Even though Amy wasn\u2019t all that enthusiastic about having her own mogwai, <\/em>it doesn’t change the enthusiasm that horror movie fans have for Gremlins<\/em>. The movie\u2019s plot begins to unfold when teenager Billy Peltzer receives a mogwai as a gift from his father. He had purchased the cute, furry, and sweet mogwai from an antique store in Chinatown. But Billy’s father was warned: <\/p>\n\n\n\n As expected, one of Billy\u2019s friends accidentally spills water on Gizmo and the creature spawns several more mogwai. These mogwai are much more mischievous than Gizmo and they trick Billy into feeding them after midnight. After they feed, they form cocoons and later emerge as reptilian creatures called gremlins. These newly spawned mogwai are led by the villainous Stripe, who escapes from the Peltzers’ home. Stripe jumps into the pool at the local YMCA, producing numerous gremlins who wreak havoc on the town.<\/p>\n\n\n\n This catastrophe all came about because, unbeknownst to Billy\u2019s father, mogwai exist in two forms, one cute and adorable and the other ugly and evil.<\/p>\n\n\n\n DNA’s Nucleobases Can Be Good or Bad<\/strong> A researcher from Trinity College in Dublin, Ireland, studied tautomerism in the nucleobases of DNA and discovered it could actually be worse.1<\/sup> As it turns out, the nucleobases’ composition in DNA is ideal. If DNA had been constructed with other nucleobases (conceivably available on early Earth), mutations caused by nucleobase tautomerism would have been more frequent, perhaps making life impossible.<\/p>\n\n\n\n This insight about tautomerism in the DNA nucleobases adds to scientists’ fundamental understanding of the structure of DNA. It answers an important \u201cwhy\u201d question; namely, why were adenine, guanine, and cytosine selected specifically to form DNA\u2019s structure? The answer also has philosophical and theological implications. DNA\u2019s structure displays a type of biochemical fine-tuning that reflects an exquisite molecular logic. Both indicate that DNA\u2019s structure must be the work of an intelligent Agent.<\/p>\n\n\n\n Before I unpack the researcher’s work and delve into the teleological implications, a brief primer on DNA\u2019s structure will be helpful. If you are familiar with the structure of DNA, feel free to skip ahead to Tautomers<\/strong>.<\/p>\n\n\n\n DNA\u2019s Structure<\/strong> <\/p>\n\n\n\n Figure 1: A Nucleotide<\/strong> The backbone of the DNA strand consists of alternating phosphate and deoxyribose moieties. This alternating back arises when the cell\u2019s machinery repeatedly links the phosphate group of one nucleotide to the deoxyribose unit of another nucleotide. The nucleobases extend as side chains from the backbone of the DNA molecule and serve as interaction points (like ladder rungs) when the two DNA strands align and twist to form the double helix (figure 2).<\/p>\n\n\n\n <\/p>\n\n\n\n Figure 2: The Structure of DNA<\/strong> When the two DNA strands align, the adenine (A) side chains of one strand always pair with thymine (T) side chains from the other strand. Likewise, the guanine (G) side chains from one DNA strand always pair with cytosine (C) side chains from the other strand.<\/p>\n\n\n\n When the side chains pair, they form crossbridges between the two DNA strands. The length of the A-T and G\u2013C cross bridges is nearly identical. Adenine and guanine are both composed of two rings and thymine (uracil) and cytosine are composed of one ring. Each crossbridge consists of three rings.<\/p>\n\n\n\n When A pairs with T, two hydrogen bonds mediate the interaction between these two nucleobases. Three hydrogen bonds accommodate the interaction between G and C. The specificity of the hydrogen bonding interactions accounts for the A-T and G-C base-pairing rules (figure 3).<\/p>\n\n\n\n <\/p>\n\n\n\n Figure 3: Base Pairing in DNA<\/strong> Tautomerism<\/strong> The most widely known example of tautomerism is called keto-enol tautomerization (figure 4).<\/p>\n\n\n\n <\/p>\n\n\n\n Figure 4: Keto-Enol Tautomerization<\/strong> If a compound is capable of tautomerization, it will spontaneously generate both tautomers (keto and enol) when dissolved in solution, if the solution conditions are right. For keto-enol tautomers, the keto form has much greater chemical stability and is the thermodynamically favored form. For this reason, in solution, the keto form will exist at a much higher concentration than the enol form. In addition to keto-enol tautomers, other tautomers exist such as the amide-imide tautomers, amine-imine tautomers and the lactam-lactim tautomers (figure 5).