Genome complexity: codes within codes? (Introduction)

by David Turell , Thursday, April 27, 2017, 00:53 (2550 days ago) @ David Turell

A set of three letters (a codon) denotes an amino acid. Now researchers that there may be more complex relationships between groups of codons:

https://www.evolutionnews.org/2017/04/genetic-code-complexity-just-tripled/

"The so-called central dogma of molecular biology states the process for turning genetic information into proteins that cells can use. “DNA makes RNA,” the dogma says, “and RNA makes protein.” Each protein is made of a series of amino acids, and each amino acid is coded for by sets of “triplets,” which are sets of three informational DNA units, in the genetic code.

"University of Utah biologists now suggest that connecting amino acids to make proteins in ribosomes, the cell’s protein factories, may in fact be influenced by sets of three triplets – a “triplet of triplets” that provide crucial context for the ribosome.

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"Neo-Darwinian evolution is supposed to work by mutating DNA codons, either making them “synonymous” with the prior codon (i.e., yielding the same amino acid), or “non-synonymous” (i.e., putting a different amino acid in its place, potentially affecting the resulting protein). If codons could be treated as independent entities acted on by natural selection, Darwinians at least understood the challenge before them. If these researchers are correct, the stakes just skyrocketed.

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"The authors of the PNAS paper, Hughes and Chevance, describe what drove them to examine the context for each triplet codon. They were playing with the genes for a component of the bacterial flagellum named FlgM when they noticed something interesting:

"Changing the codon on one side of the defective codon resulted in a 10-fold increase in FlgM protein activity. Changing the codon on the other side resulted in a 20-fold decrease. And the two changes together produced a 35-fold increase. “We realized that these two codons, although separated by a codon, were talking to each other,” Hughes says. “The effective code might be a triplet of triplets.”

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"The “triplet of triplets” problem helps explain why you can’t easily get the same expression pattern by substituting a plant or animal protein in a bacterium, a lab procedure called heterologous expression. One doesn’t just tinker with a particular codon and expect to get the same result in a different organism that has a different expression context. The particular codon used affects downstream factors, including tRNA modifications, which the authors say are extensive in every organism.

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"The difficulty for natural selection would be in finding codon optimization for a given gene. If the speed through a codon is dependent on the 5′ and 3′ flanking codons, and the flanking codons are dependent on their 5′ and 3′ flanking codons, then selection pressure on a single codon is exerted over five successive codons, which represent 615 or 844,596,301 codon combinations. If modified tRNAs interact with bases in a codon context-dependent manner that differs among species depending on differences in tRNA modifications, ribosome sequences, and ribosomal and translation factor proteins, it is easy to understand why many genes are poorly expressed in heterologous expression systems in which codon use is the primary factor in the design of coding sequences for foreign protein expression. The potential impact of differences in tRNA modifications represents a significant challenge in designing genes for maximal expression whether by natural selection or in the laboratory.

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"Data presented here support a model in which the evolutionary selection pressure on a single codon is over five successive codons, including synonymous codons.

"The more that natural selection has to “think” about (if you’ll pardon the expression), the less able it will be to get things right. More accurately, it’s going to take a lot more of what David Berlinski calls “sheer dumb luck” to find a beneficial change. If there are 844,596,301 codon combinations to worry about, it’s like having to get many more numbers right in Powerball than you thought when you bought your lottery ticket.

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"The tRNA modifications vary throughout the three kingdoms of life and could affect codon–anticodon pairing. The differences in tRNA modifications could account for differences in synonymous codon biases and for the effects of codon context (the ability to translate specific triplet bases relative to specific neighboring codons) on translation among different species. Here, using in vivo genetic systems of Salmonella, we demonstrate that the translation of a specific codon depends on the nature of the codons flanking both the 5′ and 3′ sides of the translated codon, thus generating higher-order genetic codes for proteins that can include codon pairs and codon triplets."

Comment: It is not surprising to find more complexity. The original dogma re' DNA and RNA was much too simple to explain how the code runs life. This coding system did not arise by chance.