Distinguishing Microbial Genome Fragments Based on Their Composition: Evolutionary and Comparative Genomic Perspectives

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It is well known that patterns of nucleotide composition vary within and among genomes, although the reasons why these variations exist are not completely understood. Between-genome compositional variation has been exploited to assign environmental shotgun sequences to their most likely originating genomes, whereas within-genome variation has been used to identify recently acquired genetic material such as pathogenicity islands. Recent sequence assignment techniques have achieved high levels of accuracy on artificial data sets, but the relative difficulty of distinguishing lineages with varying degrees of relatedness, and different types of genomic sequence, has not been examined in depth. We investigated the compositional differences in a set of 774 sequenced microbial genomes, finding rapid divergence among closely related genomes, but also convergence of compositional patterns among genomes with similar habitats. Support vector machines were then used to distinguish all pairs of genomes based on genome fragments 500 nucleotides in length. The nearly 300,000 accuracy scores obtained from these trials were used to construct general models of distinguishability versus taxonomic and compositional indices of genomic divergence. Unusual genome pairs were evident from their large residuals relative to the fitted model, and we identified several factors including genome reduction, putative lateral genetic transfer, and habitat convergence that influence the distinguishability of genomes. The positional, compositional, and functional context of a fragment within a genome has a strong influence on its likelihood of correct classification, but in a way that depends on the taxonomic and ecological similarity of the comparator genome.