Mining Bacillus subtilis chromosome heterogeneities using hidden Markov models.
We present here the use of a new statistical segmentation method on the Bacillus subtilis chromosome sequence. Maximum likelihood parameter estimation of a hidden Markov model, based on the expectation-maximization algorithm, enables one to segment the DNA sequence according to its local composition. This approach is not based on sliding windows; it enables different compositional classes to be separated without prior knowledge of their content, size and localization. We compared these compositional classes, obtained from the sequence, with the annotated DNA physical map, sequence homologies and repeat regions. The first heterogeneity revealed discriminates between the two coding strands and the non-coding regions. Other main heterogeneities arise; some are related to horizontal gene transfer, some to t-enriched composition of hydrophobic protein coding strands, and others to the codon usage fitness of highly expressed genes. Concerning potential and established gene transfers, we found 9 of the 10 known prophages, plus 14 new regions of atypical composition. Some of them are surrounded by repeats, most of their genes have unknown function or possess homology to genes involved in secondary catabolism, metal and antibiotic resistance. Surprisingly, we notice that all of these detected regions are a + t-richer than the host genome, raising the question of their remote sources.
Nicolas
Pierre
P
Laboratoire de Mathématique, Informatique et Génome, INRA, Route de Saint-Cyr, F-78026 Versailles cedex, France. nicolas@versailles.inra.fr
Bize
Laurent
L
Muri
Florence
F
Hoebeke
Mark
M
Rodolphe
François
F
Ehrlich
S Dusko
SD
Prum
Bernard
B
Bessières
Philippe
P
D001412:Bacillus subtilis / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D002876:Chromosomes, Bacterial; D004269:DNA, Bacterial / Q000145:classification; D022761:Gene Transfer, Horizontal; D014644:Genetic Variation; D057927:Hydrophobic and Hydrophilic Interactions; D016013:Likelihood Functions; D008242:Lysogeny; D008390:Markov Chains; D012329:RNA, Bacterial / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial