Evolutionary turnover of mammalian transcription start sites.
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.
Frith
Martin C
MC
Genome Exploration Research Group, RIKEN Genomic Sciences Centre (GSC), RIKEN Yokohama Institute, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Ponjavic
Jasmina
J
Fredman
David
D
Kai
Chikatoshi
C
Kawai
Jun
J
Carninci
Piero
P
Hayashizaki
Yoshihide
Y
Hayshizaki
Yoshihide
Y
Sandelin
Albin
A