HDV Family of Self-Cleaving Ribozymes - Progress in Molecular Biology and Translational Science - page 160

J1/2 insertion is common to retrotransposon-associated ribozymes, it likely
represents a gain-of-function mutation that is necessary for the ribozyme's
role in the retrotransposition cycle. If this is the case, the drz-Agam-2 family
could be the product of selective acquisition of a stable structure upstream of
a drz-Agam-1 ribozyme following a transposition event that brought a drz-
Agam-1 ribozyme and an ancestral retrotransposon into close proximity.
Such insertion would require the initial drz-Agam-1 5 0 P1 strand to be lost
through mutation or deletion and a new 5 0 P1 strand to take its place. It
seems plausible that such a sequence could appear by chance since the min-
imum length of the P1 helix in active ribozymes is only 6 bp.
The level of sequence variation observed between the HDV-like ribo-
zyme families can be explained in one of two ways. Either HDV-like
ribozymes arose very early and provided a function that was retained in sub-
sequent replication and speciation events, slowly accruing mutations that led
to the diversity one finds today, or the HDV ribozyme motif evolved inde-
pendently several times as a need arose in a given genome for a self-cleaving
RNA molecule.
The hypothesis that the observed HDV-like ribozyme diversity is the
product of a single, ancestral self-cleaving HDV RNA is backed by the fact
that HDV-like ribozymes have never been detected during in vitro selection
experiments for RNAs capable of self-scission. During these experiments,
the starting DNA pool can consist of 10 16 unique sequences. 142-144 This
is well beyond the sequence diversity found in any single genome, and
yet no HDV-like ribozymes have been isolated in vitro despite their wide-
spread occurrence in vivo . Based on the informational content of the HDV
motif, a starting pool of > 10 16 sequences would yield on average a single
HDV-like self-cleaving motif. Furthermore, the existence of less complex
RNA motifs capable of catalyzing the same self-scission reaction in vivo
would further decrease the chances of the HDV ribozyme motif evolving
independently on multiple occasions. Hammerhead ribozymes for instance,
which are found widely dispersed in nature, have also been isolated indepen-
dently several times in vitro . 5,6,110,142
Alternatively, several lines of evidence point to convergent evolution for
HDV-like ribozymes. It is unlikely that every instance of the motif evolved
independently as certain underlying features can be found among ribozymes
located in distantly related organisms. For instance, despite mutational data
showing that the J4/2 region can consist of the consensus sequence
“CNRA,” which has eight possible permutations, only five variants to this
region are observed in vivo . 3,42,4 If the motifs all evolved independently, all