{"id":346803,"date":"2023-03-29T05:00:00","date_gmt":"2023-03-29T12:00:00","guid":{"rendered":"https:\/\/reasons.org\/?p=346803"},"modified":"2023-03-29T05:00:00","modified_gmt":"2023-03-29T12:00:00","slug":"just-right-rna-structure-points-to-intentional-design","status":"publish","type":"post","link":"https:\/\/reasons.org\/creation\/life\/just-right-rna-structure-points-to-intentional-design","title":{"rendered":"Just-Right RNA Structure Points to Intentional Design"},"content":{"rendered":"\n

He is regarded as one of the best catchers to ever play major league baseball, and yet today Yogi Berra may be more well-known for his pithy and paradoxical statements, called \u201cYogi-isms,\u201d than his stellar baseball career. Berra\u2019s famous expressions have become part of our everyday lingo, so much so that I have interacted with a few younger people who have heard some of the more well-known Yogi-isms but had no idea who Yogi Berra was. <\/p>\n\n\n\n

Each Yogi-ism has a story that goes with it, offering some context for the quips. For example, when Yogi first said, \u201cwhen you come to a fork in the road, take it,\u201d he was giving his friend Joe Garagiola directions to his house in Montclair, NJ. Yogi lived on a cul-de-sac that went full circle. So, whether you went left or right at the fork you would wind up at his house.<\/p>\n\n\n\n

The story behind this Yogi-ism also applies to recent insight into the physicochemical forces that influence the secondary structure of RNA molecules. This new understanding reflects the work of a team headed by physicist Ard Louis from the University of Oxford.1<\/sup> As it turns out, their discovery reveals a deep-seated teleology (goal, purpose) to the structure and function of RNA molecules that evinces the intentional design of biochemical systems. <\/p>\n\n\n\n

Even when this newly discovered teleology to RNA secondary structure is viewed from within the evolutionary paradigm, the case for intentional design becomes inescapable. This work indicates that RNA secondary structures do not stem from the outworking of an unguided, historically contingent evolutionary process. To put it another way, either the secondary structures of RNA molecules have been directly designed or RNA secondary structures are the inevitable outcomes<\/em> of evolution. In this case, no matter what fork in the road evolution takes, it\u2019s going to wind up at the same spot every time, indicating a purpose and directionality to the evolutionary process.<\/p>\n\n\n\n

Before I describe this work and explore its philosophical and theological implications, a little background information would be helpful for some readers. For those who don\u2019t need a brief primer on RNA structure, feel free to skip to What Determines RNA Secondary and Tertiary Structure?<\/strong><\/p>\n\n\n\n

Levels of RNA Structure<\/strong>
RNA (ribonucleic acid) plays several important roles in the cell. It serves as an intermediary between DNA and proteins, transmitting the genetic information in DNA to the ribosome, where protein synthesis takes place. RNA molecules can also carry out specific functions on their own, such as catalyzing chemical reactions. In these instances, the RNA molecules are referred to as ribozymes.<\/p>\n\n\n\n

Closely related in structure to DNA, RNA is a single-stranded molecule composed of nucleotides, which consist of a nitrogen-containing base (called a nucleobase), a 5-carbon sugar (ribose), and a phosphate group. The nitrogen-containing bases in RNA are adenine (A), guanine (G), cytosine (C) and uracil (U). See figure 1.<\/p>\n\n\n\n

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Figure 1: Structure of RNA<\/strong>
Credit: Shutterstock <\/em><\/p>\n\n\n\n

There are three levels to RNA structure. The primary structure refers to the nucleotide sequence of the RNA strand. The secondary structure refers to the specific way the RNA strand interacts and folds upon itself. And the tertiary structure refers to the specific three-dimensional location in space of each atom of the RNA molecule.<\/p>\n\n\n\n

The three levels are nicely illustrated by transfer RNA (tRNA). This biomolecule plays a critical role in protein synthesis. It is relatively small, typically around 75\u201390 nucleotides in length (primary structure). The intrachain interactions create a characteristic clover leaf shape (secondary structure), which is composed of several structural elements: the acceptor stem, the anticodon loop, the D-loop, and the T\u03a8C loop. See figure 2.<\/p>\n\n\n\n

<\/p>\n\n\n\n

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Figure 2: Secondary Structure of RNA<\/strong>
Credit: Shutterstock<\/em><\/p>\n\n\n\n

The acceptor stem binds a specific amino acid. The anticodon loop contains the anticodon, a three-nucleotide sequence that base-pairs with a codon on the mRNA. The D-loop is a short stretch of RNA that is thought to stabilize the tRNA structure, while the T\u03a8C loop is involved in attaching the tRNA, charged with its amino acid, to the ribosome.<\/p>\n\n\n\n

The tRNA clover leaf folds into an L-shaped three-dimensional configuration. This specific shape allows the charged tRNA molecule to function as an adaptor molecule, carrying specific amino acids to the ribosome and aligning them with the codons on the mRNA so they can be assembled into a protein chain. See figure 3.<\/p>\n\n\n\n

