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What Might Be a Cell’s minimal requirement of parts ?

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What might be a Cell’s minimal requirement of parts ?  1

http://reasonandscience.heavenforum.org/t2110-what-might-be-a-protocells-minimal-requirement-of-parts

How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept
https://www.ncbi.nlm.nih.gov/books/NBK2227/
Several theoretical and experimental studies have endeavored to derive the minimal set of genes that are necessary and sufficient to sustain a functioning cell under ideal conditions, that is, in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. A comparison of the first two completed bacterial genomes, those of the parasites Haemophilus influenzae and Mycoplasma genitalium, produced a version of the minimal gene set consisting of ~250 genes.

Following  irreducible processes and parts  are required to keep cells alive, and illustrate mount improbable to get life a first go: 
Reproduction. Reproduction is essential for the survival of all living things.
Metabolism. Enzymatic activity allows a cell to respond to changing environmental demands and regulate its metabolic pathways, both of which are essential to cell survival. 
Nutrition. This is closely related to metabolism. Seal up a living organism in a box for long enough and in due course it will cease to function and eventually die. Nutrients are essential for life. 
Complexity. All known forms of life are amazingly complex. Even single-celled organisms such as bacteria are veritable beehives of activity involving millions of components. 
Organization. Maybe it is not complexity per se that is significant, but organized complexity. 
Growth and development. Individual organisms grow and ecosystems tend to spread (if conditions are right). 
Information content. In recent years scientists have stressed the analogy between living organisms and computers. Crucially, the information needed to replicate an organism is passed on in the genes from parent to offspring. 
Hardware/software entanglement. All life of the sort found on Earth stems from a deal struck between two very different classes of molecules: nucleic acids and proteins. 
Permanence and change. A further paradox of life concerns the strange conjunction of permanence and change.
Sensitivity. All organisms respond to stimuli— though not always to the same stimuli in the same ways.
Regulation. All organisms have regulatory mechanisms that coordinate internal processes.

For a nonliving system, questions about irreducible complexity are even more challenging for a totally natural non-design scenario, because natural selection — which is the main mechanism of Darwinian evolution — cannot exist until a system can reproduce.  For an origin of life we can think about the minimal complexity that would be required for reproduction and other basic life-functions.  Most scientists think this would require hundreds of biomolecular parts.  And current science has no plausible theories to explain how the minimal complexity required for life (and the beginning of biological natural selection) could have been produced by natural process before the beginning of biological natural selection.

In order to make life, and specially multicellular complex life,  the building blocks of life, cells, have to be made, which are the tiniest living entities. To build  cells requires information and programming, complex protein manufacturing machines and assembly lines, energy, nutrient supply chains, quality control , waste bins, ability to adapt to the environment and to react to stimuli, ability of replicating, and housing ( the cell membrane ). 

“The complexity of the simplest known type of cell is so great that it is impossible to accept that such an object could have been thrown together suddenly by some kind of freakish, vastly improbable, event. Such an occurrence would be indistinguishable from a miracle.” 
― Michael Denton, Evolution: A Theory In Crisis

Determination of the Core of a Minimal Bacterial Gene Set
http://mmbr.asm.org/content/68/3/518.full.pdf
Based on the conjoint analysis of several computational and experimental strategies designed to define the minimal set of protein-coding genes that are necessary to maintain a functional bacterial cell, we propose a minimal gene set composed of 206 genes. Such a gene set will be able to sustain the main vital functions of a hypothetical simplest bacterial cell.

How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept
https://www.ncbi.nlm.nih.gov/books/NBK2227/
Several theoretical and experimental studies have endeavored to derive the minimal set of genes that are necessary and sufficient to sustain a functioning cell under ideal conditions, that is, in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. A comparison of the first two completed bacterial genomes, those of the parasites Haemophilus influenzae and Mycoplasma genitalium, produced a version of the minimal gene set consisting of ~250 genes.




A common feature of all life forms is their ability to maintain homeostasis in a given environment. Moreover, to accomplish cellular growth and division, a minimal cell would also require the ability to transform and assemble
its building blocks using the energy provided by the environment. It seems, therefore, that a minimal cell would require a minimal metabolism to fulfill both essential aspects. A first approximation to this core metabolism is provided by the analysis of the enzymatic functions encoded by the theoretically inferred minimal gene set from the abovementioned combined approach. Figure 16.1 (color plate 12)



provides representation of the metabolic network encoded by the theoretically inferred minimal gene set, which is thought to comprise the minimal set of metabolic reactions to sustain a bacterial cell under ideal nutrient supply conditions (i.e., glucose, fatty acids, amino acids, nucleobases, and vitamins). The comparison of this theoretically inferred minimal metabolism, in terms of metabolic capacities, with naturally reduced genomes reveals many parallels, since the procedure to determine this minimal set includes genes that are shared by most endosymbiotic bacteria. In the minimal gene set, the intermediary metabolism is mainly reduced to ATP synthesis by substrate-level phosphorylation during glycolysis and the nonoxidative pentose phosphate pathway, whereas amino acid biosynthesis is virtually absent. So it is with de novo biosynthesis of nucleotides, although the complete salvage pathways for most of them can be found. Lipid biosynthesis is limited to condensation of fatty acids with glycerol phosphate, and there are no pathways for biosynthesis of fatty acids. Altogether the minimal metabolic core seems devoted to the production of energy from glucose and the interconversion, rather than the net biosynthesis, of essential cellular building blocks, most of which would be readily provided by a rich environment. However, adding some complexity to this heterotrophic metabolism, one could envisage a hypothetical autotrophic minimal metabolism, like the one conjectured by Benner (1999).

MarcelloBarbieri Code Biology A New Science of Life , page 26
Organic information is an irreducible entity, because it cannot be described by anything simpler than its sequence, and the same is true for organic meaning, which cannot be defined by anything simpler than its coding rules.  Organic information and organic meaning, in short, belong to the same class of entities because they have the same defining characteristics: they both are objectivebut- not-measurable entities, they both are fundamental entities because they cannot be reduced to anything simpler. They are the twin pillars of life because organic information comes from the copying process that produces genes, while organic meaning comes from the coding process that generates proteins.

A primitive cell like an E. coli bacteria - one of the simplest life forms in existence today -- is amazingly complex.

Proteins are essential building blocks of living cells; indeed, life can be viewed as resulting substantially from the chemical activity of proteins. Because of their importance, it is hardly surprising that ancestors for most proteins observed today were already present at the time of the 'last common ancestor', a primordial organism from which all life on Earth is descended. How did the first proteins arise? How can we bring a taxonomic order to the diversity of forms that evolved from them? These two questions are at the center of our scientific efforts, on which we bring to bear methods in bioinformatics, protein biochemistry and structural biology.

Based on the conjoint analysis of several computational and experimental strategies designed to define the minimal set of protein-coding genes that are necessary to maintain a functional bacterial cell, we propose a minimal gene set composed of 206 genes. Such a gene set will be able to sustain the main
vital functions of a hypothetical simplest bacterial cell with the following features.

(i) A virtually complete DNA replication machinery, composed of one nucleoid DNA binding protein, SSB, DNA helicase, primase, gyrase, polymerase III, and ligase. No initiation and recruiting proteins seem to be essential, and the DNA gyrase is the only topoisomerase included, which should perform
both replication and chromosome segregation functions.

(ii) A very rudimentary system for DNA repair, including only one endonuclease, one exonuclease, and a uracyl-DNA glycosylase.

(iii) A virtually complete transcriptional machinery, including the three subunits of the RNA polymerase, a factor, an RNA helicase, and four transcriptional factors (with elongation, antitermination, and transcription-translation coupling functions). Regulation of transcription does not appear to be essential in bacteria with reduced genomes, and therefore the minimal gene set does not contain any transcriptional regulators.

(iv) A nearly complete translational system. It contains the 20 aminoacyl-tRNA synthases, a methionyl-tRNA formyltransferase, five enzymes involved in tRNA maturation and modification, 50 ribosomal proteins (31 proteins for the large ribosomal subunit and 19 proteins for the small one), six proteins necessary for ribosome function and maturation (four of which are GTP binding proteins whose specific function is not well known), 12 translation factors, and 2 RNases involved in RNA degradation.

(v) Protein-processing, -folding, secretion, and degradation functions are performed by at least three proteins for posttranslational modification, two molecular chaperone systems (GroEL/S and DnaK/DnaJ/GrpE), six components of the translocase machinery (including the signal recognition particle, its receptor, the three essential components of the translocase channel, and a signal peptidase), one endopeptidase, and two proteases.

(vi) Cell division can be driven by FtsZ only, considering that, in a protected environment, the cell wall might not be necessary for cellular structure.

(vii) A basic substrate transport machinery cannot be clearly defined, based on our current knowledge. Although it appears that several cation and ABC transporters are always present in all analyzed bacteria, we have included in the minimal set only a PTS for glucose transport and a phosphate transporter. Further analysis should be performed to define a more complete set of transporters.

(viii) The energetic metabolism is based on ATP synthesis by glycolytic substrate-level phosphorylation.

(ix) The nonoxidative branch of the pentose pathway contains three enzymes (ribulose-phosphate epimerase, ribosephosphate isomerase, and transketolase), allowing the synthesis of pentoses (PRPP) from trioses or hexoses.

(x) No biosynthetic pathways for amino acids, since we suppose that they can be provided by the environment.

(xi) Lipid biosynthesis is reduced to the biosynthesis of phosphatidylethanolamine from the glycolytic intermediate dihydroxyacetone phosphate and activated fatty acids provided by the environment.

(xii) Nucleotide biosynthesis proceeds through the salvage pathways, from PRPP and the free bases adenine, guanine, and uracil, which are obtained from the environment.

(xiii) Most cofactor precursors (i.e., vitamins) are provided by the environment. Our proposed minimal cell performs only the steps for the syntheses of the strictly necessary coenzymes tetrahydrofolate, NAD, flavin aderine dinucleotide, thiamine diphosphate, pyridoxal phosphate, and CoA.




Johnson DE 2010, Programming of Life, p37&49.
life's original alphabet must have used a coding system at least as symbolically complex as the current codon alphabet. There has been no feasible natural explanation proposed to produce such an alphabet since chance or physicality cannot produce functional information or a coding system, let alone a system as complex as that in life"

Jack T. Trevors – Theoretical Biology & Medical Modelling, Vol. 2, 11 August 2005, page 8 1
“No man-made program comes close to the technical brilliance of even Mycoplasmal genetic algorithms. Mycoplasmas are the simplest known organism with the smallest known genome, to date. How was its genome and other living organisms’ genomes programmed?”


The argument of the cell
1. At least 239 proteins are required as building blocks for the simplest living cell to come to existence.
2a. Proteins are highly complex structures that are very difficult for scientists to create.
2b. Which scientists created nature’s proteins which human scientists find so difficult to imitate or recreate.
3a. The probability of random creation of complex proteins, the assemblage of the needed 239 in one place in nature without any control is less than 10^50 or impossible.
3b. A question is also: “Who moves the proteins and the building blocks of the proteins into creating and assembling”.
3c. If you leave all the atoms of such structures in an isolated place nothing will happen. If you make nature’s forces working then we must say that you make the gods working, since no force is ever reported to work without thinking, feeling, willing, which is the work of a person, according to the dictionary.
4. Such impossibility of chance indicates the necessity of an intelligent designer.
5. That expert designer all men call God.
6. God exists.



http://creation.com/origin-of-life



Donald E. Johnson  (Ph.D: Computer & Information Science; Ph.D: Chemistry)

Abstract. The origin of life's biggest mystery is the origin of the genome which contains the information to cybernetically control all aspects of cellular life today. Without formal control, no life would exist. The genetics-first and metabolism-first models will be examined, each having characteristics that strain scientific credibility. Major physical science limitations and the formidable information science problems are examined. These problems usually result in over-simplifications in speculative  scenarios. More serious are the peer-reviewed scientific null  hypotheses that require falsification before any of the naturalistic scenarios can be considered as serious science. Assuming the problems can be resolved, the requirements for a minimal "genome" can be discussed in the areas of initial generation of programmed controls, replication of the genome and needed components that make it useful, regulation of "life's" processes, and evolvability. Life is an intersection of the physical sciences of chemistry and physics and the nonphysical formalism of information science. Each domain must be investigated using that domain's principles. Yet most scientists have been attempting to use physical science to explain life's nonphysical information domain, a practice that has no scientific justification.

Introduction: Pseudo-Scientific Speculations or Science?
 
A hundred years ago, the title's question wouldn't have been needed  since a cell was thought to be bag of plasm  originating in a "warm little pond" . Fifty years ago, protein and DNA structures had been determined so science "knew" the secrets of the genome. With the Miller/Urey synthesis, many thought that the origin of life explanation was near. Fifteen years ago, it started to be realized that "junk DNA" was a misnomer. Five years ago, epigenetic control systems largely determined by non-coding DNA began to be discovered. As new knowledge of functional complexity is revealed, we realize that our knowledge of that complexity has been increasing exponentially, with no end in sight. As one layer is pealed back, a new level of functional complexity is exposed. Rather than getting simpler, the more we know, the more we know we don't know! "As sequencing and other new technologies spew forth data, the complexity of biology has seemed to grow by orders of Magnitude" . There seems to be an exponential increase in knowledge, with the target of understanding the origin receding ever faster. 

The origin of life (OOL) is unknown and is obscured by the lack of  knowledge of the prebiotic conditions that existed as life "developed." "Most of the (bio)chemical processes found within all the living organisms are well understood at the molecular level, whereas the origin of life remains one of the most vexing issues in chemistry, biology, and philosophy". "The origin of life remains one of the humankind's last great unanswered questions, as well as one of the most experimentally challenging research areas" . Any speculation inevitably involves science as we don't know it. It is metaphysically presumed that since life obviously exists, there must have been a time when non-life developed into life through natural mechanisms. It is also presumed (with no substantiating reasons) that Pasteur's Law of Biogenesis, all life is from life ("Omne vivum ex vivo" ), must not have been applicable during life's formation from inanimate material. Pasteur's warning that "Spontaneous generation is a dream" ("La génération spontanée est une chimère"  ) is perhaps appropriate to consider with the various speculations. It is important to realize that "we don't yet know, but the answers will be coming" isn't a scientific statement, but rather expresses faith in naturalism-of-the-gaps, which is no more scientific than the god-of-the-gaps explanation that most scientists would dismiss out-of-hand.

Speculation on a particular aspect of life may not prove fruitful since all known life is a carefully-orchestrated cybernetic system. Without consideration of the origin of cybernetic processes, they are "systems and processes that interact with themselves and produce themselves from themselves". Michael Polanyi argued that life is not reducible to physical and chemical principles, but rather that, "the information content of a biological whole exceeds that of the sum of its parts". "A whole exists when it acts like a whole, when it produces combined effects that the parts cannot produce alone" . "Understanding the origin of life requires knowledge not only of the origin of biological molecules such as amino acids, nucleotides and their polymers, but also the manner in which those molecules are integrated into the organized systems that characterize cellular life"

It should be noted that speculation is important within science, since that is the way that new lines of thought are proposed in order to test scenarios for possibility and feasibility . While the dream of becoming a Nobel laureate may encourage wide dissemination of a speculation, it seems appropriate to warn about spreading such speculations outside the scientific community. The public too often views a scientist's speculation as validated science, so that the speculative nature is overlooked. The public may value a scientist's view in much the same way that a movie star's endorsement of a product is seen as important. There seems to be a wide-spread belief in chemical predestination, even though its chief promoter  has repudiated its possibility. For example, when signs of water on Mars were discovered, the media proclaimed that there must be life then. Our collective preoccupation with the Search for Extraterrestrial  Intelligence illustrates the belief in the inevitability of life.

1. Overview 

The approach of this essay will be to consider scenarios for developing the minimal replication and control information ("proto-genome") for a protocell, since even "protolife" would require self-replication and control ability. Note that the ability to use the "genomic" information for functionality is also critical. Metabolic cycles , homochirality, cell membranes, and other required components will not be the primary thrust, even though all are indirectly controlled by today's genome. An excellent review of the organic chemistry for biomolecular origin is available. Each proponent's scenario will be briefly highlighted, with the primary arguments against the scenario coming from proponents of an alternative scenario, typically as quotes. Finally, we'll examine principles that are almost universally ignored in OOL scenarios, but are in critical need of scientific explanation.


1.1 RNA (Genetics) First Scenarios 

A ribosome, "a molecular fossil", can join amino acids  without additional enzymes except for those that are imbedded in the ribosome itself to make it a ribozyme (enzymes needed to manufacture tRNAs presumably developed later). "An appeal of the RNA world hypothesis is that it solves the 'chicken and egg' problem; it shows that in an earlier, simplified biota the genotype/replicator and pheno- type/catalyst could have been one and the same molecule" (but the RNA/enzyme of a ribozyme is another chicken/egg problem). "RNA appears well suited to have served as the first replicative polymer on this planet". The origin of the RNA World by stringing together optimistic extrapolations of prebiotic chemistry achievements and experimenter-directed RNA "evolution" (a misnomer) has been described as "the 'Molecular Biologists' Dream ... [and] the prebiotic chemist's nightmare". The "difficulties in nucleobase ribosylation can be overcome with directing, blocking, and activating groups on the nucleobase and ribose.  These molecular interventions are synthetically ingenious, but serve to emphasize the enormous difficulties that must be overcome if ribonucleosides are to be efficiently produced by nucleobase ribosylation under prebiotically plausible conditions. This impasse has led many scientists to abandon the idea that a RNA "genome" might have assembled abiotically, and has prompted a search for potential pre-RNA informational molecules" . It has been pointed out that "what is essential, therefore, is a reasonably detailed description, hopefully supported by experimental evidence, of how an evolvable family of cycles might operate. The scheme should not make unreasonable demands on the efficiency and specificity of the various external and internally generated catalysts that are supposed to be involved. Without such a description, acceptance of the possibility of complex non-enzymatic cyclic organizations that are capable of evolution can only be based on faith, a notoriously dangerous route to scientific progress" . The experimenter- directed "side products would have amounted to a fatal and committed step in the synthesis of a nascent proto-RNA. This problem illustrates a difficulty in non-enzymatic polymerization that must be taken into account when considering how the nature of the synthetic routes to and structural identities of early genetic polymers: irreversible linkages are adaptive for an informational polymer only when mechanisms exist to make them conditionally reversible. 

