Shapiro has published scientific articles with Richard Sternberg who advocates a similar position but who has become one of the poster boys of the Discovery Institute and one of the stars of the movie Expelled: No Intelligence Allowed. Like Sternberg, Shapiro is admired by IDiots [Non-supernatural ID?: University of Chicago microbiologist James Shapiro works with ID guys, dismisses Darwinism, offers third way].
One of the characteristics Shapiro shares with the IDiots is attacking evolution. In this post I want to review a paper he published in 2009 on "Revisiting the Central Dogma in the 21st Century" (Shapiro, 2009).
The correct version of the Central Dogma of Molecular Biology is:
... once (sequential) information has passed into protein it cannot get out again (F.H.C. Crick, 1958)In other words, the flow of information is from nucleic acid to protein and never from protein to nucleic acid.
The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. (F.H.C. Crick, 1970)
The incorrect version of the Central Dogma of Molecular Biology is what Crick referred to as the "Sequence Hypothesis" and what we now know as a simplified version of the standard pathway for information flow from genes that specify a protein product. The incorrect version is often presented in textbooks as the real Central Dogma although that's slowly changing [The Central Dogma Strawman].None of this should be a problem for someone who is writing a scholarly article for the scientific literature since we expect such a person to have read the relevant references (Crick, 1958; Crick, 1970). They should get it right. Let's see how Shapiro does when he says ...
The concept was that information basically flows from DNA to RNA to protein, which determines the cellular and organismal phenotype. While it was considered a theoretical possibility that RNA could transfer information to DNA, information transfer from proteins to DNA, RNA, of other proteins was considered outside the dogma and "would shake the whole intellectual basis of molecular biology [Crick, 1970].That sounds pretty good but the first part is a little troubling. Which version does Shapiro actually believe he's "revisiting"?
For that we have to look to a paper he published last year (Shapiro, 2010) where he says ...
Crick's central dogma of molecular biology:Oh dear, he's got the wrong version. This doesn't look good.
1. DNA --> 2x DNA
2. DNA --> RNA --> protein --> phenotype
The 2009 paper lists a whole bunch of things wrong with the central dogma but I'll just mention the ones under "Basic Molecular Functions."
The molecular analysis of fundamental biochemical processes in living cells has repeatedly produced surprises about unexpected (or even "forbidden") activities. A short (and partial) list of these activities provides may illustrative complications or contradictions of the central dogma.None of these things complicate or contradict the correct version of the Central Dogma of Molecular Biology. They don't even conflict with the general flow of information diagram that we see in the textbooks since that diagram is meant to represent a simple version of information flow from DNA to protein. The fact that some species might have a few extra adornments isn't really a problem. Biology is full of exceptions to general rules.
- Reverse transcription ....
- Posttranscriptional RNA processing ....
- Catalytic RNA ....
- Genome-wide (pervasive) transcription ....
- Posttranslational protein modification ....
- DNA proofreading and repair ....
The fact that he mentions reverse transcription is especially revealing since the reason why Francis Crick wrote his 1970 Nature paper was to dispel the notion that reverse transcription had anything to do with the Central Dogma of Molecular Biology. You only need to read the opening paragraph of that 41-year old paper to see how little things have changed.
Plus ça change (plus c'est la même chose)."The central dogma, enunciated by Crick in 1958 and the keystone of molecular biology ever since, is likely to prove a considerable over-simplification".This quotation is taken from the beginning of an unsigned article [1] headed "Central dogma reversed", recounting the very important work of Dr. Howard Temin [2] and others [3] showing that an RNA tumour virus can use viral RNA as a template for DNA synthesis. This is not the first time that the idea of the central dogma has been misunderstood, in one way or another. In this article I explain why the term was originally introduced, its true meaning, and state why I think that, properly understood, it is still an idea of fundamental importance.
So, why do people like Shapiro makes such a big deal of this? It's because claims that the Central Dogma of Molecular Biology have been overthrown1 attract attention and fit into a larger agenda. If your goal is to start a revolution in biology then the first thing you have to do is knock down the existing "dogma." It doesn't seem to matter that you are attacking a strawman. But it's a sign that the rest of your agenda isn't very sound.