<\/p>\n\n\n\n

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Figure 3: Tertiary Structure of RNA<\/strong>
Credit: Shutterstock<\/em><\/p>\n\n\n\n

What Determines RNA Secondary and Tertiary Structure?<\/strong>
RNA molecules found inside the cell adopt a wide range of secondary and tertiary structures. The research team hoped to gain insight that will help explain the basis for this varied RNA structure. <\/p>\n\n\n\n

One possibility: RNA structure can be accounted for by natural selection operating on the random variation of the RNA primary structures, in which the variation produces a vast number of secondary and tertiary structures, all with equal likelihood of occurring. An alternative possibility: RNA secondary and tertiary structures are determined by physicochemical forces, in which only certain<\/em> secondary and tertiary structures are possible. <\/p>\n\n\n\n

In the first scenario, natural selection dictates higher-order RNA structure. In the second scenario, the secondary and tertiary structures are constrained by the laws of nature. To simplify their work, Louis\u2019s team focused on RNA secondary structure (which is a determinant of RNA tertiary structure). They first interrogated the RNAcentral database, cataloging all known RNA secondary structures found in nature. <\/p>\n\n\n\n

They then compared the RNA secondary structures in nature with those generated from RNA molecules consisting of random nucleotide sequences for RNA chain lengths of 40, 55, 70, 85, 100, and 126 nucleotides, respectively. The researchers classified the folds into a set of abstract shapes.<\/p>\n\n\n\n

They did the same procedure for the RNA molecules contained in the RNAcentral database and discovered that the RNA molecules found in nature account for a small subset of all the possible shapes that principally could exist. The team estimated that somewhere between 103 <\/sup>to 106<\/sup> nucleotide sequences account for all the RNA shapes found in nature. For context, there are 1075<\/sup> possible sequences for an RNA molecule 126 nucleotides in length.<\/p>\n\n\n\n

The RNA shapes they recovered from the set of random RNA sequences were the same as those that occur for the RNA molecules found in nature. They also discovered that the frequency of the shapes generated from RNA molecules composed of random nucleotide sequences was the same frequency as the shapes of naturally occurring RNA molecules.<\/p>\n\n\n\n

In other words, the researchers discovered that a bias exists regarding RNA structure. Without the influence of natural selection, the shapes found in RNA molecules comprised of random nucleotide sequences are the same as those found in the RNAcentral database.<\/p>\n\n\n\n

That is to say, the shapes of RNA molecules have been presculpted. The shapes of naturally occurring RNA molecules are not<\/em> the outworking of an unguided historically contingent evolutionary process. Nor <\/em>have they been shaped by natural selection. The limited number of RNA shapes that occur in nature reflect physicochemical constraints.<\/p>\n\n\n\n

From an evolutionary perspective, if natural selection plays any type of role, it is to fine-tune nucleotide sequences of RNA for a specific function, but it operates on shapes that have been prescribed by the laws of nature as innately existing forms.<\/p>\n\n\n\n

Origin and Design of Hammerhead Ribozyme<\/strong>
Louis\u2019s team\u2019s discovery finds corroboration in an earlier study published in 2001 by Nobel Laureate Jack Szostak and a colleague.2<\/sup> These two investigators were trying to understand the origin and design (from within the evolutionary paradigm) of an RNA molecule called the hammerhead ribozyme. (This biomolecule catalyzes reversible RNA cleavage and RNA ligation reactions.) The shape of this ribozyme molecule\u2014the motif\u2014occurs widely in organisms across all domains and kingdoms of life. Based on its distribution among organisms, it appears as if the hammerhead ribozyme arose independently, multiple times. <\/p>\n\n\n\n

Using in vitro<\/em> selection experiments, the two researchers screened RNA molecules with random, unbiased nucleotide sequences with the capacity for self-cleavage. They discovered that those RNA molecules with the capacity for self-cleavage had the hammerhead ribozyme motif, even though their nucleotide sequence varied. They conclude: \u201cOur results suggest that the evolutionary process may have been channelled, in nature as in the laboratory, towards repeated selection of the simplest solution to a biochemical problem. . . . purely chemical constraints (that is, the ability of only certain sequences to carry out particular functions) can lead to the repeated evolution of the same macromolecular structures.\u201d3<\/sup><\/p>\n\n\n\n

RNA Molecules: Fit for a Purpose<\/strong>
This understanding of RNA secondary structure developed by Ard Louis and his collaborators adds support for the biochemical anthropic principle and, with it, the intentional design of biochemical systems. In my book\u00a0Fit for a Purpose<\/em> I make the case that, just like the constants of physics, the core biochemical systems are finely tuned. One implication of this fine-tuning is that biochemical systems\u2014the foundational systems of life\u2014are the product of a Mind.<\/p>\n\n\n\n

In my book, I present three criteria that must be satisfied for the anthropic principle to extend to biochemical systems:<\/p>\n\n\n\n