No physical law need be broken for spontaneous RNA formation  to happen, but the chances against it are so immense, that the suggestion implies that the non-living world had an innate desire to generate RNA. There is no reason to presume that an indifferent nature would not  combine units at random, producing an immense variety of hybrid short, terminated chains, rather than the much longer one of uniform backbone geometry needed to support replicator and catalytic functions". "The RNA molecule is too complex, requiring assembly first of the monomeric constituents of RNA, then assembly of strings of monomers into polymers. As a random event without a highly structured chemical context, this sequence has a forbiddingly low probability and the process lacks a plausible chemical explanation, despite considerable effort to supply one"  "It has been challenging to identify possible prebiotic chemistry that might have created RNA. Organic molecules, given energy, have a well-known propensity to form multiple products, sometimes referred to collectively as 'tar' or 'tholin.' These mixtures appear to be unsuited to support Darwinian processes, and certainly have never been observed to spontaneously yield a homochiral genetic polymer. To date, proposed solutions to this challenge either involve too much direct human intervention to satisfy many in the community, or generate molecules that are unreactive 'dead ends' under standard conditions of temperature and pressure".  Some  believe that inorganic crystals or clay served as a  template for the original RNA. The "replication of clay 'information' has remained hypothetical, and transfer of replicated clay properties to  nucleic acids even more so". Crystals contain a very small  quantity of information in their regular structures, so that any significant information would have to be in irregularities. How would inanimate nature produce those irregularities to serve as templates for  functional information in replicative polymers? 
"The reaction system... is a purified reconstituted system in which all of the components and their concentrations are defined. The number of components is amazingly large, yet this is one of the simplest encapsulated systems for carrying out protein translation and RNA replication. With regard to the origin of life, the first living systems would have had functionally identical translation and replication systems, but they must have been simpler and contained machinery for nutrient transport. The complexity of our system implies that extant translation machinery has become highly sophisticated during the evolutionary process" .


1.2 Metabolism-First Scenarios

Metabolism-first scenarios involve development of a self-replicating, self-sustaining chemical system that is able to capture energy and that is contained within a protocell [24] or geothermal vent [38-39]. Perhaps energy transfer used an "osmosis first" paradigm [40, 26]. Unlike RNA first, there is no nucleotide genome to control replication or component construction so that selection would have favored "not the best replicator, but the reaction that sucked in fuel the quickest, denying energy to other chemical processes" [41]. The "bag of chemicals" (composome) presumably would grow until it reaches a size that enables it to divide, with each "daughter" inheriting about half the chemical contents. "The origin of life was marked when a rare few protocells happened to have the ability to capture energy from the environment to initiate catalyzed heterotrophic growth directed by heritable genetic information in the polymers ... The origin of life occurred when a subset of these molecules was captured in a compartment and could interact with one another to produce the properties we associate with the living state" [39]. There have been simulations [42-43] in which the composomes "undergo mutation-like compositional changes" that are claimed to illustrate evolution, but these have never been experimentally observed. 

Although metabolism-first avoids the infeasibility of forming functional RNA by chance, "replication of compositional information is so inaccurate that fitter compositional genomes cannot be maintained by selection and, therefore, the system lacks evolvability (i.e., it cannot substantially depart from the asymptotic steady-state solution already built-in in the dynamical equations). We conclude that this fundamental limitation of ensemble replicators cautions against metabolism-first theories of the origin of life" [44]. Concerning the chemical cycles required, "These are chemically very difficult reactions ... One needs, therefore, to postulate highly specific catalysts for these reactions. It is likely that such catalysts could be constructed by a skilled synthetic chemist, but questionable that they could be found among naturally occurring minerals or prebiotic organic molecules. The lack of a supporting background in chemistry is even more evident in proposals that metabolic cycles can evolve to 'life-like' complexity. The most serious challenge to proponents of metabolic cycle theories—the problems presented by the lack of specificity of most non-enzymatic catalysts—has, in general, not been appreciated. If it has, it has been ignored. Theories of the origin of life based on metabolic cycles cannot be justified by the inadequacy of competing theories: they must stand on their own" [20].


2. Major Unresolved Difficulties 

Nearly all scenarios presented as science during this author's education using the American Chemical Society's "From Molecules to Man" have been shown to be incorrect by today's science. Scientists need to use much caution during speculative dreaming about mechanisms that can be considered as explanations for the observations that are currently available. Some of the major difficulties requiring scientific explanation will be highlighted in this section


2.1 Physical Science Limitations 

What natural interactions produced homochilarity, -linkage only amino acids, and non-enzymatic peptide bonds and other dehydration reactions in aqueous solutions to produce proteins and RNAs? What physical laws could integrate biochemical pathways and cycles into a formal protometabolic scheme? How did the enzymes required to level life's 10^19 range of uncatalyzed reactions [45] spontaneously polymerize and self-assemble?

2.2 Formidable Information Science Problems 
"Biological information is not a substance ... biological information is not identical to genes or to DNA (any more than the words on this page are identical to the printers ink visible to the eye of the reader). Information, whether biological or cultural, is not a part of the world of substance" [46]. "All the equations of physics taken together cannot describe, much less explain, living systems. Indeed, the laws of physics do not even contain any hints regarding cybernetic processes or feedback control" [10]. The argument for abiogenesis "simply says it happened. As such, it is nothing more than blind belief. Science must provide rational theoretical mechanism, empirical support, prediction fulfillment, or some combination of these three. If none of these three are available, science should reconsider that molecular evolution of genetic cybernetics is a proven fact and press forward with new research approaches which are not obvious at this time" [47]. "The challenge for an undirected origin of such a cybernetic complex interacting computer system is the need to demonstrate that the rules, laws, and theories that govern electronic computing systems and information don't apply to the even more complex digital information systems that are in living organisms. Laws of chemistry and physics, which follow exact statistical, thermodynamic, and spatial laws, are totally inade-quate for generating complex functional information or those systems that process that information using prescriptive algorithmic information" [48]. 

It is important to realize that data generated by regular fluctuations  (such as seasons or light/dark cycles) have extremely low information content, offering no explanation for life's functional information. Communication of information requires that both sender and receiver  know the arbitrary protocol determined by rules, not law. A functioning protocell would have needed formal organization, not redundant order. Organization requires control, which requires  formalism as a reality. Each protein is currently the result of the execution of a real computer program running on the genetic operating system. How did inanimate nature write those programs and  operating systems?
The genome would be useless without the  processing systems needed to carry out its prescriptive instructions.

2.3 Over-Simplification of Information Requirements 

"Whatever the source of life (which is scientifically unknowable), the alphabet involved with the origin of life, by the necessary conditions of information theory, had to be at least as symbolically complex as the current codon alphabet. If intermediate alphabets existed (as some have speculated), each predecessor also would be required to be at least as complex as its successor, or Shannon's Channel Capacity [49] would be exceeded for information transfer between the probability space of alphabets with differing Shannon capacity. Therefore, life's original alphabet must have used a coding system at least as symbolically complex as the current codon alphabet. There has been no feasible natural explanation proposed to produce such an alphabet since chance or physicality cannot produce functional information or a coding system, let alone a system as complex as that in life" [50]. Coded information has never been observed to originate from physicality. "Due to the abstract character of function and sign systems [semiotics -- symbols and their meaning], life is not a subsystem of natural laws. This suggests that our reason is limited in respect to solving the problem of the origin of life and that we are left accepting life as an axiom... Life express[es] both function and sign systems, which indicates that it is not a subsystem of the [physical] universe, since chance and necessity cannot explain sign systems, meaning, purpose, and goals" [51]. "The reductionist approach has been to regard information as arising out of matter and energy. Coded information systems such as DNA are regarded as accidental in terms of the origin of life and that these then led to the evolution of all life forms as a process of increasing complexity by natural selection operating on mutations on these first forms of life" [52]. "From the information perspective, the genetic system is a pre-existing operating system of unknown origin that supports the storage and execution of a wide variety of specific genetic programs (the genome applications), each program being stored in DNA. DNA is a storage medium, not a computer, that specifies all information needed to support the growth, metabolism, parts manufacturing, etc. for a specific organism via gene subprograms" [50]. 

There are many features in current life that are extremely difficult to envision as arising from a protocell. The smallest genome (though not autonomous) found so far is in "the psyllid symbiont Carsonella ruddii, which consists of a circular chromosome of 159,662 base pairs... The genome has a high coding density (97%) with many overlapping  genes and reduced gene length" [53]. "The origin and evolution of overlapping genes are still unknown" [54]. Since they are prevalent in the simplest known genome, a big question is how and why did overlapping genes arise? Recently, sub-coded information [55] and a second genetic code [56] characterizing alternative splicing have been discovered. Various transcribed RNAs are mixed and matched and spliced into mRNAs for specifying protein construction and other controls. MicroRNAs regulate large networks of genes by acting as master control switches [57]. Tiny polypeptides (with 11-32 amino acids) can function as "micro-protein" gene expression regulators [58]. Were these features required initially, or by what interactions of nature  did they arise later?  Scientists are investigating "the organization of information in  genomes and the functional roles that non-protein coding RNAs play in the life of the cell. The most significant challenges can be summarized by two points: a) each cell makes hundreds of thousands of different RNAs and a large percent of these are cleaved into shorter functional RNAs demonstrating that each region of the genome is likely to be multifunctional and b) the identification of the functional regions of a genome is difficult because not only are there many of them but because the functional RNAs can be created by taking sequences that are not near each other in the genome and joining them together in an RNA molecule. The order of these sequences that are joined together need not be sequential. The central mystery is what controls the temporal and coordinated expression of these RNAs" [59]. "It is very difficult to wrap your head around how big the genome is and how complicated ... It's very confusing and intimidating ... The coding parts of genes come in pieces, like beads on a string, and by splicing out different beads, or exons, after RNA copies are made, a single gene can potentially code for tens of thousands of different proteins, although the average is about five ... It's the way in which genes are switched on and off, though, that has turned out to be really mind-boggling, with layer after layer of complexity emerging" [60]. When and how did these  features arise? Were any present in the first life? 
2.4 Scientific Hypotheses Requiring Falsification 

In addition to falsifying Shannon Capacity Theorem [49] if a  proposed original information system isn't as complex as today's  codon-based system, the following testable null hypotheses (proposed in peer-reviewed papers) may require falsification. No scenario should be accepted as science if it violates one or more of these unfalsified null hypotheses [60-61, 11-12]. 

Stochastic ensembles of physical units cannot program algorithmic/cybernetic function. 

Dynamically-ordered sequences of individual physical units  (physicality patterned by natural law causation) cannot program algorithmic/cybernetic function.

Statistically weighted means (e.g., increased availability of certain  units in the polymerization environment) giving rise to patterned (compressible) sequences of units cannot program algorithmic/cybernetic function. 

Computationally successful configurable switches cannot be set by  chance, necessity, or any combination of the two, even over large periods of time.
 
Self-ordering phenomena cannot generate cybernetic organization. Randomness cannot generate cybernetic organization. 

PI (prescriptive information [12]) cannot be generated from/by the chance and necessity of inanimate physicodynamics.

PI cannot be generated independent of formal choice contingency. 

Formal algorithmic optimization, and the conceptual organization  that results, cannot be generated independent of PI.


Physicodynamics cannot spontaneously traverse The Cybernetic Cut [11]: physicodynamics alone cannot organize itself into formally functional systems requiring algorithmic optimization computational halting, and circuit integration.

3. Could a Protocell Live and Reproduce Without a "Genome?" 

Assuming that the problems highlighted in the previous sections can be overcome (including falsifications of 2.4), this section will discuss the key topic of this essay. The protocell will be assumed to have an appropriate boundary (membrane, microtubule, etc.) that separates the "living" protocell from its environment. This section  will highlight what would be required of a "proto-genome," without regard as to whether such a "genome" is feasible (not operationally falsified). "There seems to be little general agreement as to how the molecular apparatus needed to implement genetics within a cell could have come about. In fact, there seems to be nothing but puzzlement on such questions with virtually no chemically founded suggestions being made at all" [63]. We will be examining the functional requirements of the proto-genome, as opposed to hypothetical implementations. A proto-genome may have little resemblance to today's DNA-based genome since it will be assumed that life's origin didn't involve DNA. Consequently, we will be attempting to examine life as we don't know it, an exercise that should always be accompanied by healthy scientific skepticism. It is important to realize that John von Neumann proposed and proved the requirements for a self-replicating automaton long before the discovery of DNA's information [64]. A self-reproducing system must contain the necessary components of any computer system, as well as the program for its own construction with the hardware needed to accomplish that construction.


3.1 Replication Requirements 

A mechanism is needed to divide the protocell into two approximately equal daughters with each daughter being capable of growth and eventual division for exponential population potential. The "proto-genome" with its processing system must replicate itself, along with all cellular controls (functional information and senders/receivers/processors) into each daughter. Unless the "proto-genome" has replisome capabilities included in the "proto-genome" rather than a separate enzyme, the self-contained capability is required to duplicate all other needed components for "life" with high fidelity. Each daughter also needs a replicated (or split) cell boundary.
 
Science knows that the current replication hardware and software  requires all the components to be fully functional for replication to occur at all. All known errors during replication result in a decrease of both Shannon and functional information [65], usually producing a cell that is no longer able to reproduce. Reliable replication is fundamental to life, a characteristic lacking in composomes [44].

3.2 Control Requirements 

Controlled chemical metabolic networks are needed that can selectively admit "fuel" (redox, heat, photons, etc.) into the cell and process the "fuel" to harness the energy for growth, reproduction, manufacturing of needed components that can't migrate in, and other useful work.
Both sender and receiver of the each control signal are needed, along with knowledge of the protocol rules for correct  communication. The manufacturing control for needed cellular  components would probably require enzymatic functionality for polymerization, along with producing homochiral components. In addition, control is required for cell division. Without control, organization (as opposed to self-ordering) is impossible, and functionality would disintegrate, with "tar" a likely result. 

Cellular control is a cybernetic process, so all of the requirements  of the first eight chapters need instantiation into the protocell. While the proto-genome may contain the control instructions, those instructions must be read by other components (unless the proto-genome has expanded capabilities so that it can read itself), and communicated reliably (using "agreed upon" arbitrary protocols between sender and receiver, source and destination) to the components effecting the control operations. This is not an easily-dismissed prerequisite since control in known life is critical to make the chemical components "alive." In addition, mere physicodynamic constraints cannot generate formal biological controls [66].

3.3 Evolvability Requirements 

The system would have to be capable of accurate duplication, but capable of gradual changes that would permit evolution to life-as-we-know-it. A robust information structure that can be self-maintained (including error-correction), such as in a long genetic polymer, would be required. The feasibility of formation of such a polymer has yet to be shown with any prebiotic mixture proposed to  date. The enzyme- and template-independent 120-mer polymers  recently generated in water at high temperatures [67] are non-informational homopolymers similar to those adsorbed onto montmorillonite clay surfaces [68]. The aqueous polymers are also cyclic and require some experimenter engineering to achieve 120 mer length.

The proto-genome would also need to be able to effect highly accurate duplication of the entire proto-cell, with only an occasional "error" that could produce a very similar proto-cell, still possessing all three of the requirements in section 3. The proto-genome, along with all the proto-cell components, would need to have a feasible path to eventually produce cells with the functional complexity of today's life. It does little good to speculate a "simple" initial system unless there are feasible scenarios that can traverse from the proposed initial system to life as we know it, including coded information and other features highlighted previously. For example, one could envision dipping a finger into a bottle of ink and flicking the ink toward a white sheet would eventually produce a pattern that looks like an English letter. That would not explain the formal rules and meaningful syntax of letters that you are currently observing in this book, however.

4. Conclusions 
While scenarios for the first cell can be envisioned purely from  physicality, a "proto-genome" introduces cybernetic aspects that can have no origination from inanimate material. In particular, organization, prescriptive information, and control require traversing The Cybernetic Cut on a one-way CS (Configurable Switch) Bridge [11] that allows traffic only from formalism to physicality. Just as formalism needs recognition as reality, it is also critical to recognize the limits of physical science, such as physics and chemistry, whose spontaneous inanimate mass/energy interaction behavior is constrained by laws, not formal controls. Initial starting constraints chosen by an experimenter become controls for an experiment, but those chosen constraints are instantiations into physicality of nonphysical formalisms. Life is an intersection of physical science and information science.  Both domains are critical for any life to exist, and each must be investigated using that domain's principles. Yet most scientists have been attempting to use physical science to explain life's information domain, a practice that has no scientific justification. Since the chemistry and physics of life are controlled by prescriptive information (not just constrained by laws), biology is really an information science, not a physical science.

1) http://www.asa3.org/ASA/education/origins/ic-cr.htm



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One Way To Think About the Complexity of the “Simplest” Life Form 1

I have always been fascinated by the question, “How simple can life get?” After all, anything that is alive has to perform certain functions such as reacting to external stimuli, taking in energy and converting that energy to its own use, reproducing, etc. Exactly how simple can a living system be if it has to perform such tasks? Many biologists have investigated this question, but there isn’t a firm answer. Typically, biologists talk about how simple a genome can be. The simplest genome belongs to a bacterium known as Carsonella ruddii. It has 159,662 base pairs in its genome, which is thought to contain 182 genes.1 However, it is not considered a real living organism, as it cannot perform all the functions of life without the help of cells found in jumping plant lice.


The bacterium known as Pelagibacter ubique has the smallest genome of any truly free-living organism. It weighs in at 1,308,759 base pairs and 1,354 genes.2 However, there is something in between these two bacteria that might qualify as a real living organism. It is the bacterium Mycoplasma genitalium. It’s genome has 582,970 base pairs and 525 genes.3 While it is a parasite, it performs all the standard functions of life on its own. It just uses other organisms (people as well as animals of the order Primates) for food and housing. Thus, while it cannot exist without other organisms, it might be the best indicator of how “simple” life can get.

If you follow science news at all, you might recognize the name. Two years ago, Dr Craig Venter and his team constructed their own version of that bacterium with the help of living versions of the bacterium, yeast cells, and bacteria of another species from the same genus. Well, now a scientist from Venter’s lab teamed up with several scientists from Stanford University to produce a computer simulation of the bacterium!

Their work, which seems truly marvelous, gives us deep insight into how complex the “simplest” living organism really is.


Let’s start with what the computer simulation actually accomplished. It modeled all the inputs and outputs of the bacterium’s 525 genes throughout a single cell cycle. In other words, it simulated how the genome produces proteins, how those proteins interact with other proteins, and how the entire system is regulated. It followed these processes through all the events leading up to and including the cell reproducing itself.4

Now that’s a lot of work! How did the authors do it? Well, they looked at over 900 different scientific papers that had been produced on the inner workings of Mycoplasma genitalium, and they identified 1,900 specific parameters that seem to govern how the cell operates. There were several discrepancies that were found among the papers involved, and as a result, there was a lot of reconciliation that had to be done. The details of this reconciliation and other matters are found in a 120-page supplement to the 12-page scientific paper.