1. Such claims are occurring with increasing frequency in the past ten years. It now seems that the central dogma is being falsified about three or four times a year.
Crick, F.H.C. (1958) On protein synthesis. Symp
Crick, F. (1970) Central Dogma of Molecular Biology. Nature 227:561-563. [PDF file]
Shapiro, James A. (2009) Revisiting the Central Dogma in the 21st Century. Ann. N.y. Acd. Sci. 1178:6-28. [doi: 10.1111/j.1749-6632.2009.04990.x]
Shapiro, J.A. (2010) Mobile DNA and evolution in the 21st century. Mob DNA. 1:1-14. [doi: 10.1186/1759-8753-1-4]
544 comments :
«Oldest ‹Older 401 – 544 of 544Anonymous said...on Monday, September 05, 2011 10:53:00 AM, referencing to 'the other Jim''s post of Monday, September 05, 2011 9:16:00 AM
Notice the sly partial quote from the other Jim. Leaving out the significant part:
When you open the door how are you going to determine how far it goes?
Do you not get it?
1 Anonymous does not answer the relevant question of 'the other Jim', Have any of these happened?, but goes on to malign 'the other Jim'. Not anwering 'the other Jim''s question implies nothing like actual personal threats have happened.
2 Anonymous is casting around insinuations like "sly". This casting around on insinuations is standard behaviour by Anonymous. One other reason to be fed up with Anonymous, next to the ignorance about science.
3 Anonymous never accepts responsability for his own writings.
@Allan Miller would need to track evolutionary changes in the RNA -> protein system in order to preserve the mapping in both direction
How much has the transcription and translation system changed since say the origin of eukaryotic cells ?
This is indeed highly conserved throughout Life Since LUCA. However, there are changes of detail - our mitochondria (derived from a-proteobacteria) have a couple of differences from the code used in our nuclei (derived from Archaea). The inference is that there was some divergence between LUCA and these two groups before they merged to form the eukaryotic cell.
Similar relatively minor differences abound between different groups, often hitting the same few codons. http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi has a summary of the main departures. Because of stochastic variation, some codons may be represented at somewhat more or less than 1/20th of critical coding positions. Where substantially less, this may relax selection and allow a non-catastrophic switchover in the tRNA amino acid-codon mapping. Yes, it is very highly conserved since LUCA, but may conceivably have been a tad more labile before.
In fact, I think there is good evidence that the triplet code was formerly a doublet code with triplet docking in the aaRS (1st or 3rd position immaterial) and the ribosome (all 3 positions essential). Then, for most but not all doublets, the unused position assumed greater significance - either to purine/pyrimidine or down to specific base level. This would explain redundancy - the redundancy we see is the remnant of 3rd-base redundancy in the doublet code, not an evolved optimisation protecting against certain point mutations as some (eg Hurst) say. I think it would be very difficult to evolve a suitable redundancy in a randomised triplet code, precisely because of the strong conservation one would expect.
heleen pretends to not get it. Does anyone get the obvious point?
Once you have allowed personal information to be disclosed, any person (mentally ill or not) can take that personal info and threaten the person and their family in any intimidating and dangerous way.
Moran, is 100% responsible for allowing personal information to be posted on his blog.
And to have done nothing about it even when it was explicitly brought to his attention. He is culpable.
Anonymous said... on Monday, September 05, 2011 1:40:00 PM
heleen pretends to not get it. Does anyone get the obvious point?
There is no obvious point.
Anonymous still does not answer the relevant question by 'The other Jim’: Have any of these happened?
Given that Anonymous does not answer the only relevant question: Have any of these happened?, the only possible conclusion is that nothing of this has happened. Anonymous simply is exulting in whining. For Anonymous, anything to get attention is OK.
some codons may be represented at somewhat more or less than 1/20th of critical coding positions.
Duh - I meant 1/64th.
And the point about substitutions starting from a doublet code being more feasible than shuffling an already-triplet code is that two low-usage codons are needed in the latter case. Then the more 'optimal' code has to defeat the alternative purely on the basis of point mutation resilience which, since selection must be relaxed on those codons to allow substitution in the first place, seems unlikely.
