Bacterial genomes lacking long-range correlations may not be modeled by low-order Markov chains: the role of mixing statistics and frame shift of neighboring genes.

We examine the relationship between exponential correlation functions and Markov models in a bacterial genome in detail. Despite the well known fact that Markov models generate sequences with correlation function that decays exponentially, simply constructed Markov models based on nearest-neighbor dimer (first-order), trimer (second-order), up to hexamer (fifth-order), and treating the DNA sequence as being homogeneous all fail to predict the value of exponential decay rate. Even reading-frame-specific Markov models (both first- and fifth-order) could not explain the fact that the exponential decay is very slow. Starting with the in-phase coding-DNA-sequence (CDS), we investigated correlation within a fixed-codon-position subsequence, and in artificially constructed sequences by packing CDSs with out-of-phase spacers, as well as altering CDS length distribution by imposing an upper limit. From these targeted analyses, we conclude that the correlation in the bacterial genomic sequence is mainly due to a mixing of heterogeneous statistics at different codon positions, and the decay of correlation is due to the possible out-of-phase between neighboring CDSs. There are also small contributions to the correlation from bases at the same codon position, as well as by non-coding sequences. These show that the seemingly simple exponential correlation functions in bacterial genome hide a complexity in correlation structure which is not suitable for a modeling by Markov chain in a homogeneous sequence. Other results include: use of the (absolute value) second largest eigenvalue to represent the 16 correlation functions and the prediction of a 10-11 base periodicity from the hexamer frequencies.

Periodic distribution of a putative nucleosome positioning motif in human, nonhuman primates, and archaea: mutual information analysis.

Recently, Trifonov's group proposed a 10-mer DNA motif YYYYYRRRRR as a solution of the long-standing problem of sequence-based nucleosome positioning. To test whether this generic decamer represents a biological meaningful signal, we compare the distribution of this motif in primates and Archaea, which are known to contain nucleosomes, and in Eubacteria, which do not possess nucleosomes. The distribution of the motif is analyzed by the mutual information function (MIF) with a shifted version of itself (MIF profile). We found common features in the patterns of this generic decamer on MIF profiles among primate species, and interestingly we found conspicuous but dissimilar MIF profiles for each Archaea tested. The overall MIF profiles for each chromosome in each primate species also follow a similar pattern. Trifonov's generic decamer may be a highly conserved motif for the nucleosome positioning, but we argue that this is not the only motif. The distribution of this generic decamer exhibits previously unidentified periodicities, which are associated to highly repetitive sequences in the genome. Alu repetitive elements contribute to the most fundamental structure of nucleosome positioning in higher Eukaryotes. In some regions of primate chromosomes, the distribution of the decamer shows symmetrical patterns including inverted repeats.