Journal of Molecular Evolution

, Volume 63, Issue 5, pp 707–717

Evidence for an Early Gene Duplication Event in the Evolution of the Mitochondrial Transcription Factor B Family and Maintenance of rRNA Methyltransferase Activity in Human mtTFB1 and mtTFB2

Article

DOI: 10.1007/s00239-006-0075-1

Cite this article as:
Cotney, J. & Shadel, G.S. J Mol Evol (2006) 63: 707. doi:10.1007/s00239-006-0075-1

Abstract

Most metazoans have two nuclear genes encoding orthologues of the well-characterized Saccharomyces cerevisiae mitochondrial transcription factor B (sc-mtTFB). This class of transcription factors is homologous to the bacterial KsgA family of rRNA methyltransferases, which in Escherichia coli dimethylates adjacent adenine residues in a stem-loop of the 16S rRNA. This posttranscriptional modification is conserved in most metazoan cytoplasmic and mitochondrial rRNAs. Homo sapiens mitochondrial transcription factor B1 (h-mtTFB1) possesses this enzymatic activity, implicating it as a dual-function protein involved in mitochondrial transcription and translation. Here we demonstrate that h-mtTFB2 also has rRNA methyltransferase activity but is a less efficient enzyme than h-mtTFB1. In contrast, sc-mtTFB has no detectable rRNA methyltransferase activity, correlating with the lack of the corresponding modification in the mitochondrial rRNA of budding yeast. Based on these results, and reports that Drosophila melanogaster mtTFB1 and mtTFB2 do not have completely overlapping functions, we propose a model for human mtDNA regulation that takes into account h-mtTFB1 and h-mtTFB2 likely having partially redundant transcription factor and rRNA methyltransferase functions. Finally, phylogenetic analyses of this family of proteins strongly suggest that the presence of two mtTFB homologues in metazoans is the result of a gene duplication event that occurred early in eukaryotic evolution prior to the divergence of fungi and metazoans. This model suggests that, after the gene duplication event, differential selective pressures on the rRNA methyltransferase and transcription factor activities of mtTFB genes occurred, with extreme cases culminating in the loss of one of the paralogous genes in certain species.

Keywords

Mitochondria Transcription mtTFB TFB1M TFB2M MTF1 rRNA Methylation Gene Expression KsgA 

Supplementary material

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Supplementary material

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of PathologyYale University School of MedicineNew HavenUSA
  2. 2.Graduate Program in Genetics and Molecular BiologyEmory University School of MedicineAtlantaUSA