Genomic DNA k-mer spectra: models and modalities

BACKGROUND:The empirical frequencies of DNA k-mers in whole genome sequences provide an interesting perspective on genomic complexity, and the availability of large segments of genomic sequence from many organisms means that analysis of k-mers with non-trivial lengths is now possible.RESULTS:We have studied the k-mer spectra of more than 100 species from Archea, Bacteria, and Eukaryota, particularly looking at the modalities of the distributions. As expected, most species have a unimodal k-mer spectrum. However, a few species, including all mammals, have multimodal spectra. These species coincide with the tetrapods. Genomic sequences are clearly very complex, and cannot be fully explained by any simple probabilistic model. Yet we sought such an explanation for the observed modalities, and discovered that low-order Markov models capture this property (and some others) fairly well.CONCLUSIONS:Multimodal spectra are characterized by specific ranges of values of C+G content and of CpG dinucleotide suppression, a range that encompasses all tetrapods analyzed. Other genomes, like that of the protozoa Entamoeba histolytica, which also exhibits CpG suppression, do not have multimodal k-mer spectra. Groupings of functional elements of the human genome also have a clear modality, and exhibit either a unimodal or multimodal behaviour, depending on the two above mentioned values.