Intelligent Engineering of Life: A Journey into Gene Expression, Transcription, Translation, and Replication
Prologue
In my previous book, I embarked upon the exploration of the RNA-DNA nexus into the complex and intricate process of RNA and DNA biosynthesis. We saw how these molecules are assembled from simple building blocks, going through an amazingly complex biosynthesis process. Now, in this next, follow-up book, I will describe the process of gene expression and the intricate details of DNA transcription, translation, and replication. The flow of information between DNA, RNA, and proteins is one of the most fundamental principles of molecular biology. It is called the "central dogma of molecular biology" and it describes how the genetic information in DNA is used to create proteins. The flow of information between DNA, RNA, and proteins is a complex and dynamic process.
Now, we stand at the threshold, ready to unveil the secrets hidden within the core processes that have withstood the test of time, essential for life's continuity. We embark on a journey, drawing from the insights of both scientific discovery and philosophical inquiry. Our perspective delves beyond the realm of chance and necessity, embracing a paradigm that transcends the boundaries of conventional thought –including the perspective of intelligent design. Here, within the pages of this tome, we shall explore the intricate web of molecular interactions, the hidden cogs in the machinery of life. We shall unveil the enigmatic intricacies of gene expression, the process by which the genetic code is translated into observable traits and characteristics, giving life its remarkable diversity and adaptability. We shall witness the awe-inspiring intricacies of transcription, where DNA's message is transcribed into its RNA counterpart, the molecular intermediary that bridges the genetic code to the synthesis of proteins. We shall traverse the landscape of translation, the transformative process that breathes life into genetic information, crafting the very proteins that sculpt the essence of an organism's identity. Furthermore, we shall have a close look into the amazing phenomenon of DNA replication, the faithful duplication of life's code, ensuring the continuity of generations and the endurance of species throughout the eons. But beyond mere observation, we shall seek to understand the underlying purpose, the masterful design, that seems to infuse these processes with unparalleled efficiency and elegance. What unseen forces shaped the mechanisms that safeguard and perpetuate life across the millennia? As we move forth into this intellectual odyssey, we are not driven by a desire to refute or dismiss a priori any possible views, but rather, to embrace the confluence of scientific inquiry and plausible philosophical inferences that frame our worldview. Herein lies the crux of our pursuit – to explore the boundaries of knowledge, guided by the tenets of reason, open to both the rigors of empirical evidence and permit the inference to the most plausible explanation of origins. May this journey of knowledge and insight illuminate the path toward understanding the profound mysteries of life's awe-inspiring complexity.
Gene expression carried out through the gene regulatory network, transcription, translation, and DNA replication, are all life-essential and indispensable processes performed by all living cells. Their significance lies in their crucial roles in maintaining the integrity and functionality of the cell, orchestrating the synthesis of proteins, and propagating genetic information across generations. The gene regulatory network governs the activity of genes within a cell, controlling when and to what extent genes are expressed. This intricate network ensures that specific genes are turned on or off in response to various internal and external cues. Through this regulation, cells can respond to changing conditions and environmental stimuli, enabling them to adapt and function optimally. Proper gene regulation is essential for cell differentiation, development, and maintaining the appropriate balance of cellular activities. Transcription is the process by which genetic information encoded in DNA is copied into RNA. This step is critical because DNA cannot directly interact with cellular machinery for protein synthesis. By transcribing the genetic code into RNA, the cell creates a mobile and accessible messenger that can carry the genetic information to the cytoplasm, where translation takes place. Translation is the process by which the genetic information in RNA is decoded to synthesize proteins. Proteins are the workhorses of the cell, carrying out various functions that govern cell structure, metabolism, signaling, and defense. All cellular processes, from energy production to cell division, rely on the actions of specific proteins. Without translation, the cell would be unable to produce the essential proteins required for its survival and function. DNA replication is the process by which the cell duplicates its genetic material to ensure that each daughter cell receives a complete set of genetic instructions during cell division. Accurate and faithful DNA replication is crucial to maintaining the genetic integrity of the cell and passing on genetic information to future generations. Errors in DNA replication can lead to mutations, which may result in genetic diseases or disruptions in cellular function. These processes are universal in living cells, from simple single-celled organisms to complex multicellular organisms, demonstrating their fundamental importance for life as we know it. They form the core mechanisms of heredity, allowing organisms to pass on genetic information to their offspring and ensuring the continuity of life across generations.
DNA requires an intermediate step, transcription, to produce mRNA (messenger RNA) before it can be translated into proteins. This process is essential due to the fundamental differences between DNA and the cellular machinery responsible for protein synthesis, namely ribosomes. DNA is a double-stranded molecule composed of a long sequence of nucleotides. It is a stable molecule that serves as the genetic blueprint, carrying the instructions for building and maintaining an organism. The architecture of the DNA double-strand exhibits clear logic and purpose-oriented design. It is a fundamental feature that plays a crucial role in the stability, replication, and transmission of genetic information. There are several reasons why DNA is necessary to be double-stranded: DNA is composed of four types of nucleotides: adenine (A), thymine (T), cytosine (C), and guanine (G). The double-stranded structure allows the two DNA strands to interact through complementary base pairing. Adenine always pairs with thymine (A-T), and cytosine always pairs with guanine (C-G). This complementary base pairing ensures that the information on one strand is precisely replicated on the other during DNA replication, which is essential for maintaining the accuracy of genetic information. The double-stranded structure of DNA imparts stability to the molecule. The hydrogen bonds between the complementary base pairs (A-T and C-G) hold the two strands together, providing strength to the overall structure. This stability prevents the DNA molecule from easily breaking apart, ensuring the preservation of genetic information over generations. During cell division, when a cell replicates, the DNA must be accurately copied to ensure that the daughter cells receive an identical set of genetic information. The double-stranded nature allows the DNA to serve as a template for semi-conservative replication. Each of the two original DNA strands serves as a template for the synthesis of a new complementary strand, resulting in two identical daughter DNA molecules. The double-stranded structure also facilitates DNA repair mechanisms. When DNA is damaged, cells have sophisticated repair systems that can recognize and correct errors or mutations. Having two complementary strands allows the cell to use the undamaged strand as a template to guide the repair process and maintain the integrity of the genetic information. While DNA replication ensures the faithful transmission of genetic information, the double-stranded structure also provides opportunities for genetic variation through mechanisms like mutations and recombination. These variations are important for adaptation, allowing organisms to respond to changing environments and contributing to the diversity of life. DNA's double-stranded structure and its location in the cell nucleus (in eukaryotes) or the nucleoid region (in prokaryotes) make it inaccessible to the cellular machinery responsible for protein synthesis, which is found in the cytoplasm. Transcription is necessary because mRNA is a single-stranded molecule that can easily pass through the nuclear membrane (in eukaryotes) or directly be accessible in the cytoplasm (in prokaryotes). RNA polymerase enzymes recognize specific regions on the DNA called promoters and initiate the synthesis of complementary RNA strands (mRNA) based on the DNA template. Once the mRNA is synthesized, it can exit the nucleus (in eukaryotes) or be immediately available for translation (in prokaryotes). Translation is the process by which mRNA is decoded to produce proteins. It occurs in ribosomes, which are complex cellular structures made up of RNA and proteins. Ribosomes read the sequence of nucleotides on the mRNA in sets of three (codons) and match each codon to a specific amino acid carried by transfer RNA (tRNA). This process leads to the synthesis of a polypeptide chain, which then folds into a functional protein. In this exploration of the marvels of life's intricacies, we embark on a journey through the unimaginably complex biosynthetic and manufacturing steps that lead to the creation and precise delivery of proteins, the building blocks of cellular function. Each step involves a symphony of molecular machines and processes, orchestrated with exquisite precision, raising intriguing questions about the origin and design of life.
The Central Dogma of Molecular Biology
The "central dogma of molecular biology" outlines a remarkable flow of information, a series of orchestrated steps from DNA to RNA to protein. This fundamental process serves as the foundation of life for all pro- and eukaryotic organisms, with only a few exceptions, like the reverse transcription observed in retroviruses' RNA genomes. Genomic DNA stands as the storied blueprint for life, housing the building plans of living beings. Genes are the segments of DNA that can be transcribed into RNA, and this transcription is carried out by specialized enzymes known as RNA polymerases. These remarkable enzymes catalyze the DNA-dependent synthesis of RNA, each serving different functions in the cell. RNA polymerase I is responsible for transcribing the genes encoding the three rRNAs, the structural components of ribosomes. Meanwhile, RNA polymerase III specializes in producing small RNA molecules, such as 5S rRNA and various tRNAs, which are crucial for essential cellular functions. These genes, associated with these two RNA polymerases, are often referred to as "housekeeping genes" due to their ubiquitous expression and relatively straightforward regulation. In contrast, RNA polymerase II, known as Pol II, undertakes the task of transcribing all 20,000 protein-coding genes and most non-coding RNAs (ncRNAs). Unlike the housekeeping genes, Pol II-transcribed genes are tightly regulated and respond to various intra- and extracellular signals. The regulation of Pol II's activity involves an intricate interplay of numerous transcription factors and other nuclear proteins, which serve as key players in the finely tuned symphony of gene expression. The Transcription Start Site (TSS) marks the first nucleotide transcribed into mRNA, defining the gene's 5'-end or "start." Analogously, the 3'-end of a gene is where RNA polymerases dissociate from the DNA template. Intergenic regions, existing between genes, represent a significant portion of the genome, constituting about 85% of the human genome. Only about 15% of the genome is transcribed into pre-mRNA, from which mature mRNA molecules are formed through the process of splicing. Splicing, occurring during transcription, skillfully removes introns and joins exons, producing mature mRNA molecules. These mature mRNA molecules are protected from degradation by capping and polyadenylation processes at their 5'- and 3'-ends, respectively. Subsequently, the mature mRNA molecules embark on a journey from the nucleus to the cytoplasm, utilizing ATP in an active transport process. Once in the cytoplasm, the ribosomes scan the mRNA from its 5'-end, seeking the start codon AUG—the signal for the initiation of protein translation. The ribosomes then assemble and skillfully translate the mRNA's genetic code into a polypeptide chain until they reach one of three stop codons (UAA, UAG, or UGA). The regions upstream and downstream of the start and stop codons are referred to as the 5'-UTR and 3'-UTR, respectively. Throughout the process of transcription, various protein complexes gather along the mRNA, forming a mature messenger ribonucleoprotein (mRNP) that is eventually exported to the cytoplasm. While all steps of transcription are essential, the initiation step is particularly controlled and regulated to ensure precise gene expression. Nevertheless, the later steps of gene expression, including mechanisms that halt gene expression, are also of great significance. In this context, non-coding RNAs (ncRNAs) play crucial regulatory roles.
The "central dogma of molecular biology" serves as a guiding principle, delineating a clear path through which information flows from DNA to RNA and eventually to proteins. This elegant and remarkable process governs the construction of all pro- and eukaryotic organisms, with only a handful of exceptions, such as the reverse transcription seen in the RNA genome of retroviruses. Imagine DNA as a vast reservoir of blueprints, meticulously storing the architectural plans for all living beings. Like a master architect, it holds the keys to life's intricate structures and functions. As this genetic blueprint unfolds, it orchestrates a symphony of molecular interactions, leading to the production of RNA—the messenger that conveys vital instructions to the cellular workforce. The journey from DNA to RNA is both captivating and precise. DNA's double-helix structure unwinds, revealing the genetic code like a well-guarded secret. As the genetic message is transcribed into RNA, it's akin to transcribing notes from a hidden musical score. This transcriptional process is the foundation upon which life's music is composed. But the journey doesn't end there; it's merely the prelude to the grand performance. The RNA, now brimming with the essence of DNA's instructions, embarks on a mission to the cellular factory—the ribosome. There, like a skilled conductor guiding an orchestra, the ribosome reads the RNA's musical notes, known as codons, and directs the choreography of protein synthesis. The result is a harmonious dance of amino acids assembling into intricate protein structures—a dance that shapes life's functions. Though some organisms defy the conventional rules, the majority adhere faithfully to this wondrous system of genetic information transfer. Reverse transcription in retroviruses, for instance, adds an intriguing twist to the tale, as RNA takes a U-turn, transforming back into DNA before embedding itself into the host genome. The intelligent setup is evident throughout this mesmerizing process. DNA stores the master blueprint behind the awe-inspiring diversity of life. The designer, the unseen programmer, has patiently sculpted and fine-tuned each unique arrangement.
The flow of information from DNA to RNA to protein follows a well-orchestrated process, akin to a finely tuned performance. The gene, the fundamental unit of heredity, begins its journey with the Transcription Start Site (TSS) as its starting point. The TSS, though lacking a defined sequence, marks the initiation of transcription into mRNA—a critical step that kickstarts the gene's story. As the gene body is transcribed, a single-stranded pre-mRNA is crafted, consisting of numbered green and brown exons, intermingled with intervening introns (i). These introns may seem like extraneous interruptions, but they play a vital role in the gene's tale. Like a skilled editor perfecting a manuscript, the process of splicing meticulously removes the intervening introns, leaving behind a streamlined mRNA ready to be polished for its grand debut. The mRNA is protected from external threats by the addition of a nucleotide cap at its 5'-end and a tail of hundreds of adenines at its 3'-end—a process known as polyadenylation (ii). Having undergone these meticulous preparations, the mature mRNA is now ready for its grand journey from the nucleus to the cytoplasm. This voyage is no passive affair; it requires the energy-consuming efforts of an active process, as the mRNA traverses the nuclear pores (iii). Once in the cytoplasm, the mRNA reveals its coded secrets to the waiting ribosomes—small and large subunits eager to begin the mesmerizing dance of protein translation. Scanning the mRNA from its 5'-end, they search for the elusive "start codon" AUG, where the translation spectacle commences. Step by step, amino acids are assembled into polypeptide chains until they reach the sequence UAA, UAG, or UGA—the "stop codons" that bring the translation to a graceful conclusion (iv). However, not all parts of the mRNA contribute to this performance. The sequences upstream of the start codon and downstream of the stop codon remain untranslated, forming the 5'- and 3'-UTRs—silent bookends to the protein-coding region. As the final act in this molecular play, the resulting polypeptide chains undergo a metamorphic transformation. They fold into intricate three-dimensional structures, becoming proteins—tools of life essential for a myriad of functions. Many proteins also undergo post-translational modifications, refining their functional profile to fulfill specific roles (v). Throughout this odyssey, the central dogma of molecular biology holds true, guiding the one-directional flow of information from DNA to RNA to protein. The brilliance of this mechanism, an exemplar of intelligent design, is evident in the precision and finesse with which it orchestrates life's symphony without falter or confusion.
Messenger RNA is a central player
The profound genius lies in the exquisite control over which recipes are "cooked" from this DNA-book in different cells, creating a remarkable diversity of cell types and functions in our bodies. At the heart of this orchestration are four major stages, each dedicated to shaping the destiny of messenger RNA (mRNA) molecules, the intermediaries that carry the instructions from the DNA to the protein factories called ribosomes: The process of transcription allows the DNA to express its recipes by copying the gene sequences into mRNA molecules. These mRNA molecules, carefully transcribed according to the DNA sequence, contain the precise instructions for constructing a specific protein. This step is akin to a meticulous copyist, ensuring that the recipes are reproduced accurately. Once transcribed, the mRNA molecules are transferred from the cell nucleus, a safeguarding vault where the precious DNA-book resides, into the bustling cytoplasm. This intra-cellular environment outside the nucleus serves as the bustling kitchen where proteins are assembled. The mRNA never ventures far from its secure nucleus, safeguarding the integrity of the DNA-book. The heart of the protein factory lies within the ribosome, an exquisite machine that reads the instructions encoded in the mRNA and crafts the corresponding protein. The sequence of amino acids, dictated by the mRNA nucleotide sequence, determines the nature and functionality of the protein. As the ribosome's precision unfolds, the proteins emerge, each contributing to the diverse repertoire of cellular functions that define who we are. Like a well-tuned system, mRNAs are not left to linger indefinitely. Instead, they are carefully turned over and degraded by specialized factors. Remarkably, the same factors that partake in transcription also contribute to mRNA decay, seamlessly connecting these intertwined processes. The intricate web of gene regulation that governs mRNA synthesis, transport, translation, and decay showcases a level of foresight and intentionality that evokes awe. The fine-tuned coordination of these processes ensures the harmonious functioning of our cells, each with its unique role to play in the symphony of life. The precision with which genes are regulated, allowing for specific proteins to be expressed in particular cells, demonstrates a purposeful design that speaks of an intelligent agency behind the curtain of life's grand theater.
Interdependence in the central dogma of life
At the beginning of this production line of proteins lies the gene regulatory network, a master conductor that determines when and which gene should be expressed. This network acts as the decision-maker, directing the flow of genetic information and ensuring that the right proteins are produced at the right time and in the right quantities. With the baton in the hands of the gene regulatory network, RNA polymerase takes the stage, initiating the transcription process. It carefully reads the genetic code and synthesizes RNA molecules that serve as messengers to convey genetic instructions. The production of RNA is not without scrutiny. Core polymerase and transcription factors act as vigilant quality checkers, ensuring that errors are detected and corrected so that the accurate genetic message is preserved. As the RNA strands emerge, they undergo a series of artistic modifications, including capping and splicing. These alterations provide stability and ensure that only the relevant portions of the genetic code are used, adding layers of complexity to the production process. In the progress, elongation of the RNA strands takes place, leading to cleavage and polyadenylation. These additional processes are critical for the final composition of the RNA and contribute to the precision of protein synthesis. Next, the ribosome takes center stage, where the choreography of initiation, completion, and protein folding unfolds. Each step is executed with grace and accuracy, showcasing the intricacy of the translation process. But the production of proteins is only part of the masterpiece. Protein targeting mechanisms ensure that each protein finds its way to the right cellular compartment, akin to a dancer finding their place on stage. No production is complete without quality control. Ribosome quality control and various checkpoints meticulously inspect the proteins, rejecting any flawed performances and preserving the integrity of cellular function. The production line continues with posttranslational processing in eukaryotic cells, where proteins undergo a series of modifications in the endoplasmic reticulum. Transmembrane and water-soluble proteins receive their final touches through glycosylation, further enhancing their functionality. At every step of this awe-inspiring journey, we witness the delicate interplay of molecular machines, each composed of numerous subunits and co-factors, working harmoniously to create and deliver proteins with remarkable precision. The complexity and interdependence of these processes present a challenge to the notion of unguided origins. Instead, they evoke a compelling case for intelligent design—a purposeful process crafted with extraordinary foresight.
The remarkable complexity and interdependence of the biological production line for protein synthesis pose an unbridgeable challenge to the idea of unguided origins. The intricate orchestration of numerous molecular machines and processes, each with specific functions and interactions, suggests a level of sophistication that goes beyond what could reasonably be expected from random, unguided mechanisms.
Each step in the production line serves a specific purpose and contributes to the accurate synthesis and delivery of proteins. The genetic code, stored in DNA and transferred through RNA, is a highly specific and information-rich language. Information theory suggests that the origin of complex information, like the genetic code, is most plausibly attributed to an intelligent source capable of encoding meaningful instructions. The production line's irreducible complexity refers to the idea that removing or altering any step would disrupt the entire process, rendering it non-functional. The system could not have self-assembled gradually through unguided events, as intermediate stages would lack functionality. The seamless coordination of molecular machines and processes implies a level of integrated design. For this complex production line to work effectively, all components must be in place and functioning together from the outset. Many of the steps in the production line, such as RNA splicing and protein folding, are tightly regulated and precisely controlled. The presence of intricate quality control mechanisms implies a purposeful design to ensure the proper functioning of the system. The ability of proteins to be targeted to specific cellular compartments further demonstrates the precision and foresight involved in the production process. This targeted delivery is crucial for the proper functioning of complex cellular structures. The production line's emergence would require the simultaneous appearance of multiple interdependent components, each with specific functions. The probability of these components arising together through unguided processes is exceedingly low, making intelligent design a more plausible explanation. To date, there is no comprehensive naturalistic explanation for the simultaneous emergence of the many complex processes and molecular machines involved in protein synthesis. The explanatory power of intelligent design arises from its ability to account for the specified complexity and interdependence observed in living systems.
An example of how science communicators of mainstream media rely on guesswork to explain the origin of these complex systems can be seen in the article from Peter Dockrill: Scientists May Have Discovered The Shape of The Very First Proteins That Started Life, published on 20 March 2020. 1 In the article, Dockrill attempts to explore the possible shape and configuration of the earliest building blocks of life, dating back billions of years. The study uses computer modeling to simulate the molecular arrangements of ancient proteins that no longer exist on Earth. The research seeks to shed light on life's origins. Throughout the article, Dockrill uses words like "could be," "might best fit," "hypothesize," and "think." This kind of language reflects the speculative nature of the research and the limitations of the approach. These are theories and hypotheses, not definitive conclusions. The study's findings are based on the comparison of existing 3D protein structures to infer a common ancestor. However, the lack of direct evidence from fossils or ancient protein samples makes it challenging to confidently determine the exact shape and structure of ancient proteins. Dockrill suggests that life's origins might have started with "small, simple peptides" that extracted energy from the environment. There is an immense complexity involved in the transition from non-living matter to the first living organisms. The formation of functional proteins and the emergence of cellular processes involve numerous intricate steps. The article mentions the potential detection of life on other planetary bodies based on abiotic chemistry and biosignatures. While this is an exciting area of astrobiology research, it is vital to differentiate between the existence of life and the potential for life to arise in specific environments. Conflating the two could lead to misconceptions about the nature of life's origin. The use of computer modeling in scientific research is valuable, but it also has limitations. Modeling is a tool for generating hypotheses and exploring possibilities, but it cannot provide definitive evidence without experimental validation.
Already in 1958, Francis Crick recognized the problem of the interdependence of the various molecular machine complexes required to synthesize proteins. He wrote:
The basic dilemma of protein synthesis ha8 been realized by many people, but it has been particularly aptly expressed by Dr A. L. Dounce (1956); My interest in templates, and the conviction of their necessity, originated from a question asked me on my Ph.D. oral examination by Professor J. B. Sumner. He enquired how I thought proteins might be synthesized. I gave what seemed the obvious answer, namely, that enzymes must be responsible. Professor Sumner then asked me the chemical nature of enzymes, and when I answered .that enzymes were proteins or contained proteins as essential components, he asked whether these enzyme proteins were synthesized by other enzymes and so on ad Infinitum. The dilemma remained in my mind, causing me to look for possible solutions that would be acceptable, at least from the standpoint of logic. The dilemma, of course, involves the specificity of the protein molecule, which doubtless depends to a considerable degree on the sequence of amino acids in the peptide chains of the protein. The problem is to find a reasonably simple mechanism that could account for specific sequences without demanding the presence of an ever-increasing number of new specific enzymes for the synthesis of each new protein molecule. It is thus clear that the synthesis of proteins must be radically different from the synthesis of polysaccharides, lipids, co-enzymes and other small molecules; that it must be relatively simple, and to a considerable extent uniform throughout Nature; that it must be highly specific, making few mistakes; and that in all probability it must be controlled at not too many removes by the genetic material of the organism. 2
Francis Crick's writings from 1958 demonstrate his early recognition of the problem of interdependence in protein synthesis. He grappled with the challenges posed by the specificity of the protein molecule and the need for a mechanism that could account for specific sequences without an infinite regression of enzymes. Crick acknowledged that the dilemma of protein synthesis had been realized by many people, and he referred to Dr. A. L. Dounce's expression of this dilemma in 1956. The central issue is how proteins, with their high specificity, are synthesized without requiring an ever-increasing number of new specific enzymes for each new protein molecule. Crick's Ph.D. oral examination with Professor J. B. Sumner led to a realization that enzymes, responsible for protein synthesis, were themselves proteins or contained proteins as essential components. This raised the question of whether these enzyme proteins were synthesized by other enzymes, potentially leading to an infinite regress of enzyme synthesis. Crick highlighted that the specificity of the protein molecule depends considerably on the sequence of amino acids in the peptide chains of the protein. This specificity is essential for their biological function and adds to the challenge of explaining their origin and synthesis. Crick emphasized the necessity of finding a reasonably simple mechanism that could account for specific sequences without requiring an excessive number of specific enzymes. This indicates his early understanding of the concept of irreducible complexity, wherein certain biological systems require all their components to be present and functional simultaneously. Crick speculated that protein synthesis must be controlled by the genetic material of the organism, suggesting the involvement of DNA and RNA in directing the synthesis of proteins. This foreshadows the central dogma of molecular biology, which elucidates the flow of genetic information in cells. Crick's writings from 1958 clearly demonstrate his early awareness of the interdependence and complexity involved in protein synthesis. He recognized the challenges posed by the specificity of proteins and the need for a mechanism that could account for their specific sequences without an infinite number of enzymes. Crick's insights laid the groundwork for further research in molecular biology and inspired ongoing investigations into the origins of life's complexity.
The astonishing complexity of biosyntheses and production-line-like manufacturing processes in living organisms is nothing short of a marvel. Each of these intricate steps demands an elaborate orchestra of molecular machines, intricately composed of numerous subunits and co-factors, working in perfect harmony to accomplish their tasks. These molecular machines are truly masterpieces of design, carefully crafted to carry out their functions with precision. Yet, the origin of such elaborate molecular machinery poses an enigmatic challenge—an irreducible catch-22 problem. Imagine a series of at least 25 unimaginably complex biosynthesis steps, each requiring specialized molecular machinery. These steps are akin to a manufacturing assembly line, where raw materials are transformed into exquisite end products. At the core of these processes are molecular machines, composed of intricate arrangements of subunits and co-factors, with each component playing a specific role. These machines work with unparalleled efficiency, manufacturing essential molecules, proteins, and structures that drive life's intricacies. The catch-22 arises from the interdependence of these molecular machines. Each machine requires specific subunits and co-factors to function effectively, yet these components themselves need prior processing and assembly to become fully operational. This intricate web of dependencies forms a complex puzzle—an irreducible challenge that seems impossible to solve without all the pieces in place. This catch-22 problem is like a chicken-and-egg scenario, where the existence of one component depends on another, and vice versa. One might wonder: how could these complex molecular machines come into existence without all the necessary components already assembled?
