Paul Giem on overlapping genetic codes

_{Denyse O'Leary

December 24, 2014

Genetics, News}

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In the book “Biological Information: New Perspectives” Chapters 6 and 9 (at least) argue that stretches of DNA can have multiple functions encoded into them. We will partially evaluate the strength of the evidence behind that argument.

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#87 addendum wd400 Please, be aware that I'm a student (autodidact), hence I'm interested in learning many things I still don't know about biology. Any useful information I can gather from our discussions is very appreciated. My current scientific ignorance could make me write questions that make no sense. On top of that, to make things more difficult to me, English is not my first language. Any corrections are very welcome! Thanks. [don't worry, blogs are not the main source of information for my studying. There are free online classes provided by several universities. I've taken a few of those. They are pretty cool, because I can attend the same lecture multiple times, make the professor repeat any part of his lecture several times, learn at my slow pace, no peer pressure, and many other explicit or implicit benefits. Also books like "biochemistry for dummies" and others can be helpful to beginners like me. Also a number of specialized online journals are available. In the university library I can access most of their contents freely. Just need to enroll in a free course to get a temporary visitor card for the library. There are other available tools and ways to facilitate learning. In this blog gpuccio and other folks here have helped me to understand a few concepts I did not get quite well from other sources. As you can see, there are some benefits from being in this blog.]Dionisio_{December 29, 2014
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#86 wd400
You can just look at a coding sequence and know the corresponding peptides.
Look where? in the DNA? what coding sequence? the nucleotide sequence within the DNA? Does that nucleotide sequence in the DNA always tell you the final sequence of amino acids? Does that nucleotide sequence in the DNA always translate into a sequence of amino acids? Do portions of the DNA nucleotide sequence get involve in regulatory or controlling mechanisms? Are there any portions of the DNA nucleotide sequence that may be associated with both protein coding and regulatory/controlling mechanisms? Is the term "overlapping" being used for the case of (1) DNA nucleotide sequences that code for proteins, and also in the case of (2) DNA nucleotide sequences that get associated with regulatory/controlling mechanisms, and also in the cases (3) where DNA nucleotide segments may have dual functioning (duons), and in (4) other cases? Which of the above mentioned cases have been in textbooks since the eighties? Which ones are more recent? DNA_Jock is welcome to answer these questions too. [Note: I may need gpuccio to jump in and give us a hand with this, because I'm in "unknown to me territory". :)]Dionisio_{December 29, 2014
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Jacob and Monod won a Nobel for uncovering the prokayote system in 1965, the experiments that established the same in eukaryotes were done in the early 80s, and no doubt made into text books not long after. Control of gene expression is not really a code like the genetic code though. You wouldn't normally be able to look at genomic data and see when and where a gene will be expressed. You can just look at a coding sequence and know the corresponding peptides.wd400_{December 28, 2014
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DNA_Jock Do you know approximately when was the “regulatory code specifying transcription factor (TF) recognition sequences” first referenced in textbooks? See posts #14-21, 23 and 26 for examples.Dionisio_{December 28, 2014
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DNA_Jock Does the OP somehow (directly or indirectly) refer to the “regulatory code specifying transcription factor (TF) recognition sequences” too? See insightful post #63 by gpuccio. Optionally, posts #30 and 33, also by gpuccio, shed more light on this discussion.Dionisio_{December 28, 2014
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Correct.DNA_Jock_{December 28, 2014
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#81 DNA_Jock
Barrell and Sanger showed that the genetic code specifying amino acids overlaps in the genome of phage phiX174.
Ok, so that was not related to the “regulatory code specifying transcription factor (TF) recognition sequences”, right?Dionisio_{December 28, 2014
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Barrell and Sanger showed that the genetic code specifying amino acids overlaps in the genome of phage phiX174.DNA_Jock_{December 28, 2014
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Can someone see any relation between post #79, post #69 and posts 30, 33 and 63 by gpuccio ? Thanks.Dionisio_{December 28, 2014
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DNA_Jock @76
Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution DOI: 10.1126/science.1243490 Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. http://www.sciencemag.org/content/342/6164/1367.abstract?sid=10ce3b98-d907-4d26-be90-89ffa3a245fb
The “both” above refers to the original genetic code (1960?s) and the “binding factor” (1990?s – present) code. The overlapping reading frames were discovered (no allegedly about it) in 1976 by Bart Barrell.
