Chromosomal distribution of homologs extracts horizontally transferred genomic regions in Staphylococcus aureus, epidermidis and haemolyticus

Fumihiko Takeuchi, Tadashi Baba, Shinya Watanabe, Keiichi Hiramatsu
Department of Infection Control Science, Juntendo University, Tokyo, 113-8421 Japan

Introduction. Among the staphylococcal species belonging to the Gram-positive bacteria, Staphylococcus aureus is notorious for nosocomial infection due to its virulence and antibiotic resistance, S. epidermidis less virulent commonly exists on human skin, and S. haemolyticus has been the earliest in acquisition of drug resistance among these species. We here compared the genomes of these species in order to study their evolution.
Methods. All of the open reading frames (orfs) from the staphylococcal and related species were classified into "homologs" based on the nucleotide sequence similarity. The orfs with a quality ratio by alignment >=70% were grouped together to form a homolog. In order to determine which homologs were common to staphylococcal species and which homologs were unique, we classified the homologs by their phylogenetic profile, i.e., the pattern of appearance in the three staphylococcal species.
Results. The distribution of the homologs common to staphylococci on each chromosome distinguished the regions by horizontal transfer from those vertically transmitted. The orfs common to the three staphylococcal species were conserved in their sequences and their order on chromosomes, encoded genes fundamental for bacteria, and constituted the "genomic backbone" of each species. On the other hand, we found chromosomal regions with few common orfs, which corresponded to transposons, integrated plasmids, prophages, or other genomic islands. We also found that the region in the downstream of oriC (origin of DNA replication) from 30 kbp down to 0.4--0.6 Mbp were specific to each species, and designated as "oriC environ." The oriC environ included in its right end the staphylococcal cassette chromosome (SCC) which is a mobile genetic element that brings antibiotic resistance to staphylococcal strains.
Discussion. Our chromosomal distribution analysis of homologs could extract the regions transferred horizontally, thus would be a novel method useful for the comparison of related bacterial species. We also found that mutant strains of S. haemolyticus had large deletions of up to 427 kbp within the oriC environ which altered their biochemical properties. Thus the oriC environ is not essential for bacterial viability but characterizes the phenotypes of each species. We think this region was formed by accumulating foreign genes, which suggests a novel mechanism for speciation.
Reference. F. Takeuchi et al. (2005) Whole-genome sequencing of Staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species, J. Bacteriol. 187, 7292--7308.