May 26, 2004 | David F. Coppedge

Can a Cell Improve by Lowering Its Standards?

The title of a paper in PNAS is intriguing: “Artificially ambiguous genetic code confers growth yield advantage.”  An international team claims to have created a beneficial mutation.  They removed the editing ability of a protein involved in translating the genetic code, and got it to survive in a nutrient-starved environment.  They suggest that the resulting misspellings might have provided a primitive cell with more options for evolution.
    The protein they mutated is one of the family of 20 molecular machines that hitches the correct (canonical) amino acid to its DNA template (anticodon).  One of these aminoacyl-tRNA synthetases has a hard time distinguishing between two very similar amino acids, isoleucine and valine, so an additional “editing” step corrects any “typos” that occur.  These scientists essentially removed the editor.  Then they gave the cell stronger concentrations of valine and other noncanonical amino acids, some of which are toxic.  On the one hand, the wild-type (normal) strain with the editor did better under high concentrations of toxic noncanonical amino acids.  But when starved for isoleucine, the mutated strain, without the editor getting in the way, had more options.  This apparent flexibility led the scientists to suggest that such looseness in standards could have been an advantage during the early evolution of the genetic code:

In summary, a stable and robust strain with an ambiguous code, and thus harboring statistical [e.g., non-coded] proteins, was created by irreversible ablation of the editing activity of a single tRNA synthetase.  The WT [wild-type, or normal] strain, with its full complement of editing activities, has the decided advantage of being more resistant to the potential toxicity of elevated concentrations of noncoding amino acids (for example, norvaline) (Figs. 3 and 4).  However, the editing-deficient strain with its statistical proteins has the capacity to use noncanonical amino acids to fill in at codons specifying (but starved for) particular amino acids such as isoleucine.  This capacity is advantageous in circumstances when the organism is confronted with modest concentrations of various amino acids that might have been the only available building blocks for proteins in an early environment.  The lack of both specific resources and competing species may have favored early organisms that could maximize yield and therefore maximize the chances of spreading to new resource patches that would otherwise go unused.  Thus, organisms with the capacity to generate statistical proteins could plausibly have served as intermediates in the evolution of early living systems.


1Pezo et al., “Artificially ambiguous genetic code confers growth yield advantage,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0402893101, published online before print May 26, 2004.

If lies and nonsense make you angry, you should be angry at this paper.  You should not be intimidated by the fact it was written by nine PhDs.  You should not be swayed by its presence in the journal of the prestigious National Academy of Sciences.  You should not be dazzled by the jargon.  If it’s baloney, it stinks as bad in a castle as in a shack.
    These scientists, drunk on Darwinism, are trying to make us believe that lowering your standards makes you stronger.  By analogy, firing the proofreader makes the newspaper better.  Firing the coach makes the athlete stronger.  Firing the sergeant makes the army squad better prepared for the contingencies of battle.  Baloney, baloney, baloney.
    When in a restaurant, will you maintain better health by restraining your baser appetites and restricting yourself to a well-balanced meal?  Of course.  But if you were trapped in a candy store, could you survive a little while on chocolate?  Delicious in small quantities, and better than going hungry, that doesn’t mean you should make it your daily diet.  These scientists forced normal cells to be starved for isoleucine, an essential nutrient for healthy proteins.  The normal cells did not want to eat the unhealthy ingredients that were available; they had a coach ordering them to keep off the chocolate.  But other cells, free of such discipline, engorged themselves and at least didn’t starve.  So the fatsos outqualify the hunks for the Olympics.  If you can believe that, you can believe the phony baloney premise of this paper.
    Darwinian articles often dodge personal responsibility by (1) flat-out bluffing, or (2) using passive voice verbs that cover up their own shame.  Look at this example: “The modern genetic code appeared ~3 billion years ago [Sez who?  Were you there?] …. The code itself is thought to have started in a primitive form [Who thought so?  Own up, you Darwin Party dogmatists], perhaps with codons composed of two rather than three nucleotides [where is the evidence for that?] and with different amino acids not precisely assigned to specific codons” [who made up this howler?]  It sounds pompously aloof to say “It is thought” rather than “I think this elaborate, complex system of codes and translators began from random letters in a primitive soup.”  By saying It is thought and leaving the subject undefined, the propagandist gives the reader a subliminal impression that somebody important thinks so, somebody authoritative thinks so, or that everybody who knows anything thinks so.  Don’t be fooled.
    Did these scientists find any evidence that their lowering of editing standards actually made their variants fitter?  No.  Did they demonstrate that the incorporation of noncanonical amino acids into the protein conferred any new functional advantage?  No.  Did they provide any empirical evidence that the genetic code began in a primitive state, without proofreading?  No.  Did they provide any historical evidence, or any analogies from present systems, that a complex, proofreading system can improve by lowering standards?  No.  Did they use certified lab techniques?  Yes.  Did they use their brains?  No.
    One thing they did do: they won Stupid Evolution Quote of the Week:  “Because they could opportunistically use whatever amino acids were available to complete a protein sequence, organisms harboring statistical proteins could have had a selective advantage in a primitive environment.  Also, by having many closely related versions of the same basic sequence, variants with a particular catalytic activity could be produced.  These microvariants might have special adaptive advantages, much in the way that one or more mutations in an enzyme can enhance its activity or broaden its specificity.  The selective advantages of more complex organisms that were able to produce their own amino acids and are dependent on higher specificity eventually forced replacement of the ancient statistical systems.  Remains of ambiguous codes are still observed in nature as in the Leu/Ser ambiguity in Candida sp. [prove it].”  Coulda, woulda, shoulda.  Gimme a break.  I thought I was in science class, not Fantasyland.
    As explained earlier (see 07/21/2003 and 06/29/2003 headlines), the aminoacyl-tRNA synthetase family of enzymes comprise an exquisite, complex system that relies on accuracy, and they know it.  They admit, “The genetic code is established in reactions catalyzed by aminoacyl-tRNA synthetases, in which each amino acid is covalently joined to its cognate tRNA.  The tRNA bears the complementary nucleotide triplet of the code corresponding to the attached amino acid.”  In cases where similar amino acids might incorrectly attach, “Certain synthetases, including isoleucyl-tRNA synthetase (IleRS), have a second active site that clears mischarged amino acids and thereby removes errors of aminoacylation.”  The existence of code-translation and quality-control systems are hallmarks of intelligent design.
    Furthermore, they admit that incorrectly attached amino acids can be toxic: “Valine is the obvious starting point because of its structural similarity to isoleucine.  However, the effects of valine are difficult to measure because of its general toxicity in minimal media, caused by feedback inhibition of the isoleucine biosynthetic pathway.”  In other words, not only are there systems to edit out the wrong amino acid, but there are feedback pathways to ensure the toxic substance does not proliferate in the cell.  They admitted that the noncanonical amino acids were toxic: “As expected, high concentrations of valine or norvaline ultimately became toxic in the editing-deficient strain but not in its WT counterpart.
    Only in a very specific environment, where the normal cell was starved and their carefully-engineered mutant was given preferential treatment, did they see it outcompete the champ.  And on this, they want us to believe that life, the genetic code, its translation machinery, molecular factories of tens of thousands of protein motors and enzymes “emerged” by chance into streamlined tunas, fast-focus cormorant eyes, human composers, and all the rich and varied life forms today.  Thereon hangs a tale: not a tale of science, but a fairy tale about a fictional place where one needs to believe six impossible things before breakfast – Fallacy in Blunderland.

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Categories: Dumb Ideas

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