Evolution of RNA editing in trypanosome mitochondria

Evolution of RNA editing in trypanosome mitochondria

^*Howard Hughes Medical Institute and ^†Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; ^¶School of Biological Sciences, Manchester University, Manchester, United Kingdom M13 9PT; ^§Laboratory of Protein Crystallography and Structural Biology, Physics Institute of Sao Carlos, University of Sao Paulo, Av. Dr. Carlos Botelho 1465, PO Box 369, Sao Carlos, SP, Brazil 13560-970; and ^**Department of Biology, University of California, 3401 Watkins Drive, Riverside, CA 92521

Abstract

Two different RNA editing systems have been described in the kinetoplast-mitochondrion of trypanosomatid protists. The first involves the precise insertion and deletion of U residues mostly within the coding regions of maxicircle-encoded mRNAs to produce open reading frames. This editing is mediated by short overlapping complementary guide RNAs encoded in both the maxicircle and the minicircle molecules and involves a series of enzymatic cleavage-ligation steps. The second editing system is a C₃₄ to U₃₄ modification in the anticodon of the imported tRNA^Trp, thereby permitting the decoding of the UGA stop codon as tryptophan. U-insertion editing probably originated in an ancestor of the kinetoplastid lineage and appears to have evolved in some cases by the replacement of the original pan-edited cryptogene with a partially edited cDNA. The driving force for the evolutionary fixation of these retroposition events was postulated to be the stochastic loss of entire minicircle sequence classes and their encoded guide RNAs upon segregation of the single kinetoplast DNA network into daughter cells at cell division. A large plasticity in the relative abundance of minicircle sequence classes has been observed during cell culture in the laboratory. Computer simulations provide theoretical evidence for this plasticity if a random distribution and segregation model of minicircles is assumed. The possible evolutionary relationship of the C to U and U-insertion editing systems is discussed.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Howard Hughes Medical Institute-University of California, 6708 MRL, 675 Charles Young Drive South, Los Angeles, CA 90095. E-mail: Simpson{at}hhmi.ucla.edu.
↵ ‖ Present address: Department of Mathematics, Heriot-Watt University, Edinburgh, EH14 4AS, United Kingdom.
This paper was presented at the National Academy of Sciences colloquium “Variation and Evolution in Plants and Microorganisms: Toward a New Synthesis 50 Years After Stebbins,” held January 27–29, 2000, at the Arnold and Mabel Beckman Center in Irvine, CA.
Abbreviations:

gRNA,

guide RNA;

kDNA,

kinetoplast DNA