Once the reconciliation of these studies was accomplished, the essential workings of the cell were split into 28 separate modules that each governed specific functions of the cell. For example, one module dealt with metabolism, while another dealt with the activation of proteins once they were produced. Once each module was built and tested individually, the modules were then joined by looking at what they produced every second. If the products of one module were the kinds of chemicals used by a second module, those products were then treated as inputs to the second module for the next second of computation. The computation proceeded like this (checking the inputs and outputs of each module) for about 10 hours, which is roughly the time it takes a real Mycoplasma genitalium to reproduce.

Why would a group want to undertake such a complex endeavor? Well, one obvious reason is the reconciliation that I mentioned previously. As independent papers, each of the 900 studies to which the authors referred made sense. However, when the authors started using the results of those studies in a model that tries to take all the molecular processes of a cell into account, they found that some results didn’t mesh well with others. The reconciliation that had to take place to get the simulation working will help us better understand the limits of many of the studies related to Mycoplasma genitalium and hopefully will lead to more detailed studies that will slowly wipe away such discrepancies. Also, as the authors state, these kinds of models will:

…accelerate biological discovery and bioengineering by facilitating experimental design and interpretation. Morever, [this study and others] raise the exciting possibility of using whole-cell models to enable computer-aided rational design of novel microorganisms.

So in the end, not only will such models help us better design and interpret experiments, they might one day lead us to ways that we can engineer new microorganisms.

This is fantastic work, and I do think it opens up new vistas in cell and molecular biology. However, we need to pull back for a moment and think about the direct implications of this computer simulation. It simulated, in very basic terms, the molecular interactions that occur in a cell that might be a good analog for the simplest possible life form. It skipped over a lot of details, of course, so it is not a complete simulation by any means. Nevertheless, it is a great first step towards understanding how a living system really works.

Now let’s look at this in very practical terms. In order to be able to match the speed at which the organism operates, this less-than-complete simulation required a cluster of 128 computers to get the job done. Think about that for a moment. In order to simulate most (but not all) of the processes that take place in an analog for what might be the simplest possible living organism, the authors needed the power of 128 computers running together! That should tell us something very clearly:

There is no such thing as a simple living organism.
The more we understand life, the more clear it becomes that even the “simplest” version of it has to be the result of design.

REFERENCES

1. Atsushi Nakabachi, et al., “The 160-Kilobase Genome of the Bacterial Endosymbiont Carsonella,” Science 314:267, 2006.
Return to Text

2. Stephen J. Giovannoni, et al., “Genome Streamlining in a Cosmopolitan Oceanic Bacterium,” Science 309:1242-1245, 2005.
Return to Text

3. According to the Comprehensive Microbial Resource Manual.
Return to Text

4. Jonathan R. Karr, et al., “A Whole-Cell Computational Model Predicts Phenotype from Genotype,” Cell 150(2):389-401, 2012.
Return to Text

1) http://blog.drwile.com/?p=8161



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http://www.uncommondescent.com/intelligent-design/both-genetics-first-and-metabolism-first-origin-of-life-models%E2%80%9D-strain-scientific-credibility-%E2%80%9D/

The Stanford investigators determined that the essential genome of C. crescentus consisted of just over 492,000 base pairs (genetic letters), which is close to 12 percent of the overall genome size. About 480 genes comprise the essential genome, along with nearly 800 sequence elements that play a role in gene regulation.,,, When the researchers compared the C. crescentus essential genome to other essential genomes, they discovered a limited match. For example, 320 genes of this microbe’s basic genome are found in the bacterium E. coli. Yet, of these genes, over one-third are nonessential for E. coli. This finding means that a gene is not intrinsically essential. Instead, it’s the presence or absence of other genes in the genome that determine whether or not a gene is essential.

Jack T. Trevors – Theoretical Biology & Medical Modelling, Vol. 2, 11 August 2005, page 8 1
“No man-made program comes close to the technical brilliance of even Mycoplasmal genetic algorithms. Mycoplasmas are the simplest known organism with the smallest known genome, to date. How was its genome and other living organisms’ genomes programmed?”

The Archaea and Bacteria share a large number of metabolic genes that are not found in eukaryotes. If these two “prokaryotic” groups span the primary phylogenetic divide and their genes are vertically (genealogically) inherited, then the universal ancestor must have had all of these genes, these many functions. This distribution of genes would make the ancestor a prototroph with a complete tricarboxylic acid cycle, polysaccharide metabolism, both sulfur oxidation and reduction, and nitrogen fixation; it was motile by means of flagella; it had a regulated cell cycle, and more. This is not the simple ancestor, limited in metabolic capabilities, that biologists originally intuited. That ancestor can explain neither this broad distribution of diverse metabolic functions nor the early origin of autotrophy implied by this distribution. The ancestor that this broad spread of metabolic genes demands is totipotent , a genetically rich and complex entity, as rich and complex as any modern cell—seemingly more so.



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http://spectrummagazine.org/article/book-reviews/2009/10/06/signature-cell

According to Meyer the “simplest extant cell, Mycoplasma genitalium — a tiny bacterium that inhabits the human urinary tract — requires ‘only’ 482 proteins to perform its necessary functions….” If, for the sake of argument, we assume the existence of the 20 biologically occurring amino acids, which form the building blocks for proteins, the amino acids have to congregate in a definite specified sequence in order to make something that “works.” First of all they have to form a “peptide” bond and this seems to only happen about half the time in experiments. Thus, the probability of building a chain of 150 amino acids containing only peptide links is about one chance in 10 to the 45th power.

In addition, another requirement for living things is that the amino acids must be the “left-handed” version. But in “abiotic amino-acid production” the right- and left-handed versions are equally created. Thus, to have only left-handed, only peptide bonds between amino acids in a chain of 150 would be about one chance in 10 to the 90th. Moreover, in order to create a functioning protein the “amino acids, like letters in a meaningful sentence, must link up in functionally specified sequential arrangements.” It turns out that the probability for this is about one in 10 to the 74th. Thus, the probability of one functional protein of 150 amino acids forming by random chance is 10 to the 164th. If we assume some minimally complex cell requires 250 different proteins then the probability of this arrangement happening purely by chance is one in 10 to the 164th multiplied by itself 250 times or one in 10 to the 41,000th power.

there are about 10 to the 80th elementary particles in our observable universe. Assuming a Big Bang about 13 billion years ago, there have been about 10 to the 16th seconds of time. Finally, if we take the time required for light to travel one Plank length we will have found “the shortest time in which any physical effect can occur.” This turns out to be 10 to the minus 43rd seconds. Or turning it around we can say that the most interactions possible in a second is 10 to the 43rd. Thus, the “probabilistic resources” of the universe would be to multiply the total number of seconds by the total number of interactions per second by the total number of particles theoretically interacting. The math turns out to be 10 to the 139th.

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Determination of the Core of a Minimal Bacterial Gene Set 1




http://reasonandscience.heavenforum.org/t2110-what-might-be-a-protocells-minimal-requirement-of-parts#3797

Proteins are essential building blocks of living cells; indeed, life can be viewed as resulting substantially from the chemical activity of proteins. Because of their importance, it is hardly surprising that ancestors for most proteins observed today were already present at the time of the 'last common ancestor', a primordial organism from which all life on Earth is descended. How did the first proteins arise? How can we bring a taxonomic order to the diversity of forms that evolved from them? These two questions are at the center of our scientific efforts, on which we bring to bear methods in bioinformatics, protein biochemistry and structural biology.

Based on the conjoint analysis of several computational and experimental strategies designed to define the minimal set of protein-coding genes that are necessary to maintain a functional bacterial cell, we propose a minimal gene set composed of 206 genes. Such a gene set will be able to sustain the main
vital functions of a hypothetical simplest bacterial cell with the following features.

(i) A virtually complete DNA replication machinery, composed of one nucleoid DNA binding protein, SSB, DNA helicase, primase, gyrase, polymerase III, and ligase. No initiation and recruiting proteins seem to be essential, and the DNA gyrase is the only topoisomerase included, which should perform
both replication and chromosome segregation functions.

(ii) A very rudimentary system for DNA repair, including only one endonuclease, one exonuclease, and a uracyl-DNA glycosylase.

(iii) A virtually complete transcriptional machinery, including the three subunits of the RNA polymerase, a  factor, an RNA helicase, and four transcriptional factors (with elongation, antitermination, and transcription-translation coupling functions). Regulation of transcription does not appear to be essential in bacteria with reduced genomes, and therefore the minimal gene set does not contain any transcriptional regulators.

(iv) A nearly complete translational system. It contains the 20 aminoacyl-tRNA synthases, a methionyl-tRNA formyltransferase, five enzymes involved in tRNA maturation and modification, 50 ribosomal proteins (31 proteins for the large ribosomal subunit and 19 proteins for the small one), six proteins necessary for ribosome function and maturation (four of which are GTP binding proteins whose specific function is not well known), 12 translation factors, and 2 RNases involved in RNA degradation.

(v) Protein-processing, -folding, secretion, and degradation functions are performed by at least three proteins for posttranslational modification, two molecular chaperone systems (GroEL/S and DnaK/DnaJ/GrpE), six components of the translocase machinery (including the signal recognition particle, its receptor, the three essential components of the translocase channel, and a signal peptidase), one endopeptidase, and two proteases.

(vi) Cell division can be driven by FtsZ only, considering that, in a protected environment, the cell wall might not be necessary for cellular structure.

(vii) A basic substrate transport machinery cannot be clearly defined, based on our current knowledge. Although it appears that several cation and ABC transporters are always present in all analyzed bacteria, we have included in the minimal set only a PTS for glucose transport and a phosphate transporter. Further analysis should be performed to define a more complete set of transporters.

