HDV Family of Self-Cleaving Ribozymes - Progress in Molecular Biology and Translational Science - page 159

surrounding transcript and promote cap-independent translation initiation
of the message. The recent discovery of the R2 ribozymes and their pro-
posed roles in translation initiation make the possibility of the latter task
more likely, although the in vitro self-cleavage rate in physiological condi-
tions suggests that the majority of the transcripts would be cleaved on a time
scale too slow to promote expression of the protein. 2,3,140
6. EVOLUTIONARY RELATIONSHIP AMONG HDV-LIKE
RIBOZYMES
The widespread occurrence of HDV-like ribozymes raises questions
as to the origins of these motifs. Did the HDV ribozyme motif originate
in the distant past and remain relevant as genomes evolved, or are the many
examples of this motif a product of convergent evolution? The observed
variability among the Drosophila R2 ribozymes is consistent with a model
in which a single HDV-like ribozyme arose early in the evolutionary devel-
opment of the fruit fly and has been subjected to random mutations that
maintain the crucial catalytic requirements for self-scission. The rate of back-
ground mutations in Drosophila has been estimated to be around
11 mutations/kb every 1 million years, so for the observed approximately
50 mutations to occur between the most dissimilar R2 ribozymes, the
sequence would have had to originate over 25 million years ago. 141 Also,
R2 ribozymes have been postulated to spread vertically since no evidence
of horizontal gene transfer has been observed. 4,133
The evolutionary relationship between the R2 ribozymes and HDV-like
ribozymes in other organisms is more speculative. The HDV-like ribozymes
containing long inserts in the J1/2 region are largely associated with trans-
posable elements. It is therefore reasonable to assume that they share a com-
mon ancestral sequence that propagated via retrotransposition.
Whether these sequences are also evolutionarily related to HDV-like
ribozymes that do not contain extended J1/2 regions remains to be deter-
mined. Currently, only A . gambiae mosquitoes have been identified with
ribozymes containing both normal length and long J1/2 regions. Given
the high informational content of HDV-like ribozymes, it is unlikely that
the drz-Agam-1 and -2 families are examples of convergent evolution in
a single genome. However, 100 bp insertions specific to a nonessential
region of a functional RNA molecule are infrequent in occurrence, except
if there is some benefit in either having or not having the insertion. As the