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Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF
N Esumi1, M Budarf, L Ciccarelli
1Section on Molecular Structure and Function, National Eye Institute, Building 6 Room 331, National Institutes of Health, Bethesda, Maryland 20892-2740, USA.
Abstract:
Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are small proteins, which are related both by sequence and by in vitro enzyme activity. Here we show that the gene for DDT in human and mouse is identical in exon structure to MIF. Both genes have two introns that are located at equivalent positions, relative to a twofold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT. In addition to similarities in structure, the genes for DDT and MIF are closely linked on human Chromosome (Chr) 22 and mouse Chr 10.
Insights
Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) share similar gene structures and are located on the same chromosomes. This suggests a common evolutionary origin for these related proteins.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are functionally related small proteins.
- Previous studies indicated similarities in their amino acid sequences and in vitro enzymatic activities.
Purpose of the Study:
- To investigate the evolutionary and genomic relationship between MIF and DDT.
- To compare the exon-intron structures and chromosomal locations of the MIF and DDT genes in humans and mice.
Main Methods:
- Comparative gene structure analysis of human and mouse MIF and DDT genes.
- Identification and comparison of intron positions and phases relative to the open reading frame.
- Analysis of gene linkage and conservation across species.
Main Results:
- The human and mouse genes for DDT exhibit identical exon structure to the MIF gene.
- Both genes possess two introns at equivalent positions, suggesting a shared ancestral gene.
- Introns are located at similar positions but differ in phase relative to the open reading frame.
- Homologous genes with conserved intron positions were found in nematodes and plants.
- The MIF and DDT genes are located in close proximity on human Chromosome 22 and mouse Chromosome 10.
Conclusions:
- MIF and DDT likely evolved from a common ancestral gene, as evidenced by their conserved gene structure and organization.
- The findings provide insights into the evolutionary history and genomic regulation of the MIF/DDT superfamily.
- The close chromosomal linkage of MIF and DDT suggests coordinated regulation or shared functional roles.