Following are the processes employed by the cell to produce proteins:
- the gene regulatory network "selects" when which gene is to be expressed
- initiation of transcription by RNA polymerase
- transcription error checking by core polymerase and transcription factors
- RNA capping
- elongation
- splicing
- cleavage
- polyadenylation and termination
- export from the nucleus to the cytosol
- initiation of protein synthesis (translation) in the ribosome
- completion of protein synthesis
- protein folding
- maturation
- ribosome quality control
- protein targeting to the right cellular compartment
- engaging the targeting machinery by the protein signal sequence
- call cargo proteins to load/unload the proteins to be transported
- assembly/disassembly of the translocation machinery
- various checkpoints for quality control and rejection of incorrect cargos
- translocation to the endoplasmic reticulum
- posttranslational process of proteins in the endoplasmic reticulum of transmembrane proteins and water-soluble proteins
- glycosylation of membrane proteins in the ER (endoplasmic reticulum)
- addition of oligosaccharides
- incorrectly folded proteins are exported from the ER, and degraded in the cytosol
- transport of the protein cargo to the end destinations and assembly
In order for evolution to start, this robot-like working machinery and assembly line must be in place, and fully operational. The origin of these machines cannot be explained through evolution. All it is left, are random chemical reactions, or intelligent design.
1. F
2. F -> A & B & C & D & E
3. A & B & C & D & E -> requires Intelligence
4. Therefore Intelligence
A: The RNA and DNA molecules
B: A set of 20 amino acids
C: Information, Biosemiotics ( instructional complex mRNA codon sequences transcribed from DNA )
D: Transcription and translation mechanism ( adapter, key, or process of some kind to exist prior to translation = ribosome )
E: Genetic Code
F: Functional proteins
1. Life depends on proteins (molecular machines) (D). Their function depends on the correct arrangement of a specified complex sequence of amino acids.
2. That depends on the existence of a specified set of RNAs and DNAs (A), amino acids (B), transcription through the RNA polymerase (D), and translation of genetic information (C) through the ribosome (D) and the genetic code (E), which assigns 61 codons and 3 start/stop codons to 20 amino acids
3. Instructional complex Information ( Biosemiotics: Semantics, Synthax, and pragmatics (C)) is only generated by intelligent beings with foresight. Only intelligence with foresight can conceptualize and instantiate complex machines with specific purposes, like translation using adapter keys (ribosome, tRNA, aminoacyl tRNA synthetases (D)) All codes require arbitrary values being assigned and determined by an agency to represent something else (genetic code (E)).
4. Therefore, Proteins being the product of semiotics/algorithmic information including transcription through RNA polymerase and translation through the ribosome and the genetic code, and the manufacturing system ( information directing manufacturing ) are most probably the product of a super powerful intelligent designer.
The problem of getting functional proteins is manyfold. Here are a few of them:
A) The problem of the prebiotic origin of the RNA and DNA molecule
1. DNA ( Deoxyribonucleotides) are one of the four fundamental macromolecules used in every single cell, in all life forms, and in viruses
2. DNA is composed of the base, ribose ( the backbone), and phosphorus. A complex web of minimally over 400 enzymes are required to make the basic building blocks, including RNA and DNA, in the cell. This machinery was not extant prebiotically.
RNA and DNA is required to make the enzymes, that are involved in synthesizing RNA and DNA. But these very enzymes are required to make RNA and DNA? This is a classic chicken & egg problem. Furthermore, ribose breaks down in 40 days!! Molecules, in general, rather than complexifying, break down into their constituents, giving as a result, asphalt.
3. Considering these problems & facts, it is more reasonable to assume that an intelligent designer created life all at once, fully formed, rather a natural, stepwise process, based on chemical evolution, for which there is no evidence, that it happened, or could happen in principle.
B) The problem of the prebiotic origin of amino acids
1. Amino acids are of a very specific complex functional composition and made by cells in extremely sophisticated orchestrated metabolic pathways, which were not extant on the early earth. If abiogenesis were true, these biomolecules had to be prebiotically available and naturally occurring ( in non-enzyme-catalyzed ways by natural means ) and then somehow join in an organized way. Twelve of the proteinogenic amino acids were never produced in sufficient concentrations in any lab experiment. There was no selection process extant to sort out those amino acids best suited and used in life, amongst those that were not useful. There was potentially an unlimited number of different possible amino acid compositions extant prebiotically. (The amino acids alphabet used in life is more optimal and robust than 2 million tested alternative amino acid "alphabets")
2. There was no concentration process to collect the amino acids at one specific assembly site. There was no enantiomer selection process ( the homochirality problem). Amino acids would have disintegrated, rather than complexified There was no process to purify them.
3. Taken together, all these problems make an unguided origin of Amino Acids extremely unlikely. Making things for a specific purpose, for a distant goal, requires goal-directedness. We know that a) unguided random purposeless events are unlikely to the extreme to make specific purposeful elementary components to build large integrated macromolecular systems, and b) intelligence has goal-directedness. Bricks do not form from clay by themselves, and then line up to make walls. Someone made them.
C) The origin of Information stored in the genome.
1. Semiotic functional information is not a tangible entity, and as such, it is beyond the reach of, and cannot be created by any undirected physical process.
2. This is not an argument about probability. Conceptual semiotic information is simply beyond the sphere of influence of any undirected physical process. To suggest that a physical process can create semiotic code is like suggesting that a rainbow can write poetry... it is never going to happen! Physics and chemistry alone do not possess the tools to create a concept. The only cause capable of creating conceptual semiotic information is a conscious intelligent mind.
3. Since life depends on the vast quantity of semiotic information, life is no accident and provides powerful positive evidence that we have been designed. A scientist working at the cutting edge of our understanding of the programming information in biology, he described what he saw as an “alien technology written by an engineer a million times smarter than us”
D) The origin of the adapter, key, or process of some kind to exist prior to translation = ribosome
1. Ribosomes have the function to translate genetic information into proteins. According to Craig Venter, the ribosome is “an incredibly beautiful complex entity” which requires a minimum of 53 proteins. It is nothing if not an editorial perfectionist…the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products… They are molecular factories with complex machine-like operations. They carefully sense, transfer, and process, continually exchange and integrate information during the various steps of translation, within itself at a molecular scale, and amazingly, even make decisions. They communicate in a coordinated manner, and information is integrated and processed to enable an optimized ribosome activity. Strikingly, many of the ribosome functional properties go far beyond the skills of a simple mechanical machine. They can halt the translation process on the fly, and coordinate extremely complex movements. The whole system incorporates 11 ingenious error check and repair mechanisms, to guarantee faithful and accurate translation, which is life-essential.
2. For the assembly of this protein-making factory, consisting of multiple parts, the following is required: genetic information to produce the ribosome assembly proteins, chaperones, all ribosome subunits, and assembly cofactors. a full set of tRNA's, a full set of aminoacyl tRNA synthetases, the signal recognition particle, elongation factors, mRNA, etc. The individual parts must be available, precisely fit together, and assembly must be coordinated. A ribosome cannot perform its function unless all subparts are fully set up and interlocked.
3. The making of a translation machine makes only sense if there is a source code, and information to be translated. Eugene Koonin: Breaking the evolution of the translation system into incremental steps, each associated with a biologically plausible selective advantage is extremely difficult even within a speculative scheme let alone experimentally. Speaking of ribosomes, they are so well-structured that when broken down into their component parts by chemical catalysts (into long molecular fragments and more than fifty different proteins) they reform into a functioning ribosome as soon as the divisive chemical forces have been removed, independent of any enzymes or assembly machinery – and carry on working. Design some machinery that behaves like this and I personally will build a temple to your name! Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. The origin of the ribosome is better explained through a brilliant intelligent and powerful designer, rather than mindless natural processes by chance, or/and evolution since we observe all the time minds capabilities producing machines and factories.
E) The origin of the genetic code
1. A code is a system of rules where a symbol, letters, words, etc. are assigned to something else. Transmitting information, for example, can be done through the translation of the symbols of the alphabetic letters, to symbols of kanji, logographic characters used in Japan. In cells, the genetic code is the assignment ( a cipher) of 64 triplet codons to 20 amino acids.
2. Assigning meaning to characters through a code system, where symbols of one language are assigned to symbols of another language that mean the same, requires a common agreement of meaning. The assignment of triplet codons (triplet nucleotides) to amino acids must be pre-established by a mind.
