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Genome Res. 2006 Jun;16(6):713-22. Epub 2006 May 10.

Evolutionary turnover of mammalian transcription start sites.

Author information

  • 1Genome Exploration Research Group, RIKEN Genomic Sciences Centre (GSC), RIKEN Yokohama Institute, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.

Erratum in

  • Genome Res. 2006 Jul;16(7):947. Hayshizaki, Yoshihide [corrected to Hayashizaki, Yoshihide].


Alignments of homologous genomic sequences are widely used to identify functional genetic elements and study their evolution. Most studies tacitly equate homology of functional elements with sequence homology. This assumption is violated by the phenomenon of turnover, in which functionally equivalent elements reside at locations that are nonorthologous at the sequence level. Turnover has been demonstrated previously for transcription-factor-binding sites. Here, we show that transcription start sites of equivalent genes do not always reside at equivalent locations in the human and mouse genomes. We also identify two types of partial turnover, illustrating evolutionary pathways that could lead to complete turnover. These findings suggest that the signals encoding transcription start sites are highly flexible and evolvable, and have cautionary implications for the use of sequence-level conservation to detect gene regulatory elements.

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