Abstract
BackgroundRunx 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.ResultsA 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.ConclusionsIn 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.
Highlights
Runx genes encode proteins defined by the highly conserved Runt DNA-binding domain
Runx genes encode the sequence-specific DNA binding subunit of a heterodimeric transcription factor, the defining feature of which is the Runt domain, a highly conserved 128 amino acid sequence involved in DNA binding, heterodimerization, nucleotide binding, and nuclear localization [1,2]
Undescribed Runx genes collected in our BLAST searches include two genes from the puffer fish (Takifugu rubripes) genome, a single gene from the sea squirt (Cionia intestinalis) genome, three genes from the mosquito (Anopheles gambiae) genome, and two new Runx genes from the fruit fly (Drosophila melanogaster)genome
Summary
Runx genes encode proteins defined by the highly conserved Runt DNA-binding domain. Runx genes encode the sequence-specific DNA binding subunit of a heterodimeric transcription factor, the defining feature of which is the Runt domain, a highly conserved 128 amino acid sequence involved in DNA binding, heterodimerization, nucleotide binding, and nuclear localization [1,2]. Runx genes have been discovered and functionally characterized in mammals, sea urchins and nematodes, and in general are involved in the transcriptional control of (page number not for citation purposes). Most studies of Runx gene function and regulation have been carried out in mammals and in D. melanogaster, each of which has multiple Runx genes It is not currently known how the Runx gene family evolved, nor is it known how many Runx genes the first animal possessed. Answering these questions will facilitate identification of primitive (general) and derived (specialized) aspects of Runx gene structure, function and regulation
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