Thank you for the clarification. Are the "overlapping reading frames discovered in 1976 by Bart Barrell" more related to the "genetic code specifying amino acids" or to the "regulatory code specifying transcription factor (TF) recognition sequences", or to both, or to none of the above, or to something else? Can someone explain this to me? Thanks in advance.Dionisio_{December 28, 2014
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#76 DNA_Jock
Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution DOI: 10.1126/science.1243490 Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. http://www.sciencemag.org/content/342/6164/1367.abstract?sid=10ce3b98-d907-4d26-be90-89ffa3a245fb
The “both” above refers to the original genetic code (1960?s) and the “binding factor” (1990?s – present) code. The overlapping reading frames were discovered (no allegedly about it) in 1976 by Bart Barrell.
Thank you for the clarification.Dionisio_{December 28, 2014
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To illustrate the monumental brick wall any evolutionary scenario (no matter what “fitness landscape”) must face, to actually get a proper 'beneficial mutation’ in a polyfunctional genome we would actually be encountering something akin to this illustration found on page 141 of the book ‘Genetic Entropy’ by Dr. Sanford.
S A T O R A R E P O T E N E T O P E R A R O T A S Sator Square http://en.wikipedia.org/wiki/Sator_Square
Which is translated ,
THE SOWER NAMED AREPO HOLDS THE WORKING OF THE WHEELS.
This ancient puzzle, which dates back to at least 79 AD, reads the same four different ways. Thus, if we change (mutate) any letter we may get a new meaning for a single reading read any one way, (as in Dawkins' weasel program), but we will consistently destroy the other 3 readings of the message with the new mutation (save for the center). This is what is meant when it is said a poly-functional genome is poly-constrained to any random mutations (Sanford: Genetic Entropy). Of note to DNA_Jock's claim that mutations 'have the opportunity to be mildly beneficial, or mildly deleterious' in an area of overlapping coding, I hold that, as Dr. Behe has shown, the beneficial mutations will almost always occur at the cost of breaking something, i.e. "The First Rule of Adaptive Evolution", and that the 'benefit' will only be beneficial in a anomalous environment, as with antibiotic resistant bacteria. A few notes to that effect:
“The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain - Michael Behe - December 2010 Excerpt: In its most recent issue The Quarterly Review of Biology has published a review by myself of laboratory evolution experiments of microbes going back four decades.,,, The gist of the paper is that so far the overwhelming number of adaptive (that is, helpful) mutations seen in laboratory evolution experiments are either loss or modification of function. Of course we had already known that the great majority of mutations that have a visible effect on an organism are deleterious. Now, surprisingly, it seems that even the great majority of helpful mutations degrade the genome to a greater or lesser extent.,,, I dub it “The First Rule of Adaptive Evolution”: Break or blunt any functional coded element whose loss would yield a net fitness gain. http://behe.uncommondescent.com/2010/12/the-first-rule-of-adaptive-evolution/ List Of Degraded Molecular Abilities Of Antibiotic Resistant Bacteria: http://www.trueorigin.org/bacteria01.asp Is Antibiotic Resistance evidence for evolution? - 'The Fitness Test' - video https://www.youtube.com/watch?v=rYaU4moNEBU Multiple Overlapping Genetic Codes Profoundly Reduce the Probability of Beneficial Mutation George Montañez 1, Robert J. Marks II 2, Jorge Fernandez 3 and John C. Sanford 4 - May 2013 Excerpt: It is almost universally acknowledged that beneficial mutations are rare compared to deleterious mutations [1–10].,, It appears that beneficial mutations may be too rare to actually allow the accurate measurement of how rare they are [11]. 1. Kibota T, Lynch M (1996) Estimate of the genomic mutation rate deleterious to overall fitness in E. coli . Nature 381:694–696. 2. Charlesworth B, Charlesworth D (1998) Some evolutionary consequences of deleterious mutations. Genetica 103: 3–19. 3. Elena S, et al (1998) Distribution of fitness effects caused by random insertion mutations in Escherichia coli. Genetica 102/103: 349–358. 4. Gerrish P, Lenski R N (1998) The fate of competing beneficial mutations in an asexual population. Genetica 102/103:127–144. 5. Crow J (2000) The origins, patterns, and implications of human spontaneous mutation. Nature Reviews 1:40–47. 6. Bataillon T (2000) Estimation of spontaneous genome-wide mutation rate parameters: whither beneficial mutations? Heredity 84:497–501. 7. Imhof M, Schlotterer C (2001) Fitness effects of advantageous mutations in evolving Escherichia coli populations. Proc Natl Acad Sci USA 98:1113–1117. 8. Orr H (2003) The distribution of fitness effects among beneficial mutations. Genetics 163: 1519–1526. 9. Keightley P, Lynch M (2003) Toward a realistic model of mutations affecting fitness. Evolution 57:683–685. 10. Barrett R, et al (2006) The distribution of beneficial mutation effects under strong selection. Genetics 174:2071–2079. 11. Bataillon T (2000) Estimation of spontaneous genome-wide mutation rate parameters: whither beneficial mutations? Heredity 84:497–501. http://www.worldscientific.com/doi/pdf/10.1142/9789814508728_0006
