Evolutionary implications of error amplification in the self-replicating and protein-synthesizing machinery

Evolutionary constraints operating on animal mitochondrial tRNA were estimated to be reduced to about 1/30 of those that apply to cytoplasmic tRNA. In the nuclear-cytoplasmic system, an effect of a mutation in tRNA is likely to be amplified through positive feedback loops consisting of DNA polymerases, RNA polymerases, ribosomal proteins, aminoacyl-tRNA synthetases, tRNA processing enzymes, and others. This amplification phenomenon is called an "error cascade" and the loops that cause it are called "error loops." The freedom of evolutionary change of cytoplasmic tRNA is expected to be severely restricted to avoid the error cascade. In fact, cytoplasmic tRNA is highly conserved during evolution. On the other hand, in the animal mitochondrial system, all of the proteins involved in error loops are coded for in the nuclear genome and imported from the cytoplasm, and accordingly the system is free from the error cascade. The difference in constraints operating on animal tRNA between cytoplasm and mitochondria is attributed to the presence or absence of error loops. It is shown that the constraints on mitochondrial tRNA in fungi are not as relaxed as those in animals. This observation is attributed to the presence of an error loop in fungal mitochondria, since at least one protein of the mitochondrial ribosome is coded for in the mitochondrial genome of fungi. The evolutionary rates of proteins involved in the processing of genetic information are discussed in relation to the error cascade.