(viii) The energetic metabolism is based on ATP synthesis by glycolytic substrate-level phosphorylation.

(ix) The nonoxidative branch of the pentose pathway contains three enzymes (ribulose-phosphate epimerase, ribosephosphate isomerase, and transketolase), allowing the synthesis of pentoses (PRPP) from trioses or hexoses.

(x) No biosynthetic pathways for amino acids, since we suppose that they can be provided by the environment.

(xi) Lipid biosynthesis is reduced to the biosynthesis of phosphatidylethanolamine from the glycolytic intermediate dihydroxyacetone phosphate and activated fatty acids provided by the environment.

(xii) Nucleotide biosynthesis proceeds through the salvage pathways, from PRPP and the free bases adenine, guanine, and uracil, which are obtained from the environment.

(xiii) Most cofactor precursors (i.e., vitamins) are provided by the environment. Our proposed minimal cell performs only the steps for the syntheses of the strictly necessary coenzymes tetrahydrofolate, NAD, flavin aderine dinucleotide, thiamine diphosphate, pyridoxal phosphate, and CoA.



1) http://mmbr.asm.org/content/68/3/518.full.pdf
http://www.ncbi.nlm.nih.gov/books/NBK2227/
2) http://www.eb.tuebingen.mpg.de/research/departments/protein-evolution.html



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Essential genes of a minimal bacterium 1



Metabolic pathways and substrate transport mechanisms encoded by M. genitalium. Metabolic products are colored red, and mycoplasma proteins are black. White letters on black boxes mark nonessential functions or proteins based on our current gene disruption study. Question marks denote enzymes or transporters not identified that would be necessary to complete pathways, and those missing enzyme and transporter names are colored green. Transporters are colored according to their substrates: yellow, cations; green, anions and amino acids; orange, carbohydrates; purple, multidrug and metabolic end product efflux. The arrows indicate the predicted direction of substrate transport. The ABC type transporters are drawn as follows: rectangle, substrate-binding protein; diamonds, membrane-spanning permeases; circles, ATP-binding subunits.


1) http://www.pnas.org/content/103/2/425/F3.expansion.html

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A Whole-Cell Computational Model Predicts Phenotype from Genotype 1

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A Whole-Cell Computational Model Predicts Phenotype from Genotype 1



M. genitalium Whole-Cell Model Integrates 28 Submodels of Diverse Cellular Processes
(A) Diagram schematically depicts the 28 submodels as colored words—grouped by category as metabolic (orange), RNA (green), protein (blue), and DNA (red)—in the context of a single M. genitalium cell with its characteristic flask-like shape. Submodels are connected through common metabolites, RNA, protein, and the chromosome, which are depicted as orange, green, blue, and red arrows, respectively.
(B) The model integrates cellular function submodels through 16 cell variables. First, simulations are randomly initialized to the beginning of the cell cycle (left gray arrow). Next, for each 1 s time step (dark black arrows), the submodels retrieve the current values of the cellular variables, calculate their contributions to the temporal evolution of the cell variables, and update the values of the cellular variables. This is repeated thousands of times during the course of each simulation. For clarity, cell functions and variables are grouped into five physiologic categories: DNA (red), RNA (green), protein (blue), metabolite (orange), and other (black). Colored lines between the variables and submodels indicate the cell variables predicted by each submodel. The number of genes associated with each submodel is indicated in parentheses. Finally, simulations are terminated upon cell division when the septum diameter equals zero (right gray arrow).



1) http://www.sciencedirect.com/science/article/pii/S0092867412007763

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In order to make life, and specially multicellular complex life,  the building blocks of life, cells, have to be made, which are the tiniest living entities. To build  cells requires information and programming, complex protein manufacturing machines and assembly lines, energy, nutrient supply chains, quality control , waste bins, ability to adapt  to the environment and to react to stimuli, ability of replicating, and housing ( the cell membrane ).

“The complexity of the simplest known type of cell is so great that it is impossible to accept that such an object could have been thrown together suddenly by some kind of freakish, vastly improbable, event. Such an occurrence would be indistinguishable from a miracle.”
― Michael Denton, Evolution: A Theory In Crisis

A primitive cell like an E. coli bacteria - one of the simplest life forms in existence today -- is amazingly complex.

Following the E. coli model, a cell would have to contain at an absolute minimum:

A cell wall of some sort to contain the cell
A genetic blueprint for the cell (in the form of DNA)
DNA polymerase  capable of copying information out of the genetic blueprint to manufacture new proteins and enzymes
Ribosomes capable of manufacturing new enzymes, along with all of the building blocks for those enzymes
An enzyme that can build cell walls
An enzyme able to copy the genetic material in preparation for cell splitting (reproduction)
An enzyme or enzymes able to take care of all of the other operations of splitting one cell into two to implement reproduction (For example, something has to get the second copy of the genetic material separated from the first, and then the cell wall has to split and seal over in the two new cells.)
Enzymes able to manufacture energy molecules to power all of the previously mentioned enzymes   18


The cell compares to a factory :

The Cell membrane separates the interior of all cells from the outside environment. Thats the exterior  factory wall  that protects the factory.

The Nucleus is the  Chief Executive Officer (CEO). It controls all cell activity; determines what proteins will be made and controls all cell activity.

Plasma membrane gates regulate what enters and leaves the cell; where cells makes contact with the external environment. That's the Shipping/Receiving Department. It functions also as the communications department because it is where the cell contacts the external environment.

The Cytoplasm includes everything between the cell membrane and the nucleus. It contains various kinds of cell structures and is the site of most cell activity. The cytoplasm is similar to the factory floor where most of the products are assembled, finished, and shipped.

Mitochondria/chloroplasts: The power plant. Transforms one form of energy into another

Mitochondrial membranes  keep protein assembly lines together for efficient energy production.

Membrane-enclosed vesicles form packages for cargo so that they may quickly and efficiently reach their destinations.

Internal membranes divide the cell into specialized compartments, each carrying out a specific function inside the cell. That are the compartments in a manufacturing facility.

The cytoplasm is contains the organelles; site of most cell activity.  Its like the space inside the factory.

The Endoplasmic Reticulum (ER) is the compartment where the  Assembly lines reside.  (where workers do their work)

The Golgi apparatus: What happens to all the products that are built on the assembly line of a factory? The final touches are put on them in the finishing and packing department. Workers in this part of the plant are responsible for making minor adjustments to the finished products.

Ribosomes build the proteins , equal to  the Workers in the assembly line.

Signal-Recognition Particles (SRP) and signal receptors provide variety of instructions informing the cell as to what destination and pathway the protein must follow. Thats the address on the parcel where it has to be delivered.

Kinesin Motors: Are the cargo carriers in the cell. That are the  forklift carriers in a factory.

Microtubules: They provide platforms for intracellular transport , amongst other things. That are the internal factory highways.

Lysosomes: are capable of breaking down virtually all kinds of biomolecules, including proteins, nucleic acids, carbohydrates, lipids, and cellular debris. Thats the maintainance crew.  It gets rid of the trash, and to dismantle and dispose of the outmoded machinery.

Hormones: permit the communication between the cells. Thats the cellphone to cellphone communication.


while on the other side, inside of cells:


Highest organisation, order, and efficiency in all manufacturing stages and processes
Highest information storage capacity in the nucleus
Highest possible storage density down to atomic scale. DNA can store in 1 gramm  the information of  570 billion 8mb pendrives!
DNA as a storage medium permits to store the data uncorrupted for centuries.
DNA is volumetric (beaker) rather than planar (hard disk)
high economic,  effective and proper material flow inside the cell
maximal  flexibility  for demand and supply fluctuation
simple material delivery routes and pathways throughout the cell that connect the various internal and external parts
flexbility to external  changes and stimuly, since volumes and demand are variable
High efficiency in the regulation of cell size and growth
lowest energy consumption
high efficiency of braking down waste in the cell and reutilisation and reciclying
Unmatched energy efficiency, approximately 10,000 times more energy-efficient than any nanoscale digital transistor
highest adaptability of the manufacturing process to external changes and pressures
fast fix of damage of broken parts

highest complexity " products "
fidelity in reproduction and replication ( exact copies )
highest adaptability of the products to the environment
complete reproduction autonomy without continuing intelligence input
high efficiency signaling systems and communication pathways
high efficiency

Cell's incorporate the highest possible production efficiency , far beyond imagination. Many life forms are unicellular. But the most complex organisms are multi cellular. One stem cell stores the information to make a body consisting of a vast of array of specialized cells, all interlocked , connected and interdependent producing  a harmonic whole, each cell exercising its specific function, producing a goal directed adult, able to reproduce, and adapt to the environment. So life goes on for thousands of years, without direct intelligent intervention.

Its a very complex integrated system with hierarchical layers of regulation and gene expression, similar to the programs and sub-programs of computer software but much more sophisticated. You can imagine a simple evolutionary pathway, but when you get down to the details, it's far from simple. Each embryo follows a precisely choreographed developmental road map in order to get to the final goal -- the reproductive adult.  Each step is necessary but not sufficient by itself. Turn aside from this developmental pathway and the result is likely to be a damaged worm or a dead one. Skip some steps and the same is true. How did this process come about? We would say this goal-directedness is evidence for a designer who had the final end in mind, and arranged the proper developmental steps appropriately.17

Evolutionary biologists disagree. They say this exquisitely refined developmental pathway evolved gradually, a little at a time. First there was a cell, then a eukaryotic cell, one with a nucleus, organelles, and a cytoskeleton. Then along came multicellularity -- cells living together to make an organism, with some cells set aside to make the next generation, and others free to specialize. As time went on, new digestive, muscle, nerve, and sensory cells evolved and were successfully coordinated into functioning whole organisms.

