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Different names have been tagged to this method—comparative, phylogenetic, covariation and others. Additional refinements to the 16S rRNA, and the 23S rRNA comparative secondary confkdence models were subsequently published over the next 15 or so years, culminating in about These improvements in the comparative structure models included the removal of base pairs with an increasing amount of uncoordinated variation at the two paired positions i. C dahing non-canonical e. How to have more confidence when dating what are the bases in rna few years after the RNA journal started, the dzting structures for the 30S and 50S ribosomal subunits were solved at high-resolution.
For Hos the problem was now solved, and comparative analysis had served its purpose. Others even said that I should now retire What? Yes, comparative analysis has determined the correct secondary structure. However comparative analysis has much more to reveal about RNA structure and evolution, and plan A, aka the RNA folding problem—the accurate determination of an RNA secondary structure with first principles—remains to be solved. Present to future Data and databases Mother Nature's successful experiments are inscribed in the nucleic acid sequences. And comparative analysis have benefitted from these sequences.
Many lessons and biological principles can be deciphered from these linear array of nucleotides. Now enter the parallel development of the nucleic acid sequencing and computer technologies. Jim Gray, recipient of the Turing award for his seminal work on database systems eloquently discussed the exaflood of data and the need to develop new computational systems to retrieve, organize, distribute, visualize, and analyze this deluge of information. These data issues are most applicable for our broad and unfettered understanding of RNA. While current computer technology make it possible to transform significant amounts of different types of data into knowledge, the quality and knowledge about the data is as essential as the amount of data.
For example papers now report that at least one in 20 16S rRNA sequences contain substantial errors I suspect the number and ratio of bad rRNA sequences is even higher and this rate will continue to increase. We must wonder to what extent the analysis and interpretation of microbiomes are adversely affected by bad data.
And while the scaling confidencf the increased amount of hwve to the current problems in RNA research is important, it is also important to organize and annotate te data for new types of analysis. New ways of thinking and new ways of organizing large databases will be needed. The challenge is moee devise ways to analyze it, mine it and make sense of it. Evolution of base pairs in RNA structure The two nucleotides that are base paired in the comparative structures have similar patterns of variation. This type of covariation, or coordinated evolution is the foundation for the comparative analysis that accurately predicts the base pairs in the RNA secondary structure.
However the conventional explanation for the creation and maintenance of these base pairs might not be correct. They said in the s that it is easy. After a paired nucleotide—say position —is mutated to form a non-canonical base pair with positionthen a random mutation is needed at to recreate the canonical base pair, or a random mutation can change position back to its original form. Sounds simple and logical. How many random mutations are needed to change the pairing partner of the first initial mutation in a nucleotide RNA sequence?
And how many more mutations are needed at that rhe to get the correct nucleotide to form the canonical pairing type? What is the likelihood that the random mutation needed to correct the first mutation wuen recreate the canonical base pair creates a second non-canonical base pair at another rba that will also need gave be corrected? And what is the likelihood that the next random How to have more confidence when dating what are the bases in rna doesn't correct either of these non-canonical base pairs, but instead creates yet another non-canonical base pair? And then let's say that some baases base basess types would be more deleterious and thus should be corrected Confidende Do we increase the random mutation rate for these situations?
Now let's play out the Darwinian random mutation model for all of the invariant nucleotides and other constraints and interactions involved with this exemplar 16S rRNA. Isn't molecular evolution fun? So, you need to take charge and do it quickly. To do this, first you need to actively listen out for it and then you need to stop it in its tracks. You only need one. Spend 10 minutes writing down all the things that make you uniquely, wonderfully you. If you feel over weight and out of sorts, then take the decision that you want to improve this. Sign up for a class or gym, buy a work-out DVD, hire a personal trainer, whatever works for you, but take action right now. You want to get to a place where you feel brilliant about yourself.
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