3. Therefore, the origin of the genetic code is best explained by an intelligent designer.
1. PETER DOCKRILL: Scientists May Have Discovered The Shape of The Very First Proteins That Started Life 20 March 2020
2. BY F. H. c. CRICK: ON PROTEIN SYNTHESIS 1958
Prologue
In my previous book, I embarked upon the exploration of the RNA-DNA nexus into the complex and intricate process of RNA and DNA biosynthesis. We saw how these molecules are assembled from simple building blocks, going through an amazingly complex biosynthesis process. Now, in this next, follow-up book, I will describe the process of gene expression and the intricate details of DNA transcription, translation, and replication. The flow of information between DNA, RNA, and proteins is one of the most fundamental principles of molecular biology. It is called the "central dogma of molecular biology" and it describes how the genetic information in DNA is used to create proteins. The flow of information between DNA, RNA, and proteins is a complex and dynamic process.
Now, we stand at the threshold, ready to unveil the secrets hidden within the core processes that have withstood the test of time, essential for life's continuity. We embark on a journey, drawing from the insights of both scientific discovery and philosophical inquiry. Our perspective delves beyond the realm of chance and necessity, embracing a paradigm that transcends the boundaries of conventional thought –including the perspective of intelligent design. Here, within the pages of this tome, we shall explore the intricate web of molecular interactions, the hidden cogs in the machinery of life. We shall unveil the enigmatic intricacies of gene expression, the process by which the genetic code is translated into observable traits and characteristics, giving life its remarkable diversity and adaptability. We shall witness the awe-inspiring intricacies of transcription, where DNA's message is transcribed into its RNA counterpart, the molecular intermediary that bridges the genetic code to the synthesis of proteins. We shall traverse the landscape of translation, the transformative process that breathes life into genetic information, crafting the very proteins that sculpt the essence of an organism's identity. Furthermore, we shall have a close look into the amazing phenomenon of DNA replication, the faithful duplication of life's code, ensuring the continuity of generations and the endurance of species throughout the eons. But beyond mere observation, we shall seek to understand the underlying purpose, the masterful design, that seems to infuse these processes with unparalleled efficiency and elegance. What unseen forces shaped the mechanisms that safeguard and perpetuate life across the millennia? As we move forth into this intellectual odyssey, we are not driven by a desire to refute or dismiss a priori any possible views, but rather, to embrace the confluence of scientific inquiry and plausible philosophical inferences that frame our worldview. Herein lies the crux of our pursuit – to explore the boundaries of knowledge, guided by the tenets of reason, open to both the rigors of empirical evidence and permit the inference to the most plausible explanation of origins. May this journey of knowledge and insight illuminate the path toward understanding the profound mysteries of life's awe-inspiring complexity.
Gene expression carried out through the gene regulatory network, transcription, translation, and DNA replication, are all life-essential and indispensable processes performed by all living cells. Their significance lies in their crucial roles in maintaining the integrity and functionality of the cell, orchestrating the synthesis of proteins, and propagating genetic information across generations. The gene regulatory network governs the activity of genes within a cell, controlling when and to what extent genes are expressed. This intricate network ensures that specific genes are turned on or off in response to various internal and external cues. Through this regulation, cells can respond to changing conditions and environmental stimuli, enabling them to adapt and function optimally. Proper gene regulation is essential for cell differentiation, development, and maintaining the appropriate balance of cellular activities. Transcription is the process by which genetic information encoded in DNA is copied into RNA. This step is critical because DNA cannot directly interact with cellular machinery for protein synthesis. By transcribing the genetic code into RNA, the cell creates a mobile and accessible messenger that can carry the genetic information to the cytoplasm, where translation takes place. Translation is the process by which the genetic information in RNA is decoded to synthesize proteins. Proteins are the workhorses of the cell, carrying out various functions that govern cell structure, metabolism, signaling, and defense. All cellular processes, from energy production to cell division, rely on the actions of specific proteins. Without translation, the cell would be unable to produce the essential proteins required for its survival and function. DNA replication is the process by which the cell duplicates its genetic material to ensure that each daughter cell receives a complete set of genetic instructions during cell division. Accurate and faithful DNA replication is crucial to maintaining the genetic integrity of the cell and passing on genetic information to future generations. Errors in DNA replication can lead to mutations, which may result in genetic diseases or disruptions in cellular function. These processes are universal in living cells, from simple single-celled organisms to complex multicellular organisms, demonstrating their fundamental importance for life as we know it. They form the core mechanisms of heredity, allowing organisms to pass on genetic information to their offspring and ensuring the continuity of life across generations.
DNA requires an intermediate step, transcription, to produce mRNA (messenger RNA) before it can be translated into proteins. This process is essential due to the fundamental differences between DNA and the cellular machinery responsible for protein synthesis, namely ribosomes. DNA is a double-stranded molecule composed of a long sequence of nucleotides. It is a stable molecule that serves as the genetic blueprint, carrying the instructions for building and maintaining an organism. The architecture of the DNA double-strand exhibits clear logic and purpose-oriented design. It is a fundamental feature that plays a crucial role in the stability, replication, and transmission of genetic information. There are several reasons why DNA is necessary to be double-stranded: DNA is composed of four types of nucleotides: adenine (A), thymine (T), cytosine (C), and guanine (G). The double-stranded structure allows the two DNA strands to interact through complementary base pairing. Adenine always pairs with thymine (A-T), and cytosine always pairs with guanine (C-G). This complementary base pairing ensures that the information on one strand is precisely replicated on the other during DNA replication, which is essential for maintaining the accuracy of genetic information. The double-stranded structure of DNA imparts stability to the molecule. The hydrogen bonds between the complementary base pairs (A-T and C-G) hold the two strands together, providing strength to the overall structure. This stability prevents the DNA molecule from easily breaking apart, ensuring the preservation of genetic information over generations. During cell division, when a cell replicates, the DNA must be accurately copied to ensure that the daughter cells receive an identical set of genetic information. The double-stranded nature allows the DNA to serve as a template for semi-conservative replication. Each of the two original DNA strands serves as a template for the synthesis of a new complementary strand, resulting in two identical daughter DNA molecules. The double-stranded structure also facilitates DNA repair mechanisms. When DNA is damaged, cells have sophisticated repair systems that can recognize and correct errors or mutations. Having two complementary strands allows the cell to use the undamaged strand as a template to guide the repair process and maintain the integrity of the genetic information. While DNA replication ensures the faithful transmission of genetic information, the double-stranded structure also provides opportunities for genetic variation through mechanisms like mutations and recombination. These variations are important for adaptation, allowing organisms to respond to changing environments and contributing to the diversity of life. DNA's double-stranded structure and its location in the cell nucleus (in eukaryotes) or the nucleoid region (in prokaryotes) make it inaccessible to the cellular machinery responsible for protein synthesis, which is found in the cytoplasm. Transcription is necessary because mRNA is a single-stranded molecule that can easily pass through the nuclear membrane (in eukaryotes) or directly be accessible in the cytoplasm (in prokaryotes). RNA polymerase enzymes recognize specific regions on the DNA called promoters and initiate the synthesis of complementary RNA strands (mRNA) based on the DNA template. Once the mRNA is synthesized, it can exit the nucleus (in eukaryotes) or be immediately available for translation (in prokaryotes). Translation is the process by which mRNA is decoded to produce proteins. It occurs in ribosomes, which are complex cellular structures made up of RNA and proteins. Ribosomes read the sequence of nucleotides on the mRNA in sets of three (codons) and match each codon to a specific amino acid carried by transfer RNA (tRNA). This process leads to the synthesis of a polypeptide chain, which then folds into a functional protein. In this exploration of the marvels of life's intricacies, we embark on a journey through the unimaginably complex biosynthetic and manufacturing steps that lead to the creation and precise delivery of proteins, the building blocks of cellular function. Each step involves a symphony of molecular machines and processes, orchestrated with exquisite precision, raising intriguing questions about the origin and design of life.