Moreover, although single mutations may seem to be beneficial in a limited environment, the constraint imposed on evolutionary processes by overlapping coding, on truly beneficial mutations ever happening, really shows its face when two coordinated mutations are required to confer an evolutionary benefit:
Response from Ralph Seelke to David Hillis Regarding Testimony on Bacterial Evolution Before Texas State Board of Education, January 21, 2009 Excerpt: He has done excellent work showing the capabilities of evolution when it can take one step at a time. I have used a different approach to show the difficulties that evolution encounters when it must take two steps at a time. So while similar, our work has important differences, and Dr. Bull’s research has not contradicted or refuted my own. http://www.discovery.org/a/9951 Testing Evolution in the Lab With Biologic Institute's Ann Gauger - podcast with link to peer-reviewed paper Excerpt: Dr. Gauger experimentally tested two-step adaptive paths that should have been within easy reach for bacterial populations. Listen in and learn what Dr. Gauger was surprised to find as she discusses the implications of these experiments for Darwinian evolution. Dr. Gauger's paper, "Reductive Evolution Can Prevent Populations from Taking Simple Adaptive Paths to High Fitness,". http://intelligentdesign.podomatic.com/entry/2010-05-10T15_24_13-07_00 Epistasis between Beneficial Mutations - July 2011 Excerpt: We found that epistatic interactions between beneficial mutations were all antagonistic—the effects of the double mutations were less than the sums of the effects of their component single mutations. We found a number of cases of decompensatory interactions, an extreme form of antagonistic epistasis in which the second mutation is actually deleterious in the presence of the first. In the vast majority of cases, recombination uniting two beneficial mutations into the same genome would not be favored by selection, as the recombinant could not outcompete its constituent single mutations. https://uncommondescent.com/epigenetics/darwins-beneficial-mutations-do-not-benefit-each-other/ Mutations : when benefits level off - June 2011 - (Lenski's e-coli after 50,000 generations) Excerpt: After having identified the first five beneficial mutations combined successively and spontaneously in the bacterial population, the scientists generated, from the ancestral bacterial strain, 32 mutant strains exhibiting all of the possible combinations of each of these five mutations. They then noted that the benefit linked to the simultaneous presence of five mutations was less than the sum of the individual benefits conferred by each mutation individually. http://www2.cnrs.fr/en/1867.htm?theme1=7
bornagain77_{December 28, 2014
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Box @26
Is there one scientist who holds that overlapping codes increase the probability of beneficial mutations?
Yes. Yes there is. "Synonymous" mutations have the opportunity to be mildly beneficial, or mildly deleterious. We discussed this with ericB on his "N.E.C.R.O." thread at TSZ. Dionisio @50

Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution DOI: 10.1126/science.1243490 Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. [link]
For those of us who may have reading comprehension problems, it might be worth to clarify that the term both seems to refer to two types of codes: One code that was allegedly discovered in 1976, and another code that is the subject of much more recent research.
No. The "both" above refers to the original genetic code (1960's) and the "binding factor" (1990's - present) code. The overlapping reading frames were discovered (no allegedly about it) in 1976 by Bart Barrell.DNA_Jock_{December 28, 2014
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#73 hrun0815
But I am sure you were able to figure out what I meant, right?
Yes, that's right. I was just trying to tease you a little, just for fun, so we relax our discussion. You see, this time we have been able to maintain a serious discussion, and I thank you for that, because we have been respectfully exchanging opinions. That's an encouraging sign, isn't it? :)Dionisio_{December 28, 2014
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#70 hrun0815
Now, you can claim that this does not mean you thought you were right… but that won’t be very convincing.
