Abstract
Multiple lines of evidence support the hypothesis that the early evolution of life was dominated by RNA, which can both transfer information from generation to generation through replication directed by base-pairing, and carry out biochemical activities by folding into functional structures. To understand how life emerged from prebiotic chemistry we must therefore explain the steps that led to the emergence of the RNA world, and in particular, the synthesis of RNA. The generation of pools of highly pure ribonucleotides on the early Earth seems unlikely, but the presence of alternative nucleotides would support the assembly of nucleic acid polymers containing nonheritable backbone heterogeneity. We suggest that homogeneous monomers might not have been necessary if populations of heterogeneous nucleic acid molecules could evolve reproducible function. For such evolution to be possible, function would have to be maintained despite the repeated scrambling of backbone chemistry from generation to generation. We havetested this possibility in a simplified model system, by using a T7 RNA polymerase variant capable of transcribing nucleic acids that contain an approximately 1∶1 mixture of deoxy- and ribonucleotides. We readily isolated nucleotide-binding aptamers by utilizing an in vitro selection process that shuffles the order of deoxy- andribonucleotides in each round. We describe two such RNA/DNA mosaic nucleic acid aptamers that specifically bind ATP and GTP, respectively. We conclude that nonheritable variations in nucleicacid backbone structure may not have posed an insurmountable barrier to the emergence of functionality in early nucleic acids.

We suggest several different ways in which functional nucleic acids with heterogeneous backbones [mosaic nucleic acids (MNA)] (23) could evolve through repeated cycles of replication and selection. Some folded structures may simply be unaffected by a particular type of chemical heterogeneity, and thus might form equally well whether made of one polymer, or a second polymer, or a mosaic of the two. Alternatively, a backbone functional group from one polymer might be required at only one or a few specific positions in the folded structure, in which case a significant fraction of backbone-scrambled progeny would retain activity. More interesting is the possibility that functional groups from one polymer would be required at one or more positions, whereas different functional groups from the second polymer would be required at other specific positions. In this case, neither polymer alone could access the functional structure, but a fraction of mosaic transcripts could be functional. To test the idea that functional structures could evolve from mosaic nucleic acids, despite the presence of nonheritable variation in the sugar-phosphate backbone, we undertook the selection of RNA/DNA mosaic aptamers that recognize nucleotide ligands. We found that ATP- and GTP-binding aptamers emerged from mosaic libraries as easily as from homogeneous RNA or DNA libraries, although the aptamers resulting from the mosaic selections exhibited weaker ligand affinity.

Discussion
We have identified two MNA nucleotide-binding aptamers by in vitro selection. Each selection round placed selective pressure for functional binding on MNA, which contained a mixed, nearly equivalent fraction of deoxyribose or ribose sugars in the sugarphosphate backbone. As a consequence, binders that were dependent on fixed sugar arrangements were strongly selected against. Under these conditions, aptamer sequences that retain function despite variations in most or all sugar positions were retrieved. We conclude that, far from representing an evolutionary deadend, MNA could have provided a valuable source of heritable functionality for early organisms...

... We show that MNA aptamer sequences retain function despite the substitution of many, or all positions for deoxy- or ribonucleotides (Fig. 3B, Fig. 4B, Table 1). Other studies have indicated that similar or identical DNA and RNA sequences can share a common function. For example, in vitro selection studies have identified a DNA aptamer sequence that binds heme and retains some activity when synthesized as RNA (38). Similarly, DNA ver sions of some in vitro-selected RNA aptamers retain binding activity toward their targets (39). Additionally, a ribozyme ligase sequence was evolved into an active deoxyribozyme by only a few mutations (40). Finally, classical studies of various DNA-RNA chNA versions of the hammerhead ribozyme have demonstrated that some DNA substitutions can increase (41) or decrease activity (42). These results lend experimental support to genetic transfer hypotheses (43, 44). We suggest that MNA might facilitate such genetic transitions, e.g., as RNA-based cells evolved the ability to make DNA, they may have needed to tolerate the incorporation of deoxynucleotides into functional RNA molecules...

DanDare wrote:Oooh, this conversation goes in my goody bag. As soon as one sound abiogenesis pathway is finally demonstrated, finding out which one actually led to the present day is not as important and may never be known. Ive been keeping an eye on Szostak's work for a while now. Its great.

DanDare wrote:Oooh, this conversation goes in my goody bag. As soon as one sound abiogenesis pathway is finally demonstrated, finding out which one actually led to the present day is not as important and may never be known. Ive been keeping an eye on Szostak's work for a while now. Its great.

Animavore wrote:It's C all the way down

Rumraket wrote:

DanDare wrote:Oooh, this conversation goes in my goody bag. As soon as one sound abiogenesis pathway is finally demonstrated, finding out which one actually led to the present day is not as important and may never be known. Ive been keeping an eye on Szostak's work for a while now. Its great.

Then I'd recommend this page : http://genetics.mgh.harvard.edu/szostakweb/publications.html