A comprehensive genome-wide map of autonomously replicating sequences in a naive genome.
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.
Liachko
Ivan
I
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
Bhaskar
Anand
A
Lee
Chanmi
C
Chung
Shau Chee Claire
SC
Tye
Bik-Kwoon
BK
Keich
Uri
U
D001483:Base Sequence; D004271:DNA, Fungal; D016681:Genome, Fungal; D007716:Kluyveromyces / Q000235:genetics; D008969:Molecular Sequence Data; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics
D004271:DNA, Fungal