Paired-End Sequence Mapping Detects Extensive Genomic Rearrangement and Translocation during Divergence of Francisella tularensis subsp. tularensis and Francisella tularensis subsp. holarctica Populations

Authors

Michael P. Dempsey, University of Nebraska Medical Center
Joseph Nietfeldt, University of Nebraska-LincolnFollow
Jaques Ravel, The Institute for Genome Research
Steven H. Hinrichs, University of Nebraska Medical CenterFollow
Robert Crawford, Armed Forces Institute of Pathology
Andrew K. Benson, University of Nebraska-LincolnFollow

Date of this Version

2006

Comments

Published in Journal of Bacteriology (2006) 188:16 p. 5904-5914; Copyright 2006 American Society for Microbiology; Used by permission

Abstract

Comparative genome hybridization of the Francisella tularensis subsp. tularensis and F. tularensis subsp. holarctica populations have shown that genome content is highly conserved, with relatively few genes in the F. tularensis subsp. tularensis genome being absent in other F. tularensis subspecies. To determine if organization of the genome differs between global populations of F. tularensis subsp. tularensis and F. tularensis subsp. holarctica, we have used paired-end sequence mapping (PESM) to identify regions of the genome where synteny is broken. The PESM approach compares the physical distances between paired-end sequencing reads of a library of a wild-type reference F. tularensis subsp. holarctica strain to the predicted lengths between the reads based on map coordinates of two different F. tularensis genome sequences. A total of 17 different continuous regions were identified in the F. tularensis subsp. holarctica genome (CR_holarctica) which are noncontiguous in the F. tularensis subsp. tularensis genome. Six of the 17 different CR_holarctica are positioned as adjacent pairs in the F. tularensis subsp. tularensis genome sequence but are translocated in F. tularensis subsp. holarctica, implying that their arrangements are ancestral in F. tularensis subsp. tularensis and derived in F. tularensis subsp. holarctica. PCR analysis of the CR_holarctica in 88 additional F. tularensis subsp. tularensis and F. tularensis subsp. holarctica isolates showed that the arrangements of the CR_holarctica are highly conserved, particularly in F. tularensis subsp. holarctica, consistent with the hypothesis that global populations of F. tularensis subsp. holarctica have recently experienced a periodic selection event or they have emerged from a recent clonal expansion. Two unique F. tularensis subsp. tularensis-like strains were also observed which likely are derived from evolutionary intermediates and may represent a new taxonomic unit.