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Abstract:
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BACKGROUND:Recent advances in genome sequencing suggest a remarkable
conservation in gene content of mammalian organisms. The similarity in gene repertoire
present in different organisms has increased interest in studying regulatory mechanisms of
gene expression aimed at elucidating the differences in phenotypes. In particular, a
proximal promoter region contains a large number of regulatory elements that control the
expression of its downstream gene. Although many studies have focused on identification of
these elements, a broader picture on the complexity of transcriptional regulation of
different biological processes has not been addressed in mammals. The regulatory complexity
may strongly correlate with gene function, as different evolutionary forces must act on the
regulatory systems under different biological conditions. We investigate this hypothesis by
comparing the conservation of promoters upstream of genes classified in different functional
categories.RESULTS:By conducting a rank correlation analysis between functional annotation
and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we
found a significantly greater conservation of the upstream sequence of genes involved in
development, cell communication, neural functions and signaling processes than those
involved in more basic processes shared with unicellular organisms such as metabolism and
ribosomal function. This observation persists after controlling for G+C content. Considering
conservation as a functional signature, we hypothesize a higher density of cis-regulatory
elements upstream of genes participating in complex and adaptive processes.CONCLUSION:We
identified a class of functions that are associated with either high or low promoter
conservation in mammals. We detected a significant tendency that points to complex and
adaptive processes were associated with higher promoter conservation, despite the fact that
they have emerged relatively recently during evolution. We described and contrasted several
hypotheses that provide a deeper insight into how transcriptional complexity might have been
emerged during evolution. |