New genes and proteins must be invented. The cytoskeleton, Hox genes, desmosomes, cell adhesion molecules, growth factors, microtubules, microfilaments, neurotransmitters, whatever it takes to get cells to stick together, form different shapes, specialize, and communicate must all come from somewhere.Regulatory proteins and RNAs must be made to control the expression in time and space of these new proteins so that they all work together with existing pathways.In fact, in order for development to proceed in any organism, a whole cascade of coordinated genetic and biochemical events is necessary so that cells divide, change shape, migrate, and finally differentiate into many cell types, all in the right sequence at the right time and place. These cascades and the resulting cell divisions, shape changes, etc., are mutually interdependent. Interrupting one disrupts the others.



Their product is the replicate itself.  producing a new daughter cell. Its as if we

There is no known compelling mechanism of transition from unicellular to multicellular life. In a multicell organism, stem cells know how to replicate and produce all the specialized daughter cells with amazing efficiency, when to produce them, where they belong, and how to deliver them at the right place. So a organism with just two cells, is already perfect in regard of organisation, complexity, build-up correctness in its developing stage, in the same manner as a organism fully grown, as a human with 3 trillion cells.  There is another interesting aspect. Living beings are always finished and fully apt for survival ( unless sudden violent or sometimes slow habitat changes happen, to which the organism cannot react fast enough ).  A child , 10 years old, has a body with all its members and capable faculties, even if not fully grown. Human artifacts are only finished, when fully build, but during the manufacturing process, unfinished, and unusable. So the whole process of growth of the biological organism is consummate and perfect, even if not finished, while human's artifacts are  not.


The major conceptual flaw of naturalistic evolution models is the fact that it builds on a foundation that cannot be backed up rationally. Its a  fact that  major gaps of understanding about  how first cells could have arised, exist. Fantastic scenarios are hypothesized, like naturally arising, three-dimensional compartmentations observed within fossilized seepage-site metal sulphide to explain the arise of the first cell membranes, self replicating RNA strands, precipitates coevolution of dozens of varios cell components at the same time, " quantum evolution ", ideas which do have no scientific backing, but are just scenarios of scientific fiction in the fertile mind of naturalists.  In the same way as the foundation of a building must be ready, in order to build the house, so with the ToE. Despite a division is made, both , abiogenesis, and biodiversity through ToE stand and fall together. If one isn't true, the other most probably isn't either. There is no reason to evoke the idea that a creator used evolution and natural selection to create all biodiversity. Not only, because in my view  that would diminish his glory. And a capable and powerful God, that creates the universe, should also be able to specially create the incredibly various kinds of animals and plants. But principally, because the overal concept and layout of biological machines indicate that there must be planning in the forefront, conceptualisation of the whole process, visualisation of interdependent parts which work as a interlocking whole like machines designed and engeneered my man. Beside the empirical tests , which show that evolution isnt able to produce new functions for enzymes and proteins 19

The final product of the cell is the fidel copy of itself through replication. While human made factories produce things different than itself, the cell as final product makes a copy of itself. When it divides into two, one daughter cell goes on to make a more specialized type of cell, or even gives rise to several different cell types. Multicellular organisms are more complex than unicellular organisms.


Important considerations for a high economic,  effective and proper material flow are required and must be considered, thought and brought in when planning the concepts and layout design of a new factory assembly line, as for example maximal  flexibility in the line for demand and supply fluctuation,  planning  deep enough to answer all possible aspects of a new line to get max efficiency afterwards.   There should be simple material delivery routes and pathways throughout the facility that connect the processes. Also, there needs to be a plan for flexbility and changes, since volumes and demand are variable. Awareness of the many factors involved right in the planning process of the factory is key. Right-sized equipment and facilities must be planned and considered as well. All equipment and facilities should be designed to the demand rate or takt time.  Projects and facility designs  that do not take these considerations in account,  start out great, but quickly bog down in unresolved issues, lack of consensus, confusion and delay.  

 if we look at human assembly lines, the more they are automated, the less new and continuous external information input is required, and exponentially more complex is the required programming in order to make process flow happen automatically. The most sophisticated factory plants of man still require hudge amounts of human workforce constantly. Thats the best we have been able to come up with in a hundred years. The future will be towards more and more automation and robotics, and less and less direct human intelligence and intervention will be required. Cars will drive by their own to destination. Just program and inform the address in the beginning. In a scale of zero to hundred. But cells do every metabolic actions FULLY automated. If there would be a scale: no automation, and simple manufacturing processes made by hand would be 0, and full automation would be 100, the cell would be 100. At the utmost highest rank top position in regard of automation and complexity. And so in regard of storage capacity.

As a paper in Nature Reviews Molecular Cell Biology states, “Today biology is revealing the importance of ‘molecular machines’ and of other highly organized molecular structures that carry out the complex physico-chemical processes on which life is based.” Likewise, a paper in Nature Methods observed that “[m]ost cellular functions are executed by protein complexes, acting like molecular machines.”
Cells and their  metabolic pathways, comparable to fully automated assembly line in factories, are far far more advanced, complex,  better structured and organized in every aspect, than the most advanced robotic assembly facility ever created by man. 16

“Can all of life be fit into Darwin’s theory of evolution?,” and answered: "The complexity of life's foundation has paralyzed science's attempt to account for it; molecular machines raise an as-yet impenetrable barrier to Darwinism's universal reach."

In 1998, former president of the U.S. National Academy of Sciences Bruce Alberts wrote the introductory article to an issue of Cell, one of the world’s top biology journals, celebrating molecular machines. Alberts praised the “speed,” “elegance,” “sophistication,” and “highly organized activity” of “remarkable” and “marvelous” structures inside the cell. He went on to explain what inspired such words:

The entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines. . . . Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts.

A few years later, a review article in the journal Biological Chemistry demonstrated the difficulty evolutionary scientists have faced when trying to understand molecular machines. Essentially, they must deny their scientific intuitions when trying to grapple with the complexity of the fact that biological structures appear engineered to the schematics of blueprints:

Molecular machines, although it may often seem so, are not made with a blueprint at hand. Yet, biochemists and molecular biologists (and many scientists of other disciplines) are used to thinking as an engineer, more precisely a reverse engineer. But there are no blueprints … ‘Nothing in biology makes sense except in the light of evolution’: we know that Dobzhansky (1973) must be right. But our mind, despite being a product of tinkering itself strangely wants us to think like engineers.


Denton, p. 329.
We would see [in cells] that nearly every feature of our own advanced machines had its analogue in the cell: artificial languages and their decoding systems, memory banks for information storage and retrieval, elegant control systems regulating the automated assembly of parts and components, error fail-safe and proof-reading devices utilized for quality control, assembly processes involving the principle of prefabrication and modular construction. In fact, so deep would be the feeling of deja-vu, so persuasive the analogy, that much of the terminology we would use to describe this fascinating molecular reality would be borrowed from the world of late twentieth-century technology.
  “What we would be witnessing would be an object resembling an immense automated factory, a factory larger than a city and carrying out almost as many unique functions as all the manufacturing activities of man on earth. However, it would be a factory which would have one capacity not equalled in any of our own most advanced machines, for it would be capable of replicating its entire structure within a matter of a few hours. To witness such an act at a magnification of one thousand million times would be an awe-inspiring spectacle.”


― Michael Denton, Evolution: A Theory In Crisis
To grasp the reality of life as it has been revealed by molecular biology, we must magnify a cell a thousand million times until it is twenty kilometers in diameter and resembles a giant airship large enough to cover a great city like London or New York. What we would then see would be an object of unparalleled complexity and adaptive design. On the surface of the cell we would see millions of openings, like the port holes of a vast space ship, opening and closing to allow a continual stream of materials to flow in and out. If we were to enter one of these openings we would find ourselves in a world of supreme technology and bewildering complexity.

Unmatched energy efficiency of the cell
A single cell in the human body is approximately 10,000 times more energy-efficient than any nanoscale digital transistor, the fundamental building block of electronic chips. In one second, a cell performs about 10 million energy-consuming chemical reactions, which altogether require about one picowatt (one millionth millionth of a watt) of power.


In contrast to most man-made factories, cells continually dismantle and reassemble their machines at different stages of the cell cycle and in response to environmental challenges, such as infections. Cells use a mixed strategy of prefabricating core elements of machines and then synthesizing additional, snap-on molecules that give each machine a precise function. That provides an economic way to diversify biological processes and also to control them." Thus if the cell needs to respond quickly, such as in a disease or another emergency, it may only need to produce few parts to switch on or tune the machine. On the other hand, if something shouldn't happen, it may only need to block the production of a few molecules. Patrick Aloy and Rob Russell at EMBL used sophisticated computer techniques to reveal the modular organisation of these cellular machines.


The cell is the most complex system mankind has ever confronted. Today we know that the cell contains power stations producing the energy to be used by the cell, factories manufacturing the enzymes and hormones essential for life, a databank where all the necessary information about all products to be produced is recorded, complex transportation systems and pipelines for carrying raw materials and products from one place to another, advanced laboratories and refineries for breaking down external raw materials into their useable parts, and specialized cell membrane proteins to control the incoming and outgoing materials. And these constitute only a small part of this incredibly complex system.