The Central Dogma of Molecular Biology
The "central dogma of molecular biology" outlines a remarkable flow of information, a series of orchestrated steps from DNA to RNA to protein. This fundamental process serves as the foundation of life for all pro- and eukaryotic organisms, with only a few exceptions, like the reverse transcription observed in retroviruses' RNA genomes. Genomic DNA stands as the storied blueprint for life, housing the building plans of living beings. Genes are the segments of DNA that can be transcribed into RNA, and this transcription is carried out by specialized enzymes known as RNA polymerases. These remarkable enzymes catalyze the DNA-dependent synthesis of RNA, each serving different functions in the cell. RNA polymerase I is responsible for transcribing the genes encoding the three rRNAs, the structural components of ribosomes. Meanwhile, RNA polymerase III specializes in producing small RNA molecules, such as 5S rRNA and various tRNAs, which are crucial for essential cellular functions. These genes, associated with these two RNA polymerases, are often referred to as "housekeeping genes" due to their ubiquitous expression and relatively straightforward regulation. In contrast, RNA polymerase II, known as Pol II, undertakes the task of transcribing all 20,000 protein-coding genes and most non-coding RNAs (ncRNAs). Unlike the housekeeping genes, Pol II-transcribed genes are tightly regulated and respond to various intra- and extracellular signals. The regulation of Pol II's activity involves an intricate interplay of numerous transcription factors and other nuclear proteins, which serve as key players in the finely tuned symphony of gene expression. The Transcription Start Site (TSS) marks the first nucleotide transcribed into mRNA, defining the gene's 5'-end or "start." Analogously, the 3'-end of a gene is where RNA polymerases dissociate from the DNA template. Intergenic regions, existing between genes, represent a significant portion of the genome, constituting about 85% of the human genome. Only about 15% of the genome is transcribed into pre-mRNA, from which mature mRNA molecules are formed through the process of splicing. Splicing, occurring during transcription, skillfully removes introns and joins exons, producing mature mRNA molecules. These mature mRNA molecules are protected from degradation by capping and polyadenylation processes at their 5'- and 3'-ends, respectively. Subsequently, the mature mRNA molecules embark on a journey from the nucleus to the cytoplasm, utilizing ATP in an active transport process. Once in the cytoplasm, the ribosomes scan the mRNA from its 5'-end, seeking the start codon AUG—the signal for the initiation of protein translation. The ribosomes then assemble and skillfully translate the mRNA's genetic code into a polypeptide chain until they reach one of three stop codons (UAA, UAG, or UGA). The regions upstream and downstream of the start and stop codons are referred to as the 5'-UTR and 3'-UTR, respectively. Throughout the process of transcription, various protein complexes gather along the mRNA, forming a mature messenger ribonucleoprotein (mRNP) that is eventually exported to the cytoplasm. While all steps of transcription are essential, the initiation step is particularly controlled and regulated to ensure precise gene expression. Nevertheless, the later steps of gene expression, including mechanisms that halt gene expression, are also of great significance. In this context, non-coding RNAs (ncRNAs) play crucial regulatory roles.
The "central dogma of molecular biology" serves as a guiding principle, delineating a clear path through which information flows from DNA to RNA and eventually to proteins. This elegant and remarkable process governs the construction of all pro- and eukaryotic organisms, with only a handful of exceptions, such as the reverse transcription seen in the RNA genome of retroviruses. Imagine DNA as a vast reservoir of blueprints, meticulously storing the architectural plans for all living beings. Like a master architect, it holds the keys to life's intricate structures and functions. As this genetic blueprint unfolds, it orchestrates a symphony of molecular interactions, leading to the production of RNA—the messenger that conveys vital instructions to the cellular workforce. The journey from DNA to RNA is both captivating and precise. DNA's double-helix structure unwinds, revealing the genetic code like a well-guarded secret. As the genetic message is transcribed into RNA, it's akin to transcribing notes from a hidden musical score. This transcriptional process is the foundation upon which life's music is composed. But the journey doesn't end there; it's merely the prelude to the grand performance. The RNA, now brimming with the essence of DNA's instructions, embarks on a mission to the cellular factory—the ribosome. There, like a skilled conductor guiding an orchestra, the ribosome reads the RNA's musical notes, known as codons, and directs the choreography of protein synthesis. The result is a harmonious dance of amino acids assembling into intricate protein structures—a dance that shapes life's functions. Though some organisms defy the conventional rules, the majority adhere faithfully to this wondrous system of genetic information transfer. Reverse transcription in retroviruses, for instance, adds an intriguing twist to the tale, as RNA takes a U-turn, transforming back into DNA before embedding itself into the host genome. The intelligent setup is evident throughout this mesmerizing process. DNA stores the master blueprint behind the awe-inspiring diversity of life. The designer, the unseen programmer, has patiently sculpted and fine-tuned each unique arrangement.
The flow of information from DNA to RNA to protein follows a well-orchestrated process, akin to a finely tuned performance. The gene, the fundamental unit of heredity, begins its journey with the Transcription Start Site (TSS) as its starting point. The TSS, though lacking a defined sequence, marks the initiation of transcription into mRNA—a critical step that kickstarts the gene's story. As the gene body is transcribed, a single-stranded pre-mRNA is crafted, consisting of numbered green and brown exons, intermingled with intervening introns (i). These introns may seem like extraneous interruptions, but they play a vital role in the gene's tale. Like a skilled editor perfecting a manuscript, the process of splicing meticulously removes the intervening introns, leaving behind a streamlined mRNA ready to be polished for its grand debut. The mRNA is protected from external threats by the addition of a nucleotide cap at its 5'-end and a tail of hundreds of adenines at its 3'-end—a process known as polyadenylation (ii). Having undergone these meticulous preparations, the mature mRNA is now ready for its grand journey from the nucleus to the cytoplasm. This voyage is no passive affair; it requires the energy-consuming efforts of an active process, as the mRNA traverses the nuclear pores (iii). Once in the cytoplasm, the mRNA reveals its coded secrets to the waiting ribosomes—small and large subunits eager to begin the mesmerizing dance of protein translation. Scanning the mRNA from its 5'-end, they search for the elusive "start codon" AUG, where the translation spectacle commences. Step by step, amino acids are assembled into polypeptide chains until they reach the sequence UAA, UAG, or UGA—the "stop codons" that bring the translation to a graceful conclusion (iv). However, not all parts of the mRNA contribute to this performance. The sequences upstream of the start codon and downstream of the stop codon remain untranslated, forming the 5'- and 3'-UTRs—silent bookends to the protein-coding region. As the final act in this molecular play, the resulting polypeptide chains undergo a metamorphic transformation. They fold into intricate three-dimensional structures, becoming proteins—tools of life essential for a myriad of functions. Many proteins also undergo post-translational modifications, refining their functional profile to fulfill specific roles (v). Throughout this odyssey, the central dogma of molecular biology holds true, guiding the one-directional flow of information from DNA to RNA to protein. The brilliance of this mechanism, an exemplar of intelligent design, is evident in the precision and finesse with which it orchestrates life's symphony without falter or confusion.
Messenger RNA is a central player
The profound genius lies in the exquisite control over which recipes are "cooked" from this DNA-book in different cells, creating a remarkable diversity of cell types and functions in our bodies. At the heart of this orchestration are four major stages, each dedicated to shaping the destiny of messenger RNA (mRNA) molecules, the intermediaries that carry the instructions from the DNA to the protein factories called ribosomes: The process of transcription allows the DNA to express its recipes by copying the gene sequences into mRNA molecules. These mRNA molecules, carefully transcribed according to the DNA sequence, contain the precise instructions for constructing a specific protein. This step is akin to a meticulous copyist, ensuring that the recipes are reproduced accurately. Once transcribed, the mRNA molecules are transferred from the cell nucleus, a safeguarding vault where the precious DNA-book resides, into the bustling cytoplasm. This intra-cellular environment outside the nucleus serves as the bustling kitchen where proteins are assembled. The mRNA never ventures far from its secure nucleus, safeguarding the integrity of the DNA-book. The heart of the protein factory lies within the ribosome, an exquisite machine that reads the instructions encoded in the mRNA and crafts the corresponding protein. The sequence of amino acids, dictated by the mRNA nucleotide sequence, determines the nature and functionality of the protein. As the ribosome's precision unfolds, the proteins emerge, each contributing to the diverse repertoire of cellular functions that define who we are. Like a well-tuned system, mRNAs are not left to linger indefinitely. Instead, they are carefully turned over and degraded by specialized factors. Remarkably, the same factors that partake in transcription also contribute to mRNA decay, seamlessly connecting these intertwined processes. The intricate web of gene regulation that governs mRNA synthesis, transport, translation, and decay showcases a level of foresight and intentionality that evokes awe. The fine-tuned coordination of these processes ensures the harmonious functioning of our cells, each with its unique role to play in the symphony of life. The precision with which genes are regulated, allowing for specific proteins to be expressed in particular cells, demonstrates a purposeful design that speaks of an intelligent agency behind the curtain of life's grand theater.
