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Craig E Nelson¤, Bradley M Hersh¤ and Sean B Carroll Address: Howard Hughes Medical Institute, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53703, USA. ¤ These authors contributed equally to this work. reviews Correspondence: Craig E Nelson. E-mail: craignelson@wisc.edu Published: 15 March 2004 Genome Biology 2004, 5:R25 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2004/5/4/R25 Received: 3 December 2003 Revised: 9 January 2004 Accepted: 8 February 2004 reports © 2004 Nelson et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any. | Research Open Access The regulatory content of intergenic DNA shapes genome architecture Craig E Nelson Bradley M Hersh and Sean B Carroll Address Howard Hughes Medical Institute University of Wisconsin-Madison 1525 Linden Drive Madison WI 53703 USA. H These authors contributed equally to this work. Correspondence Craig E Nelson. E-mail craignelson@wisc.edu Published 15 March 2004 Genome Biology 2004 5 R25 The electronic version of this article is the complete one and can be found online at http genomebiology.com 2004 5M R25 Received 3 December 2003 Revised 9 January 2004 Accepted 8 February 2004 2004 Nelson et al. licensee BioMed Central Ltd. This is an Open Access article verbatim copying and redistribution of this article are permitted in all media for any purpose provided this notice is preserved along with the article s original URL. Abstract Background Factors affecting the organization and spacing of functionally unrelated genes in metazoan genomes are not well understood. Because of the vast size of a typical metazoan genome compared to known regulatory and protein-coding regions functional DNA is generally considered to have a negligible impact on gene spacing and genome organization. In particular it has been impossible to estimate the global impact if any of regulatory elements on genome architecture. Results To investigate this we examined the relationship between regulatory complexity and gene spacing in Caenorhabditis elegans and Drosophila melanogaster. We found that gene density directly reflects local regulatory complexity such that the amount of noncoding DNA between a gene and its nearest neighbors correlates positively with that gene s regulatory complexity. Genes with complex functions are flanked by significantly more noncoding DNA than genes with simple or housekeeping functions. Genes of low regulatory complexity are associated with approximately the same amount of noncoding DNA in D. melanogaster and C. elegans while loci of high regulatory
