Figure 1

Identification of three highly conserved non-coding regions in tetrapods and a lobe-finned fish. (A) Sequence alignment of the genomic region critical for Grem1 expression in mouse limb buds [7] using the ECR browser with the mouse genome release 9 (mm9) as reference genome. The critical genomic region on mouse chromosome 2 is shown in centromeric (CEN) to telomeric (TEL) orientation and is located downstream of the Grem1 coding exons. As the critical genomic region is part of the Fmn1 locus, the interspersed Fmn1 coding exons are indicated as open boxes in the scheme. Three blocks of highly conserved non-coding sequences were identified (HMCO1-3) and are indicated in blue. Conserved coding regions are indicated in black and non-coding regions conserved ≥74% over ≥100 bp are coloured salmon. The peak detected in the region of HMCO1 in the zebrafish genome corresponds to Fmn1 exon 22. Regions consisting of repetitive sequences are shown in green (see Additional file 2). (B) Conserved linkage between the Grem1 and Fmn1 loci in vertebrates. Increased intergenic distances correlate with the presence of HMCO regions in tetrapods and coelacanth in contrast to ray-finned fishes. The phylogenetic tree analysis was done with the UCSC multiple alignment functions to align the 3' part of the Fmn1 locus and the Grem1 locus from different species. Open boxes represent the orthologous Fmn1 coding exons 19 and 22, black box represents Grem1 coding exon 2. The intergenic distances between Fmn1 orthologous exon 22 and Grem1 coding exon 2 are indicated to the right of the scheme. ENSEMBL genomes used for alignment: mouse: M. musculus (mm10); human: H. sapiens (hg19); chimpanzee: P. troglodytes (panTro3); dog: C. familiaris (canFam2); bovine: B. taurus (bosTau6); opossum: M. domestica (monDom5); chicken: G. gallus (galGal3); lizard: A. carolinensis (anoCar2); frog: X. tropicalis (xenTro2); coelacanth: L. chalumnae (LatCha1); fugu: T. rubripes (fr3); medaka: O. latipes (oryLat2); zebrafish: D. rerio (danRer7).