Three Periods Of Regulatory Innovation
On-line Supplement: Three Periods Of Regulatory Innovation During Vertebrate Evolution
Genome Browser Tracks
Links in this section will allow you to visualize the sets of CNEEs in the UCSC genome browser. When you click on the link you will be taken to the browser for that species and one of the tracks towards the top titled "Conserved Non-exonic Elements" and subtitled "CNEEs" will show the CNEES we used in this study. If you click on a CNEE in the browser, you will see a number that corresponds to the branch of origin for that CNEE. This image can be used to convert the number to a branch.
Click here to load a track with all human CNEEs along with their branch of origin (hg18 assembly)
Click here to load a track with all human CNEEs along with their branch of origin (mapped to the hg19 assembly)
Click here to load a track with all mouse CNEEs along with their branch of origin (mm9 assembly)
Click here to load a track with all cow CNEEs along with their branch of origin (bosTau4 assembly)
Click here to load a track with all stickleback CNEEs along with their branch of origin (gasAcu1 assembly)
Click here to load a track with all medaka CNEEs along with their branch of origin (oryLat2 assembly)
Files To Download
We realize that along with visualizing data sets in the browser, it can be useful to have raw data files available. These raw data files are in bed format. The "Score" column in the bed file holds a number that represents the inferred branch of origin for that CNEE. This image can be used to convert the number to a branch. The files have been compressed with gzip and are therefore named "exampleName.bed.gz".
Click here to download the human CNEEs as a gzipped bed file (hg18 assembly)
Click here to download the human CNEEs as a gzipped bed file (mapped to the hg19 assembly)
Click here to download the mouse CNEEs as a gzipped bed file (mm9 assembly)
Click here to download the cow CNEEs as a gzipped bed file (bosTau4 assembly)
Click here to download the stickleback CNEEs as a gzipped bed file (gasAcu1 assembly)
Click here to download the medaka CNEEs as a gzipped bed file (oryLat2 assembly)
Enrichment
A quick guide to see the difference in enrichments between ancient and recent human CNEEs using the GREAT Webserver:
- Download this bed file of ancient human CNEEs (present in the human-stickleback ancestor; assembly is hg18)
- Download this bed file of more recent human CNEEs (originating after the human lineage split with mouse; assembly is hg18)
- Go to the GREAT Webserver
- Select hg18 for the assembly
- Upload the bed file of ancient CNEEs as the test regions
- Click "Submit" at the bottom
- You will be presented with very significant enrichments for transcription factors and developmental genes in the first three tables, which are based on Gene Ontology terms
- Repeat steps 3 through 6 with the bed file of recent CNEEs instead of the ancient ones
- The enrichments are not as strong with this small set of recent CNEEs so click the yellow box named "Show controls" next to "Global table controls"
- Enter 1.2 for "Minimum Region-based Fold Enrichment" and press "Set"
- Enter 0.01 for "FDR threshold" and press "Set"
- Select "Significant By Region-based Binomial"
- Look at the first three tables that are based on Gene Ontology terms and note that these more recent CNEEs are no longer strongly enriched for occurring near transcription factors and developmental genes.
Reference
Three Periods of Regulatory Innovation During Vertebrate Evolution.
Craig B. Lowe, Manolis Kellis, Adam Siepel, Brian J. Raney, Michele Clamp, Sofie R. Salama, David M. Kingsley, Kerstin Lindblad-Toh, David Haussler.
Science. 2011 Aug;333(6045):1019-1024.
