Do Natural Aptamers Exist

Over the last 15 years, as the biochemical qualities of aptamers have been appreciated more, various scientists began to find natural aptamers in extant creatures, as had been predicted (Gold et al., 1997, 2002). We thought natural aptamers would be found if one looked properly, and those thoughts diminish in no way the stunning discoveries from Ron Breaker's laboratory (Mandal and Breaker, 2004; Mandal et al., 2004; Serganov et al., 2004); predictions are easy, and discovery is very hard work! Through careful genome scanning of many bacterial species, Breaker and his colleagues were able to identify conserved RNA structures that suggested "natural aptamers" and to then show that the predicted aptamers were signaling metabolite concentrations and driving an appropriate physiological response to those metabolic demands.

"Breakerism" must exist in mammals and other eukaryotes also but the sequence gazing that successfully identifies natural aptamers in the eubacteria is more difficult in eukaryotes (as Breaker has himself suggested (personal communication), and see Sudarsan et al., 2003); we simply do not have enough whole genome sequences of mammals to infer conserved RNA structures that play a regulatory role.

I continue to believe that mammalian organisms and genomes are messy, similar to Rube Goldberg machines. The perfectly trimmed mammalian genome might evolve after more planetary time, as probably exemplified by many eubac-terial and bacteriophage genomes. Genomes today reflect the confluence of evolutionary pressures and time, and 5 billion years on the earth is not really a long time (given replication rates for mammals).

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