Something new, something old.

Proteins in a cell have their functions. Their functions stem from their protein shape. Therefore, denaturing kills their function without altering their amino acid sequence. Their shape is the source of their functions.

Which comes first, shape or function?

The shape of a protein is primarily controlled by its amino acid sequence. The amino acid sequence is encoded in the DNA sequence in the genome.  Thus, the shape is encoded in the genome as a gene.

How about functions? What are functions?

Functions emerge (or are recognized) in a reproducible process. Playing a role means reproducibly conducting a specific action within the context of a reproducible process. This specific action is the function.

A cell is a pack of reproducible processes. Each reproducible process is called a mechanism or a pathway. Each mechanism or pathway is a cascade of specific actions mediated by the functions of specific proteins. When a protein has a specific role in a reproducible cellular process, that is its function. The shape of a protein mediates its function.

Then, which comes first, shape or function?

In human societies, functions often appear to emerge first. It is better to rephrase functions as intentions, purposes, or goals, since functions are part of the processes for achieving them. Once a goal is set, roles and functions emerge. An intention sets a goal or purpose. Without a goal, no function.  

Functions emerge in the putative process to achieve the intention. A man-made machine is designed based on an intention. Its parts are intentionally assembled. Each part has its function, and the machine itself has functions. A watch is intended to report the time – this is its function. Each part of a watch, such as a gear, a band or clock hands, has its own function based on its shape. Functions are reproducible actions within a reproducible process.

In a cell, who designed the shape? Is there any intention, goal or purpose of a cell or in a cell?

Does a cell have a goal or purpose? Does a cell have an intention?  Do functions design the shape, or conversely, does the shape create functions?

The shape can create functions. More precisely, the shape creates a reproducible consequence. A reproducible process emerges from the shape. Therefore, the word ‘function’ can even be used in inanimate chemical reactions. ‘Catalyst’ is the name of the molecule that facilitates a specific reaction, reproducibly – a catalyst’s action is its function.  A catalyst functions because of its unique molecular shape and properties, reproducibly facilitating a chemical reaction.

The reproducibility of one chemical reaction does not create a living organism. However, a series of multiple reproducible chemical reactions accidentally forming a circuit could be. A living organism is a circuit that incorporates growth-replicate-reproduce within semipermeable compartments. The cyclic momentum of chemical reactions within the circuit is alive. Its stoppage is death. The cyclic momentum is maintained as long as the proteins (catalysts) have their own shape and their proper geometry within a cell.

Functions emerge (or are recognized) within a reproducible process. When multiple reproducible processes form a circuit, the functions are recognized within its perpetual cyclic momentum.  Protein function arises from protein shape. Their amino acid sequence primarily dictates their shape. Their amino acid sequence is encoded on chromosomes as the DNA sequence.  This DNA sequence is the gene.  The accidental formation of a circuit defines the genes in a random DNA sequence because it encodes protein shapes involved in the cyclic momentum.

Which comes first, the shape, the gene or the cyclic momentum?

The various shapes should have existed and been encoded in the DNA sequence prior to the emergence of life. There must have been spontaneously initiated chemical reaction cascades with momentum. But none were cyclic. Therefore, no genes. The shapes interacted randomly with each other and with environmental molecules. Random spontaneous pulsatory momenta by shape-shape encounters.  

The great properties of DNA are the complementary sequence of a double-stranded polymer, and no constraint in the order of dNTPs: A, C, G, and T and in their length. The polymer can form random sequences of varying lengths that are replicable.  Various shapes are encoded in the replicable DNA sequence.  A random sequence generates many different shapes in proteins, which may have unique functions in chemical reactions.

The double-stranded complementary DNA polymer with the triplet codon system is an amazing condensed information carrier. In the same length of a DNA polymer, six coding patterns exist because of the forward vs reverse strand and codon frames 1, 2 and 3. For example, in a 30 bp DNA polymer, six kinds of 10-amino acid peptides are theoretically available. Suppose the codon is a duplet, four kinds with 15-amino acid peptides. Please do not forget that, at the onset of life, there were no mechanisms of transcriptional and translational regulation, but only chemical linkages. Nothing was sophisticated.

Additionally, the triplet codon system allows 64 variations of tRNA-amino acid complexes, while the duplet codon system allows 16 variations.  My hypothesis is that the codon system began as a duplet with one blank base as a spacer; therefore, the third base in a codon is the least important. But this looseness permitted the later development of third-base use. Nothing was precise or efficient, but it was sufficient for probabilistic reproducibility. The beginning of cyclic momentum was accidental, probabilistic and primitive. After the first cyclic momentum, the second could occur probabilistically.   

