The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms.
BACKGROUND
Runx genes encode proteins defined by the highly conserved Runt DNA-binding domain. Studies of Runx genes and proteins in model organisms indicate that they are key transcriptional regulators of animal development. However, little is known about Runx gene evolution.


RESULTS
A phylogenetically broad sampling of publicly available Runx gene sequences was collected. In addition to the published sequences from mouse, sea urchin, Drosophila melanogaster and Caenorhabditis elegans, we collected several previously uncharacterised Runx sequences from public genome sequence databases. Among deuterostomes, mouse and pufferfish each contain three Runx genes, while the tunicate Ciona intestinalis and the sea urchin Strongylocentrotus purpuratus were each found to have only one Runx gene. Among protostomes, C. elegans has a single Runx gene, while Anopheles gambiae has three and D. melanogaster has four, including two genes that have not been previously described. Comparative sequence analysis reveals two highly conserved introns, one within and one just downstream of the Runt domain. All vertebrate Runx genes utilize two alternative promoters.


CONCLUSIONS
In the current public sequence database, the Runt domain is found only in bilaterians, suggesting that it may be a metazoan invention. Bilaterians appear to ancestrally contain a single Runx gene, suggesting that the multiple Runx genes in vertebrates and insects arose by independent duplication events within those respective lineages. At least two introns were present in the primordial bilaterian Runx gene. Alternative promoter usage arose prior to the duplication events that gave rise to three Runx genes in vertebrates.
Rennert
Jessica
J
Stowers Institute for Medical Research, 1000 E, 50th Street, Kansas City, MO 64110, USA. jessrennert@msn.com
Coffman
James A
JA
Mushegian
Arcady R
AR
Robertson
Anthony J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D029941:Fish Proteins / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics*
D029742:Caenorhabditis elegans Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D029941:Fish Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; C493729:Runx3 protein, human; C493730:Runx3 protein, mouse; D014157:Transcription Factors