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Genome wide application of DNA melting analysis

Correspondences between functional and thermodynamic melting properties in a genome are being increasingly employed for ab initio gene finding and for the interpretation of the evolution of genomes. Here we present the first systematic genome wide comparison between biologically coding domains and thermodynamically stable regions. In particular, we develop statistical methods to estimate the reliability of the resulting predictions. Not surprisingly, we find that the success of the approach depends on the difference in GC content between the coding and the non-coding parts of the genome and on the percentage of coding base-pairs in the sequence. These prerequisites vary strongly between species, where we observe no systematic differences between eukaryotes and prokaryotes. We find a number of organisms in which the strong correlation of coding domains and thermodynamically stable regions allows us to identify putative exons or genes to complement existing approaches. In contrast to previous investigations along these lines we have not employed the Poland–Scheraga (PS) model of DNA melting but use the earlier Zimm–Bragg (ZB) model. The Ising-like form of the ZB model can be viewed as an approximation to the PS model, with averaged loop entropies included into the cooperative factor . This results in a speed-up by a factor of 20–100 compared to the Fixman–Freire algorithm for the solution of the PS model. We show that for genomic sequences the resulting systematic errors are negligible compared to the parameterization uncertainty of the models. We argue that for limited computing resources, available CPU power is better invested in broadening the statistical base for genomic investigations than in marginal improvements of the description of the physical melting behavior.