Ribosomal Quality Control

In order to demonstrate the validity of viewing cells as computers that are able to manipulate information, consider the following finding.

The Ribosome: Perfectionist Protein-maker Trashes Errors

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ScienceDaily (Jan. 9, 2009) — The enzyme machine that translates a cell's DNA code into the proteins of life is nothing if not an editorial perfectionist.

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It turns out, the Johns Hopkins researchers say, that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life. "What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress, end of story," says Rachel Green, a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics in the Johns Hopkins University School of Medicine. "There's no second chance." Previously, Green says, molecular biologists thought the ribosome tightly managed its actions only prior to the actual incorporation of the next building block by being super-selective about which chemical ingredients it allows to enter the process. Because a protein's chemical "shape" dictates its function, mistakes in translating assembly codes can be toxic to cells, resulting in the misfolding of proteins often associated with neurodegenerative conditions. Working with bacterial ribosomes, Green and her team watched them react to lab-induced chemical errors and were surprised to see that the protein-manufacturing process didn't proceed as usual, getting past the error and continuing its "walk" along the DNA's protein-encoding genetic messages. "We thought that once the mistake was made, it would have just gone on to make the next bond and the next," Green says. "But instead, we noticed that one mistake on the ribosomal assembly line begets another, and it's this compounding of errors that leads to the partially finished protein being tossed into the cellular trash," she adds.

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So what is being monitored by the ribosome? Information. Material representations (amino acid sequence vs DNA sequence) of information. But, it does not only monitor it, it manipulates it as a means to an end... fidelity.

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To their further surprise, the ribosome lets go of error-laden proteins 10,000 times faster than it would normally release error-free proteins, a rate of destruction that Green says is "shocking" and reveals just how much of a stickler the ribosome is about high-fidelity protein synthesis. "These are not subtle numbers," she says, noting that there's a clear biological cost for this ribosomal editing and jettisoning of errors, but a necessary expense. "The cell is a wasteful system in that it makes something and then says, forget it, throw it out," Green concedes. "But it's evidently worth the waste to increase fidelity. There are places in life where fidelity matters."

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The ribosome is optimized to manipulate information for fidelity.

Preaching bad design: An argument from ignorance?

Over the years many people have come with arguments that systems in nature are sub-optimal, or sub-par. These arguments were used as a means to point out that they are "dumb" designs if it was the product of mind.

An example of such an argument is given by Richard Dawkins. Take his article:
The Information Challenge

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Genomes are littered with nonfunctional pseudogenes, faulty duplicates of functional genes that do nothing, while their functional cousins (the word doesn't even need scare quotes) get on with their business in a different part of the same genome. And there's lots more DNA that doesn't even deserve the name pseudogene. It, too, is derived by duplication, but not duplication of functional genes. It consists of multiple copies of junk, "tandem repeats", and other nonsense which may be useful for forensic detectives but which doesn't seem to be used in the body itself.

Luckily science moves forward and these arguments from ignorance get left behind and the proponents of these arguments fade into history as proponents of ignorance trying to sell meaningless metaphysics.

Junk DNA is a myth.
Examples abound of research finding fascinating functions for these previously thought non-functional parts of the genome (out of ignorance and bad metaphysics-- Dawkins: "And there's lots more DNA that doesn't even deserve the name pseudogene.").

Model unravels rules that govern how genes are switched on and off

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"Since the discovery of DNA's double helical structure more than a half century ago, scientists have focused much of their attention on understanding the 2 percent of the genome that is made up of classic genes, which code for the production of proteins. However, the instructions for turning these genes on or off are generally not in the genes themselves. Rather, they are buried in the 98 percent of the genome that was once cast aside as little more than genetic "junk."

Scientists at CSHL uncover new RNA processing mechanism and a class of previously unknown small RNAs

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A very small fraction of our genetic material--about 2%-- performs the crucial task scientists once thought was the sole purpose of the genome: to serve as a blueprint for the production of proteins, the molecules that make cells work and sustain life. This 2% of human DNA is converted into intermediary molecules called RNAs, which in turn carry instructions within cells for protein manufacture. "And what of the other 98% of the genome? It has been assumed by many to be genetic junk, a massive accumulation of “code” that evolution has rendered superfluous. Now, however, scientists are discovering that the vast bulk of the DNA in our genomes, while it does not “code” for the specific RNA molecules that serve as templates for protein synthesis, do nevertheless perform various kinds of work."

