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insertional editing activity at the transcript level guided by the original G residue in the gRNA.

An alternative scenario for the origin of gRNAs can be derived from an analysis of computational algorithms for searching for possible gRNA genes that are complementary to candidate cryptogenes (Von Haeseler et al., 1992) in which it was shown that known gRNA sequences are in or very close to the statistical noise. Based on these results, one could speculate that the primordial gRNA was derived from some other mitochondrial RNA fragment that by chance base-paired with the mRNA downstream of the U-deletion site and contained a guiding A or G residue that could base-pair with an inserted U and thereby overcome this frameshift mutation and allow translation of the mRNA.

CONCLUSIONS

The mitochondrial genome of the kinetoplastid protists is a highly derived genome in which frameshift errors in the reading frames of 12 of the 18 genes are corrected at the RNA level by U-insertion/deletion editing, which probably arose in the early bodonid-kinetoplast lineage after divergence of the euglenoids. The sequence information for these corrections is partially located in a physically separate guide RNA genome. The most primitive type of organization of this genome may have been similar to that seen in the bodonids, B. saltans, B. caudatus, and C. helicis, in which the gRNA genes are present on multiple plasmid-like molecules. The next steps in evolution may have either been a concatenation of the plasmids into megacircles such as in T. borreli or a catenation of the plasmids into a network such as in the trypanosomatids.

The fact that daughter cells must receive a complete complement of all of the minicircle sequence classes encoding the gRNAs required for editing has led to the evolution of mechanisms for the random distribution of minicircles within the single network. The highly structured organization of the catenated minicircles within the network must have placed additional constraints on the evolution of this system. Two different types of mechanisms evolved, both based on a decatenation of minicircles from the network and replication at two antipodal nodes before recatenation of the daughter molecules. In the Leishmania-Crithidia clade (and T. cruzi), random selection of closed molecules and rotation of the network during the recatenation process in S phase produced a high degree of randomization. We have shown that computer simulations provide evidence that random segregation of minicircles during replication can account for many of the phenomena observed in L. tarentolae and possibly for the observed restriction of editing that has occurred in evolution. However, to explain the high abundance of unnecessary minicircle classes in the



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