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In many bacterial genomes, the leading and lagging strands have different skews in base composition; for example, an excess of guanosine compared to cytosine on the leading strand. Several factors contribute to these skews since they correlate with both the transcription direction of genes and with their replication direction. The molecular reasons for base composition skews attributable solely to replication direction are not known, but are very strong in some genomes. In particular, we find that Chlamydia genes that have switched their orientation relative to the direction of replication, for example by inversion, acquire the skewed base composition of their new "host" strand. Replication-related skews reflect a directional evolutionary force that causes predictable changes in the base composition of switched genes resulting in increased DNA and amino acid sequence divergence. Additionally, comparisons between related genomes reveal that gene order does not appear to deteriorate randomly, but rather by a series of imperfectly symmetrical translocations across an axis through the origin and termination of replication. Homologous recombination, transposable elements and illegitimate recombination could all have played a part in the genome rearrangements. Irrespective of the exact processes involved, the observation that almost all can be explained by a series of recombination events across the replication axis indicates that replication plays a central role in targeting the position of a translocation. These observations suggest that replication plays a major role in directing genome evolution. The possible role of bioinformatics in relation to these analyses will be discussed.
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