'Junk' DNA May Have Important Role In Gene Regulation

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ScienceDaily (Oct. 20, 2008) — For about 15 years, scientists have known that certain "junk" DNA -- repetitive DNA segments previously thought to have no function -- could evolve into exons, which are the building blocks for protein-coding genes in higher organisms like animals and plants. Now, a University of Iowa study has found evidence that a significant number of exons created from junk DNA seem to play a role in gene regulation.

Well, it is not only supposedly "junk DNA" that was used for these kind of arguments. The vertebrate eye has been preached to be a bad design. Why? Why is it a bad design?

The human eye contain bona fide optical fibers to conduct light and here is a nice illustration. Besides the design arose 40-60 times during evolution, like evolution was biased (converged on an optimal design) towards such a structure. So why is it sub optimal? Are proponents of these arguments going to suggest a better design with all the blueprints? Thought not, arguments from ignorance are short on design.

Why was it suggested that the appendix is useless and functionless, instead of just admitting "we are still looking into it".
A few articles discussing its function:
1) Dasso JF. Howell MD. 1997. "Neonatal appendectomy impairs mucosal immunity in rabbits." Cellular Immunology. 182(1):29-37.
2) Dasso JF. Obiakor H. Bach H. Anderson AO. Mage RG. 2000. "A morphological and immunohistological study of the human and rabbit appendix for comparison with the avian bursa." Developmental & Comparative Immunology. 24:8:797-814.
3) Fisher, RE. 2000. "The primate appendix: a reassessment." The Anatomical Record (New Anatomist) 261:228-236.
4) Weinstein PD. Mage RG. Anderson AO. 1994. "The appendix functions as a mammalian bursal equivalent in the developing rabbit." Advances in Experimental Medicine & Biology. 355:249-53.
5) A more detailed survey of the evidence, with numerous references to other technical literature, showing that the appendix is not a vestigial organ can be found in J.W. Glover, The Human Vermiform Appendix—a General Surgeon’s Reflections, CEN Technical Journal, 3:31–38, 1988.

In short:
The appendix contains a high concentration of very specialized structures called lymphoid follicles (also found throughout the GIT). Lymphoid follicles in the appendix produce cells that produce antibodies that control which essential bacteria come to reside in the caecum and colon in neonatal life. The "strategic" placement of the appendix is important during the development of neonatal life in the setup of healthy intestinal flora therefore neonatal appendectomy will impair mucosal immunity.

"The appendix's job is to reboot the digestive system..." and "acts as a good safe house for bacteria,".

It might not be that important in later life and it can be removed, but so can your one kidney, your stomach, an eye, small intestines, reproductive organs etc. Are these bad designs then as well? See... these arguments have no force. Empty arguments from ignorance...



And the cilium? Until the 1990s, the prevailing view of the primary cilium was that it was merely a vestigial organelle, without important function (wiki). Seems like pretty high-tech structures to me?

Primary Cilium As Cellular 'GPS System' Crucial To Wound Repair

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ScienceDaily (Dec. 25, 2008) — The primary cilium, the solitary, antenna-like structure that studs the outer surfaces of virtually all human cells, orient cells to move in the right direction and at the speed needed to heal wounds, much like a Global Positioning System helps ships navigate to their destinations.

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What we are dealing with is a physiological analogy to the GPS system with a coupled autopilot that coordinates air traffic or tankers on open sea," says Soren T. Christensen, describing his recent research findings on the primary cilium, the GPS-like cell structure, at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17, 2008 in San Francisco. Christensen and his colleagues at the University of Copenhagen in Denmark and the Albert Einstein School of Medicine in the Bronx studied the primary cilia in lab cultures of mice fibroblasts, the cells that along with related connective tissues sculpt the bulk of the mammalian body.

So we think we have designed GPS systems?

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"The really important discovery is that the primary cilium detects signals, which tell the cells to engage their compass reading and move in the right direction to close the wound," Christensen explains.

Purposefully communicating information as a means to an end... wound healing.

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The researchers suspect this cellular GPS system plays roles other than wound healing. The primary cilia could serve as a fail-safe device against uncontrolled cell movement, says Christensen. Without chemical stimulation, the primary cilia would restrain cell migration, preventing the dangerous displacement of cells that is associated with invasive cancers and fibrosis, the scientists explain. On the other hand, defective primary cilia might fail to provide correct directional instructions during cell differentiation. This failure could be another link connecting primary cilia to severe developmental disorders, the researchers suggest. Protruding through the cell membrane, primary cilia occur on almost every non-dividing cell in the body. Once written off as a vestigial organelle discarded in the evolutionary dust, primary cilia in the last decade have risen to prominence as a vital cellular sensor at the root of a wide range of health disorders, from polycystic kidney disease to cancer to left-right anatomical abnormalities.

Demonstrating the vacuity of preaching sub-optimal design... an idea from faulty Darwinian reasoning?

And taking clues from original design (cellular machinery) to design our own optimal nanotechnology? Does that make the original design optimal/above par/good?

Clockwork That Drives Powerful Virus Nanomotor Discovered

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Because of the motor's strength--to scale, twice that of an automobile--the new findings could inspire engineers designing sophisticated nanomachines. In addition, because a number of virus types may possess a similar motor, including the virus that causes herpes, the results may also assist pharmaceutical companies developing methods to sabotage virus machinery.

Related article:
Biologists Learn Structure, Mechanism Of Powerful 'Molecular Motor' In Virus

One has to wonder were the next spate of these arguments are going to come from? Perhaps the low optimality of the genetic code? Perhaps not... Maybe the inefficiency of biomolecular machines? Maybe not...

Arguments from bad design should be taken with a pinch of salt as they are often made out of ignorance with hidden meaningless and mindless metaphysical propositions.

Computers Making Computers?

An interesting article authored by Antoine Danchin from the Pasteur Institut was recently published and is sure to bring forth much discussion.
Bacteria as computers making computers

Various efforts to integrate biological knowledge into networks of interactions have produced a lively microbial systems biology. Putting molecular biology and computer sciences in perspective, we review another trend in systems biology, in which recursivity and information replace the usual concepts of differential equations, feedback and feedforward loops and the like. Noting that the processes of gene expression separate the genome from the cell machinery, we analyse the role of the separation between machine and program in computers. However, computers do not make computers. For cells to make cells requires a specific organization of the genetic program, which we investigate using available knowledge. Microbial genomes are organized into a paleome (the name emphasizes the role of the corresponding functions from the time of the origin of life), comprising a constructor and a replicator, and a cenome (emphasizing community-relevant genes), made up of genes that permit life in a particular context. The cell duplication process supposes rejuvenation of the machine and replication of the program. The paleome also possesses genes that enable information to accumulate in a ratchet-like process down the generations. The systems biology must include the dynamics of information creation in its future developments.

The quantum teleportation experiments have demonstrated that information can be viewed as a fundamental irreducible property of physics (informationalism). Systems biology is moving in that same direction, as viewing cells as computers with machinery and software makes it possible to view information as a fundamental category of nature and all future developments of systems biology can include this concept when looking at cells.

There are many interesting passages in this article. A few of these are going to be highlighted for discussion.

Historically, systems biology follows on from molecular biology, a science based on many concepts more closely linked to arithmetic and computation than to classical physics or chemistry. Molecular biology relies heavily on concepts such as ‘control’, ‘coding’ or ‘information’, which are at the heart of arithmetic and computation. To accept the cell as a computer conjecture first requires an exploration of the concept of information, in relation to the concept of genetic program.

Cellular processes are exquisitely controlled and carried out by remarkable biomolecular machines. The software needed to coordinate these processes is located in a fairly optimal genetic code that is optimized for evolution and maintains its own functional integrity.

