Evolution of RNA editing in trypanosome mitochondria

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 C 34 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.

A High-OrderTrans-Membrane Structural Linkage Is Responsible for Mitochondrial Genome Positioning and Segregation by Flagellar Basal Bodies in Trypanosomes

“…Simpson et al, 2000;Cruz-Reyes et al, 2001;. T. brucei is characterized throughout its life cycle by the possession of a flagellum.…”

“…Maxicircles encode the mitochondrial proteins and some guide RNAs (gRNAs), whereas the minicircles are present in several thousand copies (1 kb in length), are heterogeneous in sequence, and encode gRNAs. The gRNAs are essential for the RNA editing process whereby the maxicircle encoded protein transcripts are modified by the addition or removal of uridine residues to produce the final mRNA molecules (Simpson and Maslov, 1999;Simpson et al, 2000;Cruz-Reyes et al, 2001;.…”

Guide RNAs of the recently isolated LEM125 strain of Leishmania tarentolae: An unexpected complexity

“…The presence of minicircle pairs with a similarity of over 90% encoding redundant gRNAs suggests an origin of the redundant gRNAs by duplication of ancestral minicircles followed by genetic drift within the variable region+ The existence of minicircles with a similarity of less than 60%, which is equivalent to that observed with minicircles encoding noncognate gRNAs, suggests that this process has been ongoing for a substantial period of time+ Loss of minicircles encoding redundant gRNAs could of course also be occurring, as predicted by computer simulations (Savill & Higgs, 1999;Simpson et al+, 2000) but the retention of at least one redundant gRNA for more than 30% of the editing blocks must be due to some selective pressure+ The 19 pairs of redundant gRNAs found probably represent a minimal number, as the total minicircle complexity of the genome has not yet been saturated in this study+…”

“…The minimal number of gRNAs required for productive editing of a pre-edited mRNA is determined by the number of editing blocks+ In the UC strain of L. tarentolae, there are 15 gRNAs encoded in the maxicircle DNA and a total of 17 gRNAs encoded in the approximately 10,000 catenated minicircle molecules that comprise the kinetoplast DNA network (Maslov & Simpson, 1992)+ The copy numbers of the different minicircle sequence classes exhibit a large variability and show a rapid rate of change in laboratory cultures (Simpson et al+, 2000)+ Five pan-edited cryptogenes in the UC strain that were labeled G1-G5 are not productively edited due to the absence of the required gRNAs, and the proteins are not expressed, indicating that these proteins are not required for life in culture (Thiemann et al+, 1994)+ However, transcripts of the homologous cryptogenes in the related species Trypanosoma brucei are productively edited in both stages of the biphasic life cycle, and the identified products include ND8, ND9, and ND3 (Read et al+, 1992(Read et al+, , 1994Souza et al+, 1992Souza et al+, , 1993Corell et al+, 1994)+ We showed previously that in the recently isolated LEM125 strain of L. tarentolae, the transcripts of these cryptogenes are also productively edited, which implies the presence of overlapping cascades of specific gRNAs in that strain (Thiemann et al+, 1994)+ In the initial work, 32 new gRNAs were identified from gRNA and minicircle DNA libraries, but it was estimated that at least 80 gRNAs would be required for the complete editing of these five cryptogene transcripts (Thiemann et al+, 1994)+ In this article, we have detected an additional 20 minicircle-encoded gRNAs that cover almost all the remaining blocks of editing in the transcripts of ND8, ND9, ND3, G4, and G5 from the LEM125 strain of L. tarentolae+ We have also discovered 18 pairs of redundant gRNAs, which are gRNAs of different sequences that could edit the same mRNA sequence block and are the result of the allowance of G:U as well as the canonical G:C base pairing in the gRNA:mRNA interaction+ No redundant gRNAs were previously seen in the UC strain (Maslov & Simpson, 1992) and only a single pair of redundant gRNAs was found in the initial study of the LEM125 strain (Thiemann et al+, 1994)+ The evolutionary implications of this evidence are discussed+…”

Evolutionary patterns of non-coding RNAs

“…Models for the evolution of the gRNA-based editing process are discussed in [223], a phylogenetic analysis of U-insertion editing [224] suggests that extensive editing is a primitive genetic phenomenon that has disappeared in more modern organism, see also [376].…”