Interdependence in the central dogma of life
At the beginning of this production line of proteins lies the gene regulatory network, a master conductor that determines when and which gene should be expressed. This network acts as the decision-maker, directing the flow of genetic information and ensuring that the right proteins are produced at the right time and in the right quantities. With the baton in the hands of the gene regulatory network, RNA polymerase takes the stage, initiating the transcription process. It carefully reads the genetic code and synthesizes RNA molecules that serve as messengers to convey genetic instructions. The production of RNA is not without scrutiny. Core polymerase and transcription factors act as vigilant quality checkers, ensuring that errors are detected and corrected so that the accurate genetic message is preserved. As the RNA strands emerge, they undergo a series of artistic modifications, including capping and splicing. These alterations provide stability and ensure that only the relevant portions of the genetic code are used, adding layers of complexity to the production process. In the progress, elongation of the RNA strands takes place, leading to cleavage and polyadenylation. These additional processes are critical for the final composition of the RNA and contribute to the precision of protein synthesis. Next, the ribosome takes center stage, where the choreography of initiation, completion, and protein folding unfolds. Each step is executed with grace and accuracy, showcasing the intricacy of the translation process. But the production of proteins is only part of the masterpiece. Protein targeting mechanisms ensure that each protein finds its way to the right cellular compartment, akin to a dancer finding their place on stage. No production is complete without quality control. Ribosome quality control and various checkpoints meticulously inspect the proteins, rejecting any flawed performances and preserving the integrity of cellular function. The production line continues with posttranslational processing in eukaryotic cells, where proteins undergo a series of modifications in the endoplasmic reticulum. Transmembrane and water-soluble proteins receive their final touches through glycosylation, further enhancing their functionality. At every step of this awe-inspiring journey, we witness the delicate interplay of molecular machines, each composed of numerous subunits and co-factors, working harmoniously to create and deliver proteins with remarkable precision. The complexity and interdependence of these processes present a challenge to the notion of unguided origins. Instead, they evoke a compelling case for intelligent design—a purposeful process crafted with extraordinary foresight.
The remarkable complexity and interdependence of the biological production line for protein synthesis pose an unbridgeable challenge to the idea of unguided origins. The intricate orchestration of numerous molecular machines and processes, each with specific functions and interactions, suggests a level of sophistication that goes beyond what could reasonably be expected from random, unguided mechanisms.
Each step in the production line serves a specific purpose and contributes to the accurate synthesis and delivery of proteins. The genetic code, stored in DNA and transferred through RNA, is a highly specific and information-rich language. Information theory suggests that the origin of complex information, like the genetic code, is most plausibly attributed to an intelligent source capable of encoding meaningful instructions. The production line's irreducible complexity refers to the idea that removing or altering any step would disrupt the entire process, rendering it non-functional. The system could not have self-assembled gradually through unguided events, as intermediate stages would lack functionality. The seamless coordination of molecular machines and processes implies a level of integrated design. For this complex production line to work effectively, all components must be in place and functioning together from the outset. Many of the steps in the production line, such as RNA splicing and protein folding, are tightly regulated and precisely controlled. The presence of intricate quality control mechanisms implies a purposeful design to ensure the proper functioning of the system. The ability of proteins to be targeted to specific cellular compartments further demonstrates the precision and foresight involved in the production process. This targeted delivery is crucial for the proper functioning of complex cellular structures. The production line's emergence would require the simultaneous appearance of multiple interdependent components, each with specific functions. The probability of these components arising together through unguided processes is exceedingly low, making intelligent design a more plausible explanation. To date, there is no comprehensive naturalistic explanation for the simultaneous emergence of the many complex processes and molecular machines involved in protein synthesis. The explanatory power of intelligent design arises from its ability to account for the specified complexity and interdependence observed in living systems.
An example of how science communicators of mainstream media rely on guesswork to explain the origin of these complex systems can be seen in the article from Peter Dockrill: Scientists May Have Discovered The Shape of The Very First Proteins That Started Life, published on 20 March 2020. 1 In the article, Dockrill attempts to explore the possible shape and configuration of the earliest building blocks of life, dating back billions of years. The study uses computer modeling to simulate the molecular arrangements of ancient proteins that no longer exist on Earth. The research seeks to shed light on life's origins. Throughout the article, Dockrill uses words like "could be," "might best fit," "hypothesize," and "think." This kind of language reflects the speculative nature of the research and the limitations of the approach. These are theories and hypotheses, not definitive conclusions. The study's findings are based on the comparison of existing 3D protein structures to infer a common ancestor. However, the lack of direct evidence from fossils or ancient protein samples makes it challenging to confidently determine the exact shape and structure of ancient proteins. Dockrill suggests that life's origins might have started with "small, simple peptides" that extracted energy from the environment. There is an immense complexity involved in the transition from non-living matter to the first living organisms. The formation of functional proteins and the emergence of cellular processes involve numerous intricate steps. The article mentions the potential detection of life on other planetary bodies based on abiotic chemistry and biosignatures. While this is an exciting area of astrobiology research, it is vital to differentiate between the existence of life and the potential for life to arise in specific environments. Conflating the two could lead to misconceptions about the nature of life's origin. The use of computer modeling in scientific research is valuable, but it also has limitations. Modeling is a tool for generating hypotheses and exploring possibilities, but it cannot provide definitive evidence without experimental validation.
Already in 1958, Francis Crick recognized the problem of the interdependence of the various molecular machine complexes required to synthesize proteins. He wrote:
The basic dilemma of protein synthesis ha8 been realized by many people, but it has been particularly aptly expressed by Dr A. L. Dounce (1956); My interest in templates, and the conviction of their necessity, originated from a question asked me on my Ph.D. oral examination by Professor J. B. Sumner. He enquired how I thought proteins might be synthesized. I gave what seemed the obvious answer, namely, that enzymes must be responsible. Professor Sumner then asked me the chemical nature of enzymes, and when I answered .that enzymes were proteins or contained proteins as essential components, he asked whether these enzyme proteins were synthesized by other enzymes and so on ad Infinitum. The dilemma remained in my mind, causing me to look for possible solutions that would be acceptable, at least from the standpoint of logic. The dilemma, of course, involves the specificity of the protein molecule, which doubtless depends to a considerable degree on the sequence of amino acids in the peptide chains of the protein. The problem is to find a reasonably simple mechanism that could account for specific sequences without demanding the presence of an ever-increasing number of new specific enzymes for the synthesis of each new protein molecule. It is thus clear that the synthesis of proteins must be radically different from the synthesis of polysaccharides, lipids, co-enzymes and other small molecules; that it must be relatively simple, and to a considerable extent uniform throughout Nature; that it must be highly specific, making few mistakes; and that in all probability it must be controlled at not too many removes by the genetic material of the organism. 2
Francis Crick's writings from 1958 demonstrate his early recognition of the problem of interdependence in protein synthesis. He grappled with the challenges posed by the specificity of the protein molecule and the need for a mechanism that could account for specific sequences without an infinite regression of enzymes. Crick acknowledged that the dilemma of protein synthesis had been realized by many people, and he referred to Dr. A. L. Dounce's expression of this dilemma in 1956. The central issue is how proteins, with their high specificity, are synthesized without requiring an ever-increasing number of new specific enzymes for each new protein molecule. Crick's Ph.D. oral examination with Professor J. B. Sumner led to a realization that enzymes, responsible for protein synthesis, were themselves proteins or contained proteins as essential components. This raised the question of whether these enzyme proteins were synthesized by other enzymes, potentially leading to an infinite regress of enzyme synthesis. Crick highlighted that the specificity of the protein molecule depends considerably on the sequence of amino acids in the peptide chains of the protein. This specificity is essential for their biological function and adds to the challenge of explaining their origin and synthesis. Crick emphasized the necessity of finding a reasonably simple mechanism that could account for specific sequences without requiring an excessive number of specific enzymes. This indicates his early understanding of the concept of irreducible complexity, wherein certain biological systems require all their components to be present and functional simultaneously. Crick speculated that protein synthesis must be controlled by the genetic material of the organism, suggesting the involvement of DNA and RNA in directing the synthesis of proteins. This foreshadows the central dogma of molecular biology, which elucidates the flow of genetic information in cells. Crick's writings from 1958 clearly demonstrate his early awareness of the interdependence and complexity involved in protein synthesis. He recognized the challenges posed by the specificity of proteins and the need for a mechanism that could account for their specific sequences without an infinite number of enzymes. Crick's insights laid the groundwork for further research in molecular biology and inspired ongoing investigations into the origins of life's complexity.
The astonishing complexity of biosyntheses and production-line-like manufacturing processes in living organisms is nothing short of a marvel. Each of these intricate steps demands an elaborate orchestra of molecular machines, intricately composed of numerous subunits and co-factors, working in perfect harmony to accomplish their tasks. These molecular machines are truly masterpieces of design, carefully crafted to carry out their functions with precision. Yet, the origin of such elaborate molecular machinery poses an enigmatic challenge—an irreducible catch-22 problem. Imagine a series of at least 25 unimaginably complex biosynthesis steps, each requiring specialized molecular machinery. These steps are akin to a manufacturing assembly line, where raw materials are transformed into exquisite end products. At the core of these processes are molecular machines, composed of intricate arrangements of subunits and co-factors, with each component playing a specific role. These machines work with unparalleled efficiency, manufacturing essential molecules, proteins, and structures that drive life's intricacies. The catch-22 arises from the interdependence of these molecular machines. Each machine requires specific subunits and co-factors to function effectively, yet these components themselves need prior processing and assembly to become fully operational. This intricate web of dependencies forms a complex puzzle—an irreducible challenge that seems impossible to solve without all the pieces in place. This catch-22 problem is like a chicken-and-egg scenario, where the existence of one component depends on another, and vice versa. One might wonder: how could these complex molecular machines come into existence without all the necessary components already assembled?
