title: Comprehensive analysis of the base composition around the transcription start site in Metazoa.
abstract: BACKGROUND
  The transcription start site of a metazoan gene remains poorly understood, mostly because there is no clear signal present in all genes. Now that several sequenced metazoan genomes have been annotated, we have been able to compare the base composition around the transcription start site for all annotated genes across multiple genomes.
  
  
  RESULTS
  The most prominent feature in the base compositions is a significant local variation in G+C content over a large region around the transcription start site. The change is present in all animal phyla but the extent of variation is different between distinct classes of vertebrates, and the shape of the variation is completely different between vertebrates and arthropods. Furthermore, the height of the variation correlates with CpG frequencies in vertebrates but not in invertebrates and it also correlates with gene expression, especially in mammals. We also detect GC and AT skews in all clades (where %G is not equal to %C or %A is not equal to %T respectively) but these occur in a more confined region around the transcription start site and in the coding region.
  
  
  CONCLUSIONS
  The dramatic changes in nucleotide composition in humans are a consequence of CpG nucleotide frequencies and of gene expression, the changes in Fugu could point to primordial CpG islands, and the changes in the fly are of a totally different kind and unrelated to dinucleotide frequencies.
authors.affiliation: Department of Electrical Engineering (ESAT-SCD), Katholieke Universiteit Leuven, Belgium. stein.aerts@esat.kuleuven.ac.be
authors.forename: Stein
authors.initials: S
authors.lastname: Aerts
authors.forename: Gert
authors.initials: G
authors.lastname: Thijs
authors.forename: Michal
authors.initials: M
authors.lastname: Dabrowski
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
authors.forename: Bart
authors.initials: B
authors.lastname: De Moor
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics; D000818:Animals; D000852:Anopheles / Q000235:genetics; D001482:Base Composition / Q000235:genetics; D002107:Caenorhabditis / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000235:genetics*; D018509:DNA, Helminth / Q000235:genetics; D030541:Databases, Genetic / Q000592:standards; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D020862:GC Rich Sequence / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D051379:Mice; D051381:Rats; D023741:Takifugu / Q000235:genetics; D024363:Transcription Initiation Site; D015027:Zebrafish / Q000235:genetics
chemical_list: D018509:DNA, Helminth; D004247:DNA