Abstract

BackgroundDNA 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.ResultsOrigin 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0788-9) contains supplementary material, which is available to authorized users.

Highlights

  • DNA replication initiates on defined genome sites, termed origins

  • Transcription initiation loci in Leishmania are enriched in acetylated histone H3 (H3Ac) [6], and 30 of the 36 origins co-localised with these sites

  • Whether origins are limited to RNA RNA polymerase (Pol) II boundaries is unclear, since on chromosome 27 the origin localised to a divergent strand switch region (SSR) from which an RNA polymerase (RNA Pol) II transcription unit and the RNA Pol I transcribed rRNA genes emanate

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Summary

Introduction

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. In every eukaryote examined to date each linear chromosome is replicated from multiple origins that display variations in frequency and timing of firing. Identification of a consensus origin sequence amongst the multiple mapped sites has proved impossible in most eukaryotes, with the exception of Saccharomyces yeast and its relatives [4]

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