PT - JOURNAL ARTICLE AU - Rachel M. Agoglia AU - Hunter B. Fraser TI - Disentangling sources of selection on exonic transcriptional enhancers AID - 10.1101/024000 DP - 2015 Jan 01 TA - bioRxiv PG - 024000 4099 - http://biorxiv.org/content/early/2015/08/05/024000.short 4100 - http://biorxiv.org/content/early/2015/08/05/024000.full AB - In addition to coding for proteins, exons can also impact transcription by encoding regulatory elements such as enhancers. It has been debated whether such features confer heightened selective constraint, or evolve neutrally. We have addressed this question by developing a new approach to disentangle the sources of selection acting on exonic enhancers, in which we model the evolutionary rates of every possible substitution as a function of their effects on both protein sequence and enhancer activity. In three exonic enhancers, we found no significant association between evolutionary rates and effects on enhancer activity. This suggests that despite having biochemical activity, these exonic enhancers have no detectable selective constraint, and thus are unlikely to play a major role in protein evolution.