Monday, August 24, 2015

DNA SEQUENCE STABILITY

I have spent many years of my life dealing with the concept of deoxyribonucleic acid (DNA). My introduction to the wonders of that molecule happened around 1958. A French chemist discovered DNA in 1869. In 1958, while I still a student in physiological chemistry, a professor was lecturing to our class about cell chemistry, mentioned the relative abundance of nucleic acids in cells. He noted that in light of biological parsimony, that must mean they play a special part in cell chemistry. I cannot explain why that phrase stuck with me all these years, but it did, and it turns out to be the greatest understatement I have ever heard. I am in the process of writing book about the theory of evolution from the perspective of a physiological chemist. While editing a chapter dealing with the first appearance of DNA after the big bang, I was startled to realize the stability of that macromolecule is overwhelming. All chemists know that DNA is stable, so just that little bit of information was not new. What was new was an appreciation of how complex a macromolecule of DNA is and in light of that, how stable it is. There is no other macromolecule like it. Essentially, the sequence of nucleic acids in DNA is the same as it was the day the monomolecular building blocks first polymerized. Somewhere in the primordial environment, deoxyribonucleic acids first formed and randomly polymerized to form the macromolecules we recognize today. Of course, not the same building blocks but the same sequence. In my struggles to determine when that happened on the time scale of evolution, it fell somewhere over 3.5 to 4 million years ago. Some claim prokaryotes formed 3.6 million years ago. Scientists base their estimate on the best estimates of when the first forms of life appeared on earth, which means scientists assume the first DNA appears at the same time, which probably is, not be true, which is only one of the minor concepts I challenge in my book. The biggest challenge has to do with what I just mentioned about the first formation of DNA. It is common for biologists to suggest a plan of some sort embedded in DNA structure or to say something ridiculous like, “Deoxyribonucleic Acid is the blueprint for all inherited characteristics in living things.” This statement was taken from an educational web-site on the internet. How could a macromolecule randomly formed 3.5 million years ago design an organism? Pure nonsense. However, the objective of this post is to point out that a macro-polymer, that forms and reforms over the course of 3.5 to 4 millions years flawlessly maintain that original sequence. My understanding of this relates to the idea of self-healing. A sequence of deoxynucleotides randomly formed as the building block first deterministically formed. One of the characteristics of nucleotides is that they form phosphate bridges—again deterministically—with other nucleotides as well as hydrogen bonds with other nucleotides. DNA is composed of four nucleotides, adenine, cytosine, guanine, and thymine. Essentially these four different deoxyribonucleotides form phosphate bonds with each other to polymerize without preference ad infinitum except they form phosphate bridges only with other deoxyribonucleotides. Every sequence has a complementary sequence that is in reverse order and the base pairing depending on hydrogen bonding of A to T (two bonds) and C to G (three bonds), which is according to the classic A to T and C to G pattern. The term melting temperature or Tm refers the temperature above which the stands disassemble and reflects the relative number of bonds of each type. The usual body temperatures are invariable below that temperature. The background for this, when it happens, is essentially one of the scarcities of monomeric building blocks. In other words, as the building block are produced they become incorporated in the DNA sequence or pair with and existing polymer. Imagine a polymer and it co-polymer. The one that exist first will align newly formed monomeric units in an ordered sequence and position them to form the phosphate bridge. If an error occurs, and a mismatch happens, the phosphate bridge could not easily form “and” the hydrogen pair matching would fail until the mismatch deoxynucleotide could be deterministically removed and the proper matching co-sequence restored. The collective strength of the hydrogen bonds of all the properly matched deoxynucleotides hold the sequence and co-sequence in place while chemical forces remove the mismatched deoxynucleotide. Apparently, this is self-healing that has worked for 6 million of years. On a personalized basis, the DNA you received from your great grandfathers is identical to his. Of course, you have something like 12 sources from which to receive DNA. For the biologists, the challenge is to put this information into perspective in terms of all living things that share-surviving fragments of DNA from the time it first formed. It looks like my book dealing with this question will have about 400 pages if I ever get it written. URL: firetreepub.blogspot.com Comments Invited and not moderated

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