title: Housekeeping genes tend to show reduced upstream sequence conservation.
abstract: BACKGROUND
  Understanding the constraints that operate in mammalian gene promoter sequences is of key importance to understand the evolution of gene regulatory networks. The level of promoter conservation varies greatly across orthologous genes, denoting differences in the strength of the evolutionary constraints. Here we test the hypothesis that the number of tissues in which a gene is expressed is related in a significant manner to the extent of promoter sequence conservation.
  
  
  RESULTS
  We show that mammalian housekeeping genes, expressed in all or nearly all tissues, show significantly lower promoter sequence conservation, especially upstream of position -500 with respect to the transcription start site, than genes expressed in a subset of tissues. In addition, we evaluate the effect of gene function, CpG island content and protein evolutionary rate on promoter sequence conservation. Finally, we identify a subset of transcription factors that bind to motifs that are specifically over-represented in housekeeping gene promoters.
  
  
  CONCLUSIONS
  This is the first report that shows that the promoters of housekeeping genes show reduced sequence conservation with respect to genes expressed in a more tissue-restricted manner. This is likely to be related to simpler gene expression, requiring a smaller number of functional cis-regulatory motifs.
authors.affiliation: Centre for Genomic Regulation, Dr Aiguader 88, Barcelona 08003, Spain.
authors.forename: Domènec
authors.initials: D
authors.lastname: Farré
authors.forename: Nicolás
authors.initials: N
authors.lastname: Bellora
authors.forename: Loris
authors.initials: L
authors.lastname: Mularoni
authors.forename: Xavier
authors.initials: X
authors.lastname: Messeguer
authors.forename: M Mar
authors.initials: MM
authors.lastname: Albà
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D018899:CpG Islands; D019143:Evolution, Molecular; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic