@article{Johnson01122004,
author = {Johnson, David S. and Davidson, Brad and Brown, Christopher D. and Smith, William C. and Sidow, Arend}, 
title = {Noncoding regulatory sequences of Ciona exhibit strong correspondence between evolutionary constraint and functional importance},
volume = {14}, 
number = {12}, 
pages = {2448-2456}, 
year = {2004}, 
doi = {10.1101/gr.2964504}, 
abstract ={We show that sequence comparisons at different levels of resolution can efficiently guide functional analyses of regulatory regions in the ascidians Ciona savignyi and Ciona intestinalis. Sequence alignments of several tissue-specific genes guided discovery of minimal regulatory regions that are active in whole-embryo reporter assays. Using the Troponin I (TnI) locus as a case study, we show that more refined local sequence analyses can then be used to reveal functional substructure within a regulatory region. A high-resolution saturation mutagenesis in conjunction with comparative sequence analyses defined essential sequence elements within the TnI regulatory region. Finally, we found a significant, quantitative relationship between function and sequence divergence of noncoding functional elements. This work demonstrates the power of comparative sequence analysis between the two Ciona species for guiding gene regulatory experiments.}, 
URL = {http://genome.cshlp.org/content/14/12/2448.abstract}, 
eprint = {http://genome.cshlp.org/content/14/12/2448.full.pdf+html}, 
journal = {Genome Research} 
}