<\/p>\n\n\n\n <\/p>\n\n\n\n Figure 5: The Most Common Types of Tautomers<\/strong> Tautomerism and DNA<\/strong> Adenine and cytosine both interconvert between amino and imino forms (with the amino form analogous to the keto form and the imino form analogous to the enol form). The amino form predominates in both adenine and cytosine because it’s the more thermodynamically stable tautomer. <\/p>\n\n\n\n Guanine and thymine both interconvert between lactam and lactim forms (with the lactam form analogous to the keto form and the lactim form analogous to the enol form). The lactam form predominates in both guanine and thymine because it’s the more thermodynamically stable tautomer. <\/p>\n\n\n\n The consequences of nucleobase tautomerization aren\u2019t good. The hydrogen bonding interactions of the imino forms of adenine and cytosine and the lactim forms of guanine and thymine differ from the amino and lactam forms, respectively. These differences cause mispairing between the nucleobases of the two DNA strands, which can cause mutations during DNA replication.<\/p>\n\n\n\n DNA\u2019s chief function is storing the information needed to build the cell\u2019s components and the cellular machines that carry out vital processes within the cell. But tautomerism of DNA\u2019s nucleobases poses a threat to the integrity of the information housed in the nucleotide sequences of DNA because it causes mispairing that can lead to mutations, which compromise the integrity of the information stored in DNA. <\/p>\n\n\n\n DNA Is Optimized to Minimize Tautomerism\u2019s Harmful Effects <\/strong> As Mac D\u00f3naill points out, DNA would have been better suited to be built from more than<\/em> four nucleobases (and, hence, four nucleotide subunits). A larger set of nucleotide subunits would allow the information in DNA which specifies the complex functionality of the cell\u2019s machinery to be stored in shorter sequences.<\/p>\n\n\n\n So, did nature just simply stumble onto these four nucleobases as a consequence of an unguided, historically contingent evolutionary process? Was it prebiotic availability that influenced their selection? Or were there other reasons?<\/p>\n\n\n\n To answer these questions, Mac D\u00f3naill performed calculations using quantum mechanics to compare the stability of the tautomers of the nucleobases that naturally occur in DNA with the stability of tautomers of nonnatural nucleobases, such as isoguanine, isocytosine, and xanthine. He learned that the \u201cketo\u201d forms of adenine, guanine, cytosine, and thymine displayed greater stability (relative to the \u201cenol\u201d forms) compared to the tautomers of the nonnatural nucleobases he studied. The greater stability of the \u201cketo\u201d form of the nucleobases in DNA significantly minimizes the mispairing of nucleobases. If other nucleobases were selected for DNA, it would have been worse. This means that the nucleobases that make up DNA form what appears to be a uniquely optimal set that ensures the stability of DNA\u2019s information content by minimizing base mispairing that occurs because of tautomerism.<\/p>\n\n\n\n Other work (which I describe in The Cell\u2019s Design<\/a><\/em> and Fit for a Purpose<\/a><\/em>) indicates that the four nucleobases of DNA have other unique properties. For example, the adenine-thymine and guanine-cytosine pairs are the only ones that cause a distortion in the DNA double helix if misfiring of the bases occurs. <\/p>\n\n\n\n The four nucleobases also happen to be unique with respect to their photostability. Adenine, guanine, cytosine, and thymine withstand the damaging effects of UV radiation better than nonnatural nucleobases. In other words, the nucleobases found in DNA display multidimensional optimality, all of which ensure the integrity of the information housed within the DNA molecule’s structure.<\/p>\n\n\n\n DNA and the Case for Intentional Design<\/strong> For an engineer, optimization is synonymous with design. And optimized engineered systems don\u2019t just happen\u2014they result from engineers carefully fine-tuning their designs. Optimization requires forethought, planning, and careful attention to detail. DNA’s optimized structure constitutes evidence for the intelligent design of DNA. <\/p>\n\n\n\n DNA\u2019s Structure and Anthropic Coincidences<\/strong> The rationale and molecular logic that undergird the selection of the four nucleobases found in DNA make it unlikely that unguided, directionless, historically contingent evolutionary processes just stumbled upon the four nucleobases found in DNA. If this is the explanation for DNA\u2019s structure we would expect the nucleobase composition of DNA to have little rhyme or reason to it.