A long random DNA sequence generates many shapes using six potential open reading frames.  Many random shapes facilitate chemical reactions. When some of these shapes create an accidental circuit that incorporates growth-replication-reproduction with the abundant resources of their local environment, the first life emerges. Immediately upon the emergence of the first cycle, the genes were defined within the long, random sequence as those encoding shapes that performed functions in the circuit. As long as it stays in the same environment of the first cyclic event, the second and third cyclic events could happen in a probabilistic manner. Nothing precisely occurs in each process of growth-replication-reproduction, but only cycled ones have another chance of cycling. Errors in the sequence are constantly introduced because replication was not precise. The primitive codon system is also not precise, but good enough for another cycle. When the essential shapes are compromised, the cyclic momentum disappears. The end. All other errors, as long as the cyclic momentum is sustained, are tolerated.  Whatever the changes that support the robustness of the cyclic momentum (i.e. minimizing the risk of terminal lethal errors), the circuits are likely to be sustained.

In early cycling, many unnecessary sequences for cycling must be present in the long random DNA sequence.  It means many unnecessary shapes for cycling are present in a cell. The original long, random sequence, encoding many random shapes, is the necessity for the first cyclic momentum to emerge within a complex network of chemical reactions. However, as soon as the first cyclic momentum occurs (i.e., the first circuit), the complexity creates problems for reproducibility. Since the first circuitry pattern is not the obvious simple route, many other putative patterns and wrong routes are likely available.  The first circuit is the only validated one and has the highest reproducible probability in the same environment.

The first accidental circuit separates the DNA sequence into genic and non-genic regions, despite both areas carrying various shapes. Non-genic sequences encoding unnecessary shapes are confusing and may block the functions of the correct shapes. Removing them will reduce the risk of cycling failure.

Additionally, during primitive DNA replication, errors are inevitable. Errors in gene sequences can change the shapes of the encoded proteins. Changes in protein shape may affect the reproducibility of chemical reactions. On the other hand, errors in non-genic regions should theoretically be tolerated; however, they also have a risk of accidentally creating a new shape that can interfere with the original chemical reactions for cycling. Eliminating unnecessary sequences is the best risk-control option to keep the cyclic momentum going robustly.

A messy, chaotic collection of shapes allows the circuit to form. However, for the circuit's reproducibility, this messiness should be cleared and eliminated. Messiness is a risk factor for cycle failure.

Not intentionally (importantly, no intention at all here), but error-sensitive cycling entities gradually disappear from cycling. Then, the cycling entities that gain robustness continue to do so. Simply, many errors in replication. When the new entity cannot maintain a probability of reproducible cycling above the termination threshold, it disappears—the balance between the probabilities of cycling and collapsing.

Consequently, no extra sequence, except for genes in the genome, is the best option to deal with internal error rates. What this means is that the mess is cleaned up, and there are only shapes that have functions in cycling in a cell.  The potential risk of creating unnecessary shapes is minimized.  The cyclic momentum continues. Nothing is intentional but consequential because of the cyclic momentum within the erroneous, replicable reproducing system. 

Importantly, during this trimming process, the original environment should be highly stable, as the cyclic momentum of the first circuit depends entirely on the abundant resources in the local, adjacent environment. There are no external risk factors. Therefore, trimming of the unnecessary was possible. In analogy, you do not need an umbrella in the desert.

I believe this is the process that occurred in the emergence of the first prokaryotes. Without life, the environment is stable. Stably chaotic.  In this stable condition, the cyclic momentum of chemical reactions encoded in the DNA polymer emerged. Importantly, in the chaotic random collection of shapes, the possible circuit pattern is not just one. In addition, the trimming process also has multiple possibilities without compromising the cyclic momentum. 

For example, imagine transportation in a city: many routes (including detours) and many transportation options (walk, bicycle, bus, etc.).  In a complex network, whatever happens, you can find a way to reach the point you want to go.  Many detours mean robust. However, simultaneously, many detours can make a visitor easily get lost, too. If there are no detours, no one gets lost.  Highly efficient but vulnerable to interference.

If the environment is stable in space and time, no detour is required. If it is unstable, detours are needed; otherwise, all cycling entities disappear in one environmental fluctuation. I can assume the environment at the emergence of prokaryotes was stable, since prokaryotes trimmed all non-genic regions. The other side of the same coin is that, therefore, they have been staying in the same form because of no extra sequence to create something new.  Prokaryotes are highly efficient cycling organisms in their suitable environments. My guess about what separated survivors and non-survivors was whether they could pause the cycle or not during environmental fluctuations.

The DNA sequence is the origin of shapes that facilitate chemical reactions.  Through trimming of DNA, no extra, unnecessary shapes in individual prokaryotes. To overcome this limit, prokaryotes occasionally exchange small DNA sequences between strains. This brings new shapes into individual cells. For example, antibiotic properties are exchanged between distinct bacteria in this way. This is called horizontal gene transfer, in contrast to vertical transfer, which refers to traditional inheritance from the parent. Hybridization/fusion of two species creates a mess in the hybrids. Multiple species fusion will be further messier and chaotic. However, this is an opportunity to find a new circuitry pathway from a chaotic mess and to create novel retrimming opportunities, despite most being failures. On a rare occasion, this could lead to accidentally overcoming the previous environmental constraint. The adjacent uninhabitable area due to toxic conditions, no resources, or its climate might become livable by a new circuit from the messy chaos and trimming—the emergence of a new species.  

