title: DNA clustering and genome complexity.
abstract: Early global measures of genome complexity (power spectra, the analysis of fluctuations in DNA walks or compositional segmentation) uncovered a high degree of complexity in eukaryotic genome sequences. The main evolutionary mechanisms leading to increases in genome complexity (i.e. gene duplication and transposon proliferation) can all potentially produce increases in DNA clustering. To quantify such clustering and provide a genome-wide description of the formed clusters, we developed GenomeCluster, an algorithm able to detect clusters of whatever genome element identified by chromosome coordinates. We obtained a detailed description of clusters for ten categories of human genome elements, including functional (genes, exons, introns), regulatory (CpG islands, TFBSs, enhancers), variant (SNPs) and repeat (Alus, LINE1) elements, as well as DNase hypersensitivity sites. For each category, we located their clusters in the human genome, then quantifying cluster length and composition, and estimated the clustering level as the proportion of clustered genome elements. In average, we found a 27% of elements in clusters, although a considerable variation occurs among different categories. Genes form the lowest number of clusters, but these are the longest ones, both in bp and the average number of components, while the shortest clusters are formed by SNPs. Functional and regulatory elements (genes, CpG islands, TFBSs, enhancers) show the highest clustering level, as compared to DNase sites, repeats (Alus, LINE1) or SNPs. Many of the genome elements we analyzed are known to be composed of clusters of low-level entities. In addition, we found here that the clusters generated by GenomeCluster can be in turn clustered into high-level super-clusters. The observation of 'clusters-within-clusters' parallels the 'domains within domains' phenomenon previously detected through global statistical methods in eukaryotic sequences, and reveals a complex human genome landscape dominated by hierarchical clustering.
authors.affiliation: Dpto. de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain; Lab. de Bioinformática, Inst. de Biotecnología, Centro de Investigación Biomédica, 18100 Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Dios
authors.affiliation: Dpto. de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain; Lab. de Bioinformática, Inst. de Biotecnología, Centro de Investigación Biomédica, 18100 Granada, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Barturen
authors.affiliation: Dpto. de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain; Lab. de Bioinformática, Inst. de Biotecnología, Centro de Investigación Biomédica, 18100 Granada, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lebrón
authors.affiliation: Plataforma Andaluza de Genómica y Bioinformática (GBPA), Edificio INSUR, Calle Albert Einstein, 41092 Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rueda
authors.affiliation: Dpto. de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain; Lab. de Bioinformática, Inst. de Biotecnología, Centro de Investigación Biomédica, 18100 Granada, Spain.
authors.forename: Michael
authors.initials: M
authors.lastname: Hackenberg
authors.affiliation: Dpto. de Genética, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain; Lab. de Bioinformática, Inst. de Biotecnología, Centro de Investigación Biomédica, 18100 Granada, Spain. Electronic address: oliver@ugr.es.
authors.forename: José L
authors.initials: JL
authors.lastname: Oliver
mesh_terms: D000465:Algorithms; D020087:Alu Elements; D001665:Binding Sites; D002874:Chromosome Mapping / Q000379:methods / Q000706:statistics & numerical data*; D018899:CpG Islands; D004742:Enhancer Elements, Genetic; D005091:Exons; D005809:Genes, Regulator; D015894:Genome, Human; D006801:Humans; D007438:Introns; D020084:Long Interspersed Nucleotide Elements; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014157:Transcription Factors
keywords: Clustering; Genome complexity; Genome elements; Hierarchical clustering