The Austrian mathematician Kurt Godel showed that arithmetic (the science of whole numbers) can make statements about itself. To substantiate this remarkable claim, which implies that just manipulating whole numbers with the rules of arithmetic can generate novel information, G¨odel used a simple trick. He coded the words used in Number Theory as integers (e.g. four, which is quatre in French, vier in German and tessera in Greek, can be coded by 4) and used the corresponding code to translate propositions of arithmetic. This generated a large whole number, which could be manipulated by the rules of arithmetic, and after a sequence of operations, this manipulation generated another whole number. The latter could be decoded using the initial code. Godel’s trick was to drive the sequence of operations modifying the initial statement, to lead to a very particular conclusion. When decoded, the manipulated sequence translated into a particular proposition, which, briefly, stated: ‘I am impossible to prove’. In other words, arithmetic is incomplete, i.e. some propositions of arithmetic can be understood as valid; yet they cannot be proven within the frame of arithmetic. But this ‘incompleteness’ can also be seen as a positive feature; it is what allows the creation of new information – in Godel’s case, the statement of a fact of which the world was previously unaware. In his book, Hofstadter showed that the genetic code, which enables the world of nucleic acids to be translated into the world of proteins, which in turn manipulate nucleic acids, behaves exactly as Godel’s code does. This implies that manipulating strings of symbols, via a process that uses a code, can generate novel information. Of course, in the case of nucleic acids and proteins, there is no Godel to drive the process, and no need for one: while Godel knew what he was aiming at, living systems will accumulate information through recursivity, without any design being required. We only perceive a design because the end result is familiar to us, and thus seems more ‘right’ than any other possible result. But what we commonly term the ‘genetic program’ because it unfolds through time in a consistent manner is not a programme with an aim – it is merely there, and functions because it cannot do otherwise.

Why can't the function of the program be to actively manipulate information as a means to an end... self-replication and preservation. Later in the article something similar to this is actually suggested:

The reluctance of investigators to regard information as an authentic category of Nature suggests that, at this point in the present review of the literature, it may still be difficult for the reader to accept that a cell could behave as a computer. Indeed, what would the role of computation be in the process of evolution? We have already provided some elements of the answer to the question: Turing showed that the consequence of the process of computation along the lines he outlined is that his machine would be able to perform any conceivable operation of logic or computation by reading and writing on a data/program tape. Stated otherwise, and in a way that is easier to relate to biology, the machine manipulates information and, because arithmetic is incomplete [as illustrated in the introduction above (Hofstadter, 1979)], it is able to create information. The machine is therefore in essence unpredictable (Turing, 1936–1937), but not in a random way – quite the contrary, in a very interesting way, as lack of prediction is not due to lack of determinism, but due to a creative action that results in novel information. If the image is correct, then it shows that living organisms are those material systems that are able to manipulate information so as to produce unexpected solutions that enable them to survive in an unpredictable future (Danchin, 2003, 2008a).

There we go, organisms can be viewed as entities that are able to manipulate information as a means to an end. Why would it be difficult to accept that cells to behave like computers? Yet, cells are capable of more than computers, e.g. self-replication and autonomous manipulation of information.

A form of endogenous adaptive mutagenesis (EAM) is also being alluded to in the article:
Living organisms are, therefore, infinitely far removed from the clockwork mechanicism that superficial opponents of molecular biology associate with the widespread analytical stance they call ‘reductionism’ (Lewontin, 1993). It is important to emphasize here that, in the Turing machine, the machine is not only allowed to read the program but also to write on it. If, then, the conjecture of the cell as a Turing machine is valid, apparent paradoxes such as the controversial ‘adaptive mutations’ that enable the cell to invent novel metabolic pathways should not be unexpected (Cairns et al., 1988; Danchin, 1988b).

There is also room for drawing parallels between evolution, memetic algorithms and designed molecular docking programs.

Finally, we must note that the algorithmic approach, presented when considering the genetic program as an authentic program in a Turing machine (Danchin, 2003), identifies two completely different levels: the level of the program and the level of the machine.

The article continues to discuss at length the parallels between our own created information processing systems (computers) and molecular processes fundamental to life. The article is sure to provide information for many more interesting blog discussions.