I can't think I'm right about a subject I'm not an expert on (and in most cases I'm very far from becoming one). That's why I ask others, who seem to know much more than I do, so they correct my comments on the discussed subject, if that's required. I could even accept a correction from you, but your comments should not contradict the known evidences. If I see a contradiction, then I could ask someone else, who seem to know more on the given subject, to clarify the issue. At the end of the day some of us would like to find the truth about the discussed subject, right? Do you see my point now?Dionisio_{December 28, 2014
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I also meant were instead of very. But I am sure you were able to figure out what I meant, right?hrun0815_{December 28, 2014
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hrun0815 @70
But it’s good to here that rather you very provoking and baiting. So be it.
Did you mean "to hear"? :) You may still have a few minutes left to edit your text and repost it, if you want to.Dionisio_{December 28, 2014
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#70 hrun0815
But it’s good to here that rather you very provoking and baiting. So be it.
Did you mean "to hear"? :)Dionisio_{December 28, 2014
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Dionisio, you first suggested that I am off topic, then implied I'm barking up the wrong tree, and then suggested that I initially was so convinced I was right and then quietly dropped off the conversation. Now, you can claim that this does not mean you thought you were right... but that won't be very convincing. But it's good to here that rather you very provoking and baiting. So be it.hrun0815_{December 28, 2014
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#67 Paul Giem Thank you for clarifying that point, which apparently confused or preoccupied some interlocutors here. However, apparently there are other objections to the OP in this thread. Here's one: is the central subject of your video (shown in the OP for this thread) related to an old issue that has been in textbooks since the eighties? (see post #2). Could it be that it has been discussed in scientific literature since the eighties, but did not make it into actual textbooks until later? Or could it be that it has become a hot subject just recently? Some articles referenced in a few posts in this discussion thread seem to point to more recent discussions on the given subject of different types of codes within the genome. However, that could be my wrong perception. At least E.N. Trifonov pointed to some of that stuff in 1989, but was that subject explained in textbooks back then? To me textbooks are books that school courses explicitly indicate as the referenced literature. I think that not all scientific books are textbooks*, but maybe I'm wrong on this too. Can you please clarify all this for us? Thank you in advance. (*) some textbooks seem to contain subtle propaganda for certain not-so-clear agendas.Dionisio_{December 28, 2014
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#66 hrun0815
I do want to offer you one more piece of advice: Don’t automatically conclude in Internet discussions that you are right just because a counter part stopped replying. You may ‘win’ many arguments that way, but that does not increase the chances that you actually learn something or that you are in fact right.
You misunderstood my comments, again. Did I ever say I was right? Can you point to such text written by me? If I mistakenly did it, I'm willing to correct it right away. But where is it? Didn't you notice how many times I ask gpuccio and other folks in this site, who know much more than I do about the discussed subjects, to review my comments and correct them? What I wrote was an indirect invitation (or you could call it provocation or a bait) to bring you back into this thread. Apparently it worked! You came back and added another comment. Thank you. :) BTW, I appreciate your desire to teach me internet discussion manners. I can use any help I can get in that area, because I really don't know much about it. :) Kind regards.Dionisio_{December 28, 2014
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Hi guys, Sorry for the late entry. I was busy when this posted and didn't catch up on it until today (I didn't even realize that my video had been copied; not that I mind :) ). hrun0815 asked (#2),
And News, could you actually mark in your posts which part is a direct quote and which one isn’t? I’m curious who is responsible for this sentence: “We will partially evaluate the strength of the evidence behind that argument.” It’s clearly another sign of a very sharp mind so I’d like to know who to attribute it to.
From reading the rest of hrun0815's comments, I gather that his comment may be ironic and I may be in for some abuse, but I'm actually the "very sharp mind" that wrote "We will partially evaluate the strength of the evidence behind that argument.” I do hope hrun0815 likes the video a little better than s/he likes some of the comments here. The comment that was quoted actually went with this video: https://www.youtube.com/watch?v=3WZy0n60_ZU The comment that went with the above video was:
In the book "Biological Information: New Perspectives" the chapter entitled "Multiple Overlapping Genetic Codes Profoundly Reduce the Probability of Beneficial Mutation" discusses the implications of the fact that multiple DNA codes often involve the same stretch of DNA.
Again, that comment originated with me.Paul Giem_{December 27, 2014
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It seems like some folks that sounded so ‘convinced’ early in this thread, now have realized it’s much better for them to quietly withdraw from this discussion, after their ‘off topic’ tricky comments were caught up in the air. What else is new? Same ole, same ole… :)
I would stop digging. The OP talked about "overlapping genetic codes" as did I. --> on topic The OP seems to be quoted (or typically mangled in news style) and I asked for clarification. --> on topic Your attempts to point to multiple different functions does not invalidate what I wrote in the beginning. This is so obvious that I chose to simply ignore your statements. I do want to offer you one more piece of advice: Don't automatically conclude in Internet discussions that you are right just because a counter part stopped replying. You may 'win' many arguments that way, but that does not increase the chances that you actually learn something or that you are in fact right.hrun0815_{December 27, 2014
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At this point one could say that posts 30, 33 and 63 by gpuccio basically summarize the main ideas associated with this thread. Those three posts could wrap up this discussion. We still could provide more references to research papers as examples, but conceptually the bottom line has been explained in a very compacted manner in the mentioned 3 posts, though some interlocutors might not agree. Well, it's hard to please everybody, isn't it? :)Dionisio_{December 27, 2014
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gpuccio Thank you (again!) for the clarification.Dionisio_{December 27, 2014
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Dionisio: "Is the OP video talking mainly about the genetic code specifying amino acids or a regulatory code specifying transcription factor (TF) recognition sequences, or both, or none of them, or something else?" Well, in the video Paul Giem comments (very well, IMO) a paper by George Montañez, Robert J. Marks II, Jorge Fernandez and John C. Sanford. The paper is about the mathematical modeling of beneficial mutations when nucleotides are involved in multiple codes, and does not refer to specific examples. However, there are references in the bibliography. For example, this work by Trifonov: Trifonov EN (1989) Multiple codes of nucleotide sequences. Bull of Mathematical Biology 51:417–432. The original paper is in Russian, but here is the abstract: "Apart from the classical RNA-protein translation code, the genomic DNA sequences carry many other, nontriplet codes of different nature. Those of them which are at least partly deciphered are discussed in this review in the order of their estimated occupancy in the eukaryotic genome. Each of the codes is degenerate, like the triplet code. This is the basis for their coexistence in one and the same sequence, so that the same base often (if not always) belongs to several different overlapping sequence patterns. The genomic DNA sequence is, therefore, an unusual example of natural sequence compression where, apparently, each single symbol not only is not wasted, but is also used simultaneously in many superimposed messages." So, the idea is that if some nucleotides are functional at different levels and in different codes, that implies extreme functional constraint, and extreme improbability of evolving the result by random beneficial mutations. That seems to be the main point of the paper. The recent paper you referenced in your post: "Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution" http://www.sciencemag.org/content/342/6164/1367 is another good example. I think that any multiple function at the nucleotide level is a special constraint for that position. Multicode functionality is a special kind of information compression, ad it generates extreme limitations. The codes can be of the protein coding type, or just regulatory: the concept remains the same. We can have multiple overlapping ORFs, or an ORF overlapping with non coding regulatory sequences, and so on. Look at this page, for example: http://www-sequence.stanford.edu/group/yeast_deletion_project/overlapping.htmlgpuccio_{December 27, 2014
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It seems like some folks that sounded so 'convinced' early in this thread, now have realized it's much better for them to quietly withdraw from this discussion, after their 'off topic' tricky comments were caught up in the air. What else is new? Same ole, same ole... :)Dionisio_{December 27, 2014
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And what is the evidence that demonstrates "Roulette Wheel selection" simulates natural selection?Joe_{December 27, 2014
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Mung: Why don’t you download the source code and look? Dug around and found the source code for 2.0.2. It has the same problem. The algorithm divides the working fitness by a random number, which erases nearly the entire signal from working fitness. Rewriting the algorithm using Roulette Wheel selection, eliminates the meltdown they claim is inevitable. We contacted the author about this problem in 2009, but never heard back. Anyone with knowledge of how algorithms work can see the problem for themselves.Zachriel_{December 27, 2014
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However, the original version referenced in their paper definitely didn’t represent selection properly.
LoL! How would you know? We would love to see you try and make a case to support your claim.Joe_{December 27, 2014
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