonic cells [15,16]. Studies of additional yeast species that bridge these wide divides would greatly enhance informative evolutionary comparisons
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