Following are the processes employed by the cell to produce proteins:
- the gene regulatory network "selects" when which gene is to be expressed
- initiation of transcription by RNA polymerase
- transcription error checking by core polymerase and transcription factors
- RNA capping
- elongation
- splicing
- cleavage
- polyadenylation and termination
- export from the nucleus to the cytosol
- initiation of protein synthesis (translation) in the ribosome
- completion of protein synthesis
- protein folding
- maturation
- ribosome quality control
- protein targeting to the right cellular compartment
- engaging the targeting machinery by the protein signal sequence
- call cargo proteins to load/unload the proteins to be transported
- assembly/disassembly of the translocation machinery
- various checkpoints for quality control and rejection of incorrect cargos
- translocation to the endoplasmic reticulum
- posttranslational process of proteins in the endoplasmic reticulum of transmembrane proteins and water-soluble proteins
- glycosylation of membrane proteins in the ER (endoplasmic reticulum)
- addition of oligosaccharides
- incorrectly folded proteins are exported from the ER, and degraded in the cytosol
- transport of the protein cargo to the end destinations and assembly
In order for evolution to start, this robot-like working machinery and assembly line must be in place, and fully operational. The origin of these machines cannot be explained through evolution. All it is left, are random chemical reactions, or intelligent design.
1. F
2. F -> A & B & C & D & E
3. A & B & C & D & E -> requires Intelligence
4. Therefore Intelligence
A: The RNA and DNA molecules
B: A set of 20 amino acids
C: Information, Biosemiotics ( instructional complex mRNA codon sequences transcribed from DNA )
D: Transcription and translation mechanism ( adapter, key, or process of some kind to exist prior to translation = ribosome )
E: Genetic Code
F: Functional proteins
1. Life depends on proteins (molecular machines) (D). Their function depends on the correct arrangement of a specified complex sequence of amino acids.
2. That depends on the existence of a specified set of RNAs and DNAs (A), amino acids (B), transcription through the RNA polymerase (D), and translation of genetic information (C) through the ribosome (D) and the genetic code (E), which assigns 61 codons and 3 start/stop codons to 20 amino acids
3. Instructional complex Information ( Biosemiotics: Semantics, Synthax, and pragmatics (C)) is only generated by intelligent beings with foresight. Only intelligence with foresight can conceptualize and instantiate complex machines with specific purposes, like translation using adapter keys (ribosome, tRNA, aminoacyl tRNA synthetases (D)) All codes require arbitrary values being assigned and determined by an agency to represent something else (genetic code (E)).
4. Therefore, Proteins being the product of semiotics/algorithmic information including transcription through RNA polymerase and translation through the ribosome and the genetic code, and the manufacturing system ( information directing manufacturing ) are most probably the product of a super powerful intelligent designer.
The problem of getting functional proteins is manyfold. Here are a few of them:
A) The problem of the prebiotic origin of the RNA and DNA molecule
1. DNA ( Deoxyribonucleotides) are one of the four fundamental macromolecules used in every single cell, in all life forms, and in viruses
2. DNA is composed of the base, ribose ( the backbone), and phosphorus. A complex web of minimally over 400 enzymes are required to make the basic building blocks, including RNA and DNA, in the cell. This machinery was not extant prebiotically.
RNA and DNA is required to make the enzymes, that are involved in synthesizing RNA and DNA. But these very enzymes are required to make RNA and DNA? This is a classic chicken & egg problem. Furthermore, ribose breaks down in 40 days!! Molecules, in general, rather than complexifying, break down into their constituents, giving as a result, asphalt.
3. Considering these problems & facts, it is more reasonable to assume that an intelligent designer created life all at once, fully formed, rather a natural, stepwise process, based on chemical evolution, for which there is no evidence, that it happened, or could happen in principle.
B) The problem of the prebiotic origin of amino acids
1. Amino acids are of a very specific complex functional composition and made by cells in extremely sophisticated orchestrated metabolic pathways, which were not extant on the early earth. If abiogenesis were true, these biomolecules had to be prebiotically available and naturally occurring ( in non-enzyme-catalyzed ways by natural means ) and then somehow join in an organized way. Twelve of the proteinogenic amino acids were never produced in sufficient concentrations in any lab experiment. There was no selection process extant to sort out those amino acids best suited and used in life, amongst those that were not useful. There was potentially an unlimited number of different possible amino acid compositions extant prebiotically. (The amino acids alphabet used in life is more optimal and robust than 2 million tested alternative amino acid "alphabets")
2. There was no concentration process to collect the amino acids at one specific assembly site. There was no enantiomer selection process ( the homochirality problem). Amino acids would have disintegrated, rather than complexified There was no process to purify them.
3. Taken together, all these problems make an unguided origin of Amino Acids extremely unlikely. Making things for a specific purpose, for a distant goal, requires goal-directedness. We know that a) unguided random purposeless events are unlikely to the extreme to make specific purposeful elementary components to build large integrated macromolecular systems, and b) intelligence has goal-directedness. Bricks do not form from clay by themselves, and then line up to make walls. Someone made them.
C) The origin of Information stored in the genome.
1. Semiotic functional information is not a tangible entity, and as such, it is beyond the reach of, and cannot be created by any undirected physical process.
2. This is not an argument about probability. Conceptual semiotic information is simply beyond the sphere of influence of any undirected physical process. To suggest that a physical process can create semiotic code is like suggesting that a rainbow can write poetry... it is never going to happen! Physics and chemistry alone do not possess the tools to create a concept. The only cause capable of creating conceptual semiotic information is a conscious intelligent mind.
3. Since life depends on the vast quantity of semiotic information, life is no accident and provides powerful positive evidence that we have been designed. A scientist working at the cutting edge of our understanding of the programming information in biology, he described what he saw as an “alien technology written by an engineer a million times smarter than us”
D) The origin of the adapter, key, or process of some kind to exist prior to translation = ribosome
1. Ribosomes have the function to translate genetic information into proteins. According to Craig Venter, the ribosome is “an incredibly beautiful complex entity” which requires a minimum of 53 proteins. It is nothing if not an editorial perfectionist…the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products… They are molecular factories with complex machine-like operations. They carefully sense, transfer, and process, continually exchange and integrate information during the various steps of translation, within itself at a molecular scale, and amazingly, even make decisions. They communicate in a coordinated manner, and information is integrated and processed to enable an optimized ribosome activity. Strikingly, many of the ribosome functional properties go far beyond the skills of a simple mechanical machine. They can halt the translation process on the fly, and coordinate extremely complex movements. The whole system incorporates 11 ingenious error check and repair mechanisms, to guarantee faithful and accurate translation, which is life-essential.
2. For the assembly of this protein-making factory, consisting of multiple parts, the following is required: genetic information to produce the ribosome assembly proteins, chaperones, all ribosome subunits, and assembly cofactors. a full set of tRNA's, a full set of aminoacyl tRNA synthetases, the signal recognition particle, elongation factors, mRNA, etc. The individual parts must be available, precisely fit together, and assembly must be coordinated. A ribosome cannot perform its function unless all subparts are fully set up and interlocked.
3. The making of a translation machine makes only sense if there is a source code, and information to be translated. Eugene Koonin: Breaking the evolution of the translation system into incremental steps, each associated with a biologically plausible selective advantage is extremely difficult even within a speculative scheme let alone experimentally. Speaking of ribosomes, they are so well-structured that when broken down into their component parts by chemical catalysts (into long molecular fragments and more than fifty different proteins) they reform into a functioning ribosome as soon as the divisive chemical forces have been removed, independent of any enzymes or assembly machinery – and carry on working. Design some machinery that behaves like this and I personally will build a temple to your name! Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. The origin of the ribosome is better explained through a brilliant intelligent and powerful designer, rather than mindless natural processes by chance, or/and evolution since we observe all the time minds capabilities producing machines and factories.
E) The origin of the genetic code
1. A code is a system of rules where a symbol, letters, words, etc. are assigned to something else. Transmitting information, for example, can be done through the translation of the symbols of the alphabetic letters, to symbols of kanji, logographic characters used in Japan. In cells, the genetic code is the assignment ( a cipher) of 64 triplet codons to 20 amino acids.
2. Assigning meaning to characters through a code system, where symbols of one language are assigned to symbols of another language that mean the same, requires a common agreement of meaning. The assignment of triplet codons (triplet nucleotides) to amino acids must be pre-established by a mind.
3. Therefore, the origin of the genetic code is best explained by an intelligent designer.
1. PETER DOCKRILL: Scientists May Have Discovered The Shape of The Very First Proteins That Started Life 20 March 2020
2. BY F. H. c. CRICK: ON PROTEIN SYNTHESIS 1958
Last edited by Otangelo on Wed 2 Aug 2023 - 18:27; edited 18 times in total
