Supplementary Figure 9: Multiz multiple-sequence alignment of MMP21 orthologs.
From: MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates
An alignment of MMP21 orthologs from 100 vertebrate species, via the Multiz Alignments track in the UCSC Genome Browser (human hg19 assembly). Exons are numbered at the top. Several vertebrate clades are listed to the right. Clades in which MMP21 orthologs are absent or incompletely aligned are in red (cetartiodactyla, birds, reptiles). In combination with the ORF decay observed in the alignable portions of cetartiodactyl MMP21 sequences (Supplementary Fig. 10), this distribution is suggestive of convergent gene loss in these three clades. For the cetartiodactyl, bird and reptile species for which a genome assembly is available in the UCSC Genome Browser, we confirmed that the region aligned in Multiz fell within the MMP21 syntenic region, i.e., between EDRF1 and UROS. We also performed BLAST analysis (tblastn) at the NCBI server using the human MMP21 protein sequence and were unable to identify an MMP21 ortholog in birds and reptiles. Note that, although exon 1 for some fish and mammals is not aligned in Multiz, this appears more likely to be due to genome assembly gaps or functional sequence divergence rather than ORF decay.