I believe that eukaryotes emerged by the fusion of multiple prokaryotes, including mitochondria and chloroplasts. Mitochondria and chloroplasts kept their DNA in their compartments. I assumed that all others were shared in the nucleus. My guess is that the subcellular membranous organelles are the remains of the individual original prokaryotes. Through chaotic fusions, toxic oxygen for prokaryotes became a usable, essential, and abundant resource for eukaryotes.

Once the first eukaryote finds the circuit for cyclic momentum, the chaotic long DNA sequence is not necessary anymore. Trimming begins. However, probably due to the presence of prokaryotes (i.e., living organisms) in the environment, environmental stability is less than it was when prokaryotes emerged. The fluctuation in environmental conditions made trimming incomplete, because the necessity of individual genes also fluctuates along with environmental fluctuation. The unnecessary detours under normal conditions cannot be eliminated, but should be kept for the time of necessity. However, they should be hidden to prevent confusion under normal conditions. I assumed that this navigated the emergence of mechanisms for controlling gene and protein expression.  The unnecessary sequence for the normal standard moment is suppressed or silenced, but not eliminated. The unnecessary sequence could be necessary in an emergency.  It is reasonable to assume that, at the onset of prokaryotes, internal errors were the primary cause of cycle termination. After internal errors became manageable, the cycle termination was due to the external environment. Keeping the extra DNA sequence provides robustness against external environmental fluctuations and, overall, lowers the risk of termination.  

The new long DNA sequence offers the potential for new circuit discovery, but also carries the risk of confusion and termination.  This also offers to develop multicellularity from unicellularity.  Multicellularity is not better in cycling, but it is robust as an organism. For example, the coelom, an internal cavity, provides a new shared compartment that is separated from the environment.  Through cooperation and division of labour, the organism can live in previously harsh, unlivable conditions. Symbiosis is also in the same line. Collaboration and sharing allow the participants to survive outside of the previous livable. No need to be better in the original environment. But the new uniqueness as a whole permits living in the previously unlivable.

When a new species emerges, it always makes the previous unusable usable. This change occurs because of the novel editions of the DNA sequence.  The novel editions of DNA create new shapes, new shape-complex combinations and new patterns in geometry within a cell and within an organism.  These geometrical changes permit the use of resources that no one else could have used previously.

Because of the extra DNA sequence and development of transcriptional and translational mechanisms, an organism can create different states of cells -  differentiation.  The production of shapes encoded in the genome is tightly controlled under energy-dependent transcriptional regulation.  The unnecessary shapes are silenced and suppressed. Therefore, the only necessary shapes are produced, which have specific functions and are encoded as genes.

Modern technologies have revealed the existence of cryptic transcripts and peptides derived from traditionally recognized non-genic regions. Shapes in a cell are not limited to the derivatives of genes. Small peptides encoded in non-coding RNAs, including intronic RNAs, are produced in the cell under stressed conditions, such as viral infection and cancer.  Codon frame usage can be changed. Out-of-frame products are also produced.  All of these peptides are new shapes. New shapes can create confusion and interruptions, but can also permit searching for new routes to address cellular stress.  

When the mechanisms that suppress the chaotic shapes encoded in the genome are compromised, the hidden shapes are released into the cell.  Those mechanisms play a role in the fidelity of chemical reactions at each biological step.  Usually, cells that cannot maintain fidelity die by apoptosis, using an energy-dependent mechanism. However, when this self-dying mechanism is compromised, the cell cannot die, and the newly released chaotic shapes disrupt its normal activity but also provide detours to overcome cellular stress.

Interestingly, these cryptic peptides are now recognized as potential cancer-specific antigens for vaccination. They are unique shapes that originated from their own genome but are never expressed under normal conditions; however, under stress environments, they arise when energy-dependent, sophisticated suppressive mechanisms are compromised.

Life is fragile, but simultaneously robust.  Living organisms are nested layers of complex networks, governed by shape.  Robustness is the key of life continuity from its beginning.  A complex network has many detours to compensate against insults. The upper nested layer of a complex network can compensate for the lower-layer deficiency. There are multiple compensatory abilities within a single layer and between adjacent layers in multicellularity.

Chaos created cyclic momentum. The cyclic momentum trimmed the chaos.  Animals have developed mechanisms to suppress and silence the chaos with extra energy rather than trimming. During development, the genome is perfectly choreographed to structurally and chemically modify unnecessary sequences, thereby suppressing and silencing them.

Development is the process of creating upper layers from a single cell, to tissues, organs and an organism with physiological networks.  From an individual human to a family, a local community, a working company, a nation, and the globe.  Human societies are also built from chaos into a network. A lower network is nested in an upper network. Bottoms up. Compensating and supporting each other allowed us to explore uncharted areas, zones or probabilities.

The chaos of shapes initiated the first cyclic momentum. Cyclic momentum imposes order, and mechanisms are built to suppress chaos for efficiency and reproducibility. However, the hidden chaos is an infinite probability of new routes of cyclic momentum.

Something new emerges from something very old.