Cellular transport systems:Gated transport is called thus due to it's similarity to our everyday experience of passing through a guarded (electronically or otherwise) gate. This system require three basic components to work: an identification tag, a scanner (to verify identification) and a gate (that is activated by the scanner). The system needs all three components to work otherwise it will not work. Thus in a cell, when a protein is to be manufactured, one of the first steps is for the mRNA [c] to be transported out from the nucleus into the cytoplasm. This requires gated transport of the mRNA at the nuclear pore. Proteins in the pore reads a signal from the RNA (the scanner reads the identification tag) and opens the pore (gate is opened).

The only reason that DNA functions as well as it does is that cells come equipped with an amazing array of cooperative DNA repair mechanisms. For example, polymerase replication during cell division might produce 6 million errors per cell, but then proofreading machinery can reduce this to 10,000 and then mis-match repair machinery could reduce this to 100.  

Question: How could this enormously efficient repair mechanism have evolved, which finds its analogy in our Computer Programs for Spelling Correction ?

So what are the answers in mainstream science literature in regard of the Origin and evolution of metabolic pathways ?

http://flipper.diff.org/app/pathways/info/3461
How the major metabolic pathways actually originated is still an open question.

nice admittance !!


but several different theories have been suggested to account for the establishment of metabolic routes, as The Retrograde hypothesis (Horowitz, 1945), The Granick hypothesis, The Patchwork hypothesis (Ycas, 1974; Jensen, 1976), Semienzymatic origin of metabolic pathways (Lazcano and Miller,1996), The bioinformatic approach , The directed evolution experiments All these ideas are based on gene duplication.

http://onlinelibrary.wiley.com/doi/10.1002/cplx.20365/abstract
Is gene duplication a viable explanation for the origination of biological information and complexity?
Although the process of gene duplication and subsequent random mutation has certainly contributed to the size and diversity of the genome, it is alone insufficient in explaining the origination of the highly complex information pertinent to the essential functioning of living organisms.  8


If a certain line of reasoning  is not persuasive or convincing, then why do atheists not change their mind because of it? The more evolution papers are published, the less likely the scenario of gene duplication ( even questioned by peer reviewed papers, as shown above ) , mutation, and natural selection becomes.  We should consider the fact that modern biology scientific research  may have reached its limits on several key subjects, to which biosynthesis pathways belong. All discussions on principal theories and experiments in the field either end in vague suppositions and guesswork, statements of blind faith, made up scenarios,  or in a confession of ignorance.  Fact is  there remains a huge gulf in our understanding. This lack of understanding is not just ignorance about some technical details; it is a big conceptual gap.  The reach of the end of the road is evident in regard of many, if not almost all major questions. The big questions of macro  evolutionary changes and abiogenesis  are very far from being clearly formulated, even understood,  and nowhere near being solved, and for most, there is no solution at all at sight. But proponents of evolution firmly believe, one day a solution will be found. Not only that, but it seems, the ones that less understand the subject, the more they believe to have the right answers and philosophical position, almost like religious fundamentalists.  Istn't that a prima facie of a " evolution of the gap" position ? We don't know yet, but evolution  and naturalism must be true anyway ? So, the God hypothesis remains out of the equation as a real possibility  in the beginning, and so  at the end, and never receives a serious and honest consideration. If the scientific evidence does not lead towards naturalism providing sactisfactory explanations, why should we not change your minds and look somewhere else ?

15) http://alumnus.caltech.edu/~raj/writing/mass-craft.html
16) http://www.discovery.org/a/14791
17) http://www.evolutionnews.org/2015/04/the_white_space_1095671.html
18) http://science.howstuffworks.com/life/evolution/evolution11.htm
19) http://bio-complexity.org/ojs/index.php/main/article/view/BIO-C.2011.1

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How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept 1

Several theoretical and experimental studies have endeavored to derive the minimal set of genes that are necessary and sufficient to sustain a functioning cell under ideal conditions, that is, in the presence of unlimited amounts of all essential nutrients and in the absence of any adverse factors, including competition. A comparison of the first two completed bacterial genomes, those of the parasites Haemophilus influenzae and Mycoplasma genitalium, produced a version of the minimal gene set consisting of ~250 genes.

Very similar estimates were obtained by analyzing viable gene knockouts in Bacillus subtilis, M. genitalium, and Mycoplasma pneumoniae. With the accumulation and comparison of multiple complete genome sequences, it became clear that only ~80 genes of the 250 in the original minimal gene set are represented by orthologs in all life forms. For ~15% of the genes from the minimal gene set, viable knockouts were obtained in M. genitalium; unexpectedly, these included even some of the universal genes. Thus, some of the genes that were included in the first version of the minimal gene set, based on a limited genome comparison, could be, in fact, dispensable. The majority of these genes, however, are likely to encode essential functions but, in the course of evolution, are subject to nonorthologous gene displacement, that is, recruitment of unrelated or distantly related proteins for the same function. Further theoretical and experimental studies within the framework of the minimal-gene-set concept and the ultimate construction of a minimal genome are expected to advance our understanding of the basic principles of cell functioning by systematically detecting nonorthologous gene displacement and deciphering the roles of essential but functionally uncharacterized genes.



1.https://www.ncbi.nlm.nih.gov/books/NBK2227/

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Three Subsets of Sequence Complexity and Their Relevance to Biopolymeric Information - David L. Abel and Jack T. Trevors - Theoretical Biology & Medical Modelling, Vol. 2, 11 August 2005, page 8
"No man-made program comes close to the technical brillia
nce of even Mycoplasmal genetic algorithms. Mycoplasmas are the simplest known organism with the smallest known genome, to date. How was its genome and other living organisms' genomes programmed?"
http://www.biomedcentral.com/content/pdf/1742-4682-2-29.pdf

First-Ever Blueprint of 'Minimal Cell' Is More Complex Than Expected - Nov. 2009
Excerpt: A network of research groups,, approached the bacterium at three different levels. One team of scientists described M. pneumoniae's transcriptome, identifying all the RNA molecules, or transcripts, produced from its DNA, under various environmental conditions. Another defined all the metabolic reactions that occurred in it, collectively known as its metabolome, under the same conditions. A third team identified every multi-protein complex the bacterium produced, thus characterising its proteome organisation.
"At all three levels, we found M. pneumoniae was more complex than we expected,"
http://www.sciencedaily.com/rele.../2009/11/091126173027.htm

There’s No Such Thing as a ‘Simple’ Organism - November 2009
Excerpt: In short, there was a lot going on in lowly, supposedly simple M. pneumoniae, and much of it is beyond the grasp of what’s now known about cell function.
http://www.wired.com/wiredscience/2009/11/basics-of-life/

Simplest Microbes More Complex than Thought - Dec. 2009
Excerpt: PhysOrg reported that a species of Mycoplasma,, “The bacteria appeared to be assembled in a far more complex way than had been thought.” Many molecules were found to have multiple functions: for instance, some enzymes could catalyze unrelated reactions, and some proteins were involved in multiple protein complexes."
http://www.creationsafaris.com/crev200912.htm#20091229a

To Model the Simplest Microbe in the World, You Need 128 Computers - July 2012
Excerpt: Mycoplasma genitalium has one of the smallest genomes of any free-living organism in the world, clocking in at a mere 525 genes. That's a fraction of the size of even another bacterium like E. coli, which has 4,288 genes.,,,
The bioengineers, led by Stanford's Markus Covert, succeeded in modeling the bacterium, and published their work last week in the journal Cell. What's fascinating is how much horsepower they needed to partially simulate this simple organism. It took a cluster of 128 computers running for 9 to 10 hours to actually generate the data on the 25 categories of molecules that are involved in the cell's lifecycle processes.,,,
,,the depth and breadth of cellular complexity has turned out to be nearly unbelievable, and difficult to manage, even given Moore's Law. The M. genitalium model required 28 subsystems to be individually modeled and integrated, and many critics of the work have been complaining on Twitter that's only a fraction of what will eventually be required to consider the simulation realistic.,,,
http://www.theatlantic.com/.../to-model-the.../260198/

twitter discussion criticizing the cell model.. - 2012
Umm – claims of first full computer simulation of an organism seem, well, way way overhyped… one of the worst NY Times science articles I have seen in a while… I do not think they made a complete model …
Another commenter, Steffen Christensen, voiced his agreement:
Aye: a model is NOT a complete simulation…There are what, 1000s of molecule types in a typical cell, and their model tracks less than 30?!? They might’ve done a better job of it. You know, modeled spatial interactions, 1000s of moieties, etc… As it is, I just feel… disappointed.
http://phylogenomics.blogspot.jp/.../for-those-interested...

Microbe with stripped-down DNA may hint at secrets of life - Mar 24, 2016
Excerpt: The newly created bacterium has a smaller genetic code than does any natural free-living counterpart, with 531,000 DNA building blocks containing 473 genes. (Humans have more than 3 billion building blocks and more than 20,000 genes).
But even this stripped-down organism is full of mystery. Scientists say they have little to no idea what a third of its genes actually do.
"We're showing how complex life is, even in the simplest of organisms," researcher J. Craig Venter told reporters. "These findings are very humbling.",,,
The genome is not some one-and-only minimal set of genes needed for life itself. For one thing, if the researchers had pared DNA from a different bacterium they would probably have ended up with a different set of genes.,,,
The genome is "as small as we can get it and still have an organism that is ... useful," Hutchison said.,,,
http://hosted.ap.org/dynamic/stories/U/US_SCI_SKINNY_GENES

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