Active conservation of noncoding sequences revealed by three-way species comparisons

Abstract

Human and mouse genomic sequence comparisons are being increasingly used to search for evolutionarily conserved gene regulatory elements. Large-scale human-mouse DNA comparison studies have discovered numerous conserved noncoding sequences of which only a fraction has been functionally investigated A question therefore remains as to whether most of these noncoding sequences are conserved because of functional constraints or are the result of a lack of divergence time.

Figure 1

VISTA plot demonstrating peaks of similarity in the pairwise sequence alignments. Conserved sequences are shown relative to their positions in the human genome (horizontal axes), and their percent identities (50%–100%) are indicated on the vertical axes. The locations of coding exons (blue rectangles) and 5′- and 3′-untranslated regions (UTRs) (turquoise rectangles) are shown above the profile. Horizontal arrows indicate the direction of transcription for each gene. Peaks representing noncoding (red) and UTR (turquoise) sequences fitting the criteria for conserved elements as well as coding sequences (blue) meeting the percentage criteria over their entire length are indicated. The M/D alignment is mapped on the coordinates of the human genome sequence based on matching base pairs in the H/M alignment.