<\/p>\n\n\n\n It’s also unlikely that natural selection is exclusively responsible for the choice of nucleobases found in DNA. This explanation would be plausible if the nucleobases in DNA were optimized for a single<\/em> feature. But the nucleobases in DNA are simultaneously optimized with respect to at least three<\/em> features. It’s remarkable\u2014and a bit eerie\u2014that the adenine-thymine and guanine-cytosine pairs appear to uniquely possess: (1) the just-right tautomeric stability, (2) the just-right photostability, and (3) the just-right tendency to distort the DNA double helix when mispairing of the nucleobases occurs. What are the odds? The simultaneity of these three just-right features for the nucleobases in DNA can\u2019t merely be a coincidence. There must be something more.<\/p>\n\n\n\n I would assert that the just-right properties of adenine, guanine, cytosine, and thymine that are critical to life point to a biochemical anthropic principle. That is, they appear to be prearranged by the laws of nature. The nucleobase composition of DNA appears to be prescribed by the laws of nature. These laws constrain the nucleobase composition (and the rest of DNA\u2019s structure). These constraints also happen to yield a set of nucleobases with the precise properties needed to ensure DNA is optimally suited for its role as an information storage molecule\u2014a critical property if life is to exist. And, as it turns out, this set of nucleobases appears to be uniquely suited for DNA.<\/p>\n\n\n\n That is to say, DNA appears to be uniquely fit for a purpose. And fitness for purpose is a hallmark of intentional design.<\/p>\n\n\n\n Thanks to its just-right nucleobase composition, DNA is less demanding than a mogwai. It can tolerate the light. It can get wet. And it will still have the structural integrity to spawn copies of itself. All by design.<\/p>\n\n\n\n Resources for Further Exploration<\/strong><\/p>\n\n\n\n The Optimal Structure of DNA<\/em><\/strong><\/p>\n\n\n\n DNA and the Anthropic Principle<\/em><\/strong><\/p>\n\n\n\n
Like mogwai, the nucleobases that contribute to the structure of DNA can also take on two forms, called tautomers. Biochemists are fully aware that one tautomer is beneficial, contributing to DNA’s structural integrity. The other form is harmful, triggering mutations in DNA during the replication process.<\/p>\n\n\n\n
DNA consists of two chain-like molecules (polynucleotides) that align and twist to form the DNA double helix. The cell\u2019s machinery generates polynucleotide chains by linking together four different subunit molecules called nucleotides. DNA is built from the nucleotides adenosine, guanosine, cytidine, and thymine, famously abbreviated A, G, C, and T, respectively. The nucleotide molecules that make up the strands of DNA are complex molecules (see figure 1), consisting of both a phosphate moiety, and a nucleobase (either adenine, guanine, cytosine, or thymine) joined to a 5-carbon sugar (deoxyribose). <\/p>\n\n\n\n![\"\"](\"https:\/\/reasons-prod.storage.googleapis.com\/wp-content\/uploads\/2022\/09\/shutterstock_741287659-1024x848.jpg\")
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Tautomers are organic compound pairs that mutually interconvert one into another through a special type of chemical reaction called tautomerization. The reaction involves a switch between adjacent single and double bonds accompanied by the formal migration of a hydrogen atom from an atom that takes part in the original single bond to an atom that takes part in the new single bond (which results from the single bond-double bond switch). <\/p>\n\n\n\n![\"\"](\"https:\/\/reasons-prod.storage.googleapis.com\/wp-content\/uploads\/2022\/09\/shutterstock_2147745063-1024x700.jpg\")
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The nucleobases found in DNA all undergo tautomerization reactions in solution. <\/p>\n\n\n\n
Because of the importance of nucleobases, D. A. Mac D\u00f3naill from Trinity College studied the tautomerism in DNA with an eye toward a larger question: Why were the four nucleobases adenine, guanine, cytosine, and thymine selected for DNA?<\/p>\n\n\n\n
In both The Cell\u2019s Design<\/em> and Fit for a Purpose<\/em>, I describe how all other aspects of DNA\u2019s compositional makeup and structural features are optimized for DNA’s role as an information storage molecular system, including the nucleobase composition and structure. This insight from Mac D\u00f3naill adds to the features of DNA\u2019s structure that are optimized. <\/p>\n\n\n\n
The case for intentional design goes beyond the optimized structure of DNA. The fine-tuning of DNA’s structure hints at a much deeper and richer teleology.<\/p>\n\n\n\n