RT Journal
A1 Frith, Martin C.
A1 Ponjavic, Jasmina
A1 Fredman, David
A1 Kai, Chikatoshi
A1 Kawai, Jun
A1 Carninci, Piero
A1 Hayshizaki, Yoshihide
A1 Sandelin, Albin
T1 Evolutionary turnover of mammalian transcription start sites
JF Genome Research 
JO Genome Research 
YR 2006 
FD June 01 
VO 16 
IS 6 
SP 713 
OP 722 
DO 10.1101/gr.5031006 
UL http://genome.cshlp.org/content/16/6/713.abstract 
AB 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 transcriptionfactor-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.