Examination of Genome Homogeneity in Prokaryotes Using Genomic Signatures

Background: DNA word frequencies, normalized for genomic AT content, are remarkably stable within prokaryotic genomes and are therefore said to reflect a “genomic signature.” The genomic signatures can be used to phylogenetically classify organisms from arbitrary sampled DNA. Genomic signatures can also be used to search for horizontally transferred DNA or DNA regions subjected to special selection forces. Thus, the stability of the genomic signature can be used as a measure of genomic homogeneity. The factors associated with the stability of the genomic signatures are not known, and this motivated us to investigate further. We analyzed the intra-genomic variance of genomic signatures based on AT content normalization (0th order Markov model) as well as genomic signatures normalized by smaller DNA words (1st and 2nd order Markov models) for 636 sequenced prokaryotic genomes. Regression models were fitted, with intra-genomic signature variance as the response variable, to a set of factors representing genomic properties such as genomic AT content, genome size, habitat, phylum, oxygen requirement, optimal growth temperature and oligonucleotide usage variance (OUV, a measure of oligonucleotide usage bias), measured as the variance between genomic tetranucleotide frequencies and Markov chain approximated tetranucleotide frequencies, as predictors. Principal Findings: Regression analysis revealed that OUV was the most important factor (p