RT Journal
A1 Margulies, Elliott H.
A1 Blanchette, Mathieu
A1 NISC Comparative Sequencing Program
A1 Haussler, David
A1 Green, Eric D.
T1 Identification and Characterization of Multi-Species Conserved Sequences
JF Genome Research 
JO Genome Research 
YR 2003 
FD December 01 
VO 13 
IS 12 
SP 2507 
OP 2518 
DO 10.1101/gr.1602203 
UL http://genome.cshlp.org/content/13/12/2507.abstract 
AB Comparative sequence analysis has become an essential component of studies aiming to elucidate genome function. The increasing availability of genomic sequences from multiple vertebrates is creating the need for computational methods that can detect highly conserved regions in a robust fashion. Towards that end, we are developing approaches for identifying sequences that are conserved across multiple species; we call these “Multi-species Conserved Sequences” (or MCSs). Here we report two strategies for MCS identification, demonstrating their ability to detect virtually all known actively conserved sequences (specifically, coding sequences) but very little neutrally evolving sequence (specifically, ancestral repeats). Importantly, we find that a substantial fraction of the bases within MCSs (∼70%) resides within non-coding regions; thus, the majority of sequences conserved across multiple vertebrate species has no known function. Initial characterization of these MCSs has revealed sequences that correspond to clusters of transcription factor-binding sites, non-coding RNA transcripts, and other candidate functional elements. Finally, the ability to detect MCSs represents a valuable metric for assessing the relative contribution of a species' sequence to identifying genomic regions of interest, and our results indicate that the currently available genome sequences are insufficient for the comprehensive identification of MCSs in the human genome.