See here for an alternative view
http://www.ncbi.nlm.nih.gov/pubmed/9732450 - can't find free source I'm afraid. This - "The Genetic Code is 1 in a Million" - has been widely reported.
But here http://ukpmc.ac.uk/articles/PMC1297647/reload=0;jsessionid=3D3B08CF756CAB167B69FD952F574094 the error-tolerance idea is tested without confirmation. "[Codon coding and usage patterns] raise the question: why do all known organisms use highly error-minimizing genetic codes, but fail to minimize the errors in the mRNA messages they encode?"
I think it's because codon error-tolerance is a byproduct of the way the code evolved.
Sorry, is this a derail? :0)
heleen is good for a laugh.
He/she wants an answer and also posts:
"Actually, I would not take the word of Anonymous if he said 'yes' to the question."
I guess he/she thinks that he/she can say any absurd thing and we won't notice.
"Sorry, is this a derail?"
Compared to most of the previous comments, it's bang on topic. (And even if off-topic, it's interesting off-topic!)
http://www.ncbi.nlm.nih.gov/pubmed/9732450
"Statistical and biochemical studies of the genetic code have found evidence of nonrandom patterns in the distribution of codon assignments."
So more non-random stuff. Time for another convoluted story.
Next we will hear the refrain that we would have predicted that and "move along, nothing to see here."
http://www.ncbi.nlm.nih.gov/pubmed/9732450
"In addition, if we employ weightings to allow for biases in translation, then only 1 in every million random alternative codes generated is more efficient than the natural code."
If it's design, why not use one of those codes? You are right that it is an observation in need of an explanation but I don't think that the best explanation is design.
(As you well know, because you got this link from his post, Allan Miller also posted an alternative hypothesis for the evolution of the code.)
"Sorry, is this a derail?"
Not as far as I'm concerned.
Busy wading through the terminology, found an interactive animation (http://www.wiley.com/college/boyer/0470003790/animations/translation/translation.htm) that is clarifying some of the terms you used.
@Alan Miller
You wrote:
"This is indeed highly conserved throughout Life Since LUCA. However, there are changes of detail - our mitochondria (derived from a-proteobacteria) have a couple of differences from the code used in our nuclei (derived from Archaea). The inference is that there was some divergence between LUCA and these two groups before they merged to form the eukaryotic cell.
Similar relatively minor differences abound between different groups, often hitting the same few codons. http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi has a summary of the main departures."
I went to the link and looked around, then tried to learn a tad more about translation.
My question is, how can the same codon be translated into a different amino acid by different organisms? Is it that their tRNA functions differently?
Sorry, that should be Allan Miller.
Amazing. Even when we are on your side (harassment is bad) you find a way to misinterpret what we say. So apparently, you are sticking to anonymous posting due to some paranoia of people harassing you. This has not happened, but you are afraid that your behavoir would piss someone off to the extent they would stalk you in real life. I think this is a bit out there, but feel free to live in fear of that nutty 0.000001% of the population.
A counter example of your fears. I have a psuedonym ID. I have chosen this option due to some stupid interpretation of "intellectual property" at my current job, which means comments I make on a science-based forum would technically have to be approved by my research-director. Easier to not attach my real name.
But because I have a stable ID (even though it does not list my name or e-mail address), this means people can tell what I post, and no one can imitate me. People can then decide whether to engage in a discussion with me, and not have to guess which anonymous poster I am.
No one has tracked down my e-mail (even though I was the subject of a few Mabus attacks on another comment board.) And he was the type willing to find you and actually harass you.
This is all we are asking for. Make a psuedonym ID and keep your real identity anonymous. We can then tell which "Anonymous" you are. I suggest you use the name "I heart Shapiro".
Allan Miller said,
This is indeed highly conserved throughout Life Since LUCA. However, there are changes of detail - our mitochondria (derived from a-proteobacteria) have a couple of differences from the code used in our nuclei (derived from Archaea). The inference is that there was some divergence between LUCA and these two groups before they merged to form the eukaryotic cell.
I completely support the general basis of the post, but want to correct one point. My profile picture should tell you why ;-)
It looks like the mitochondrial code variations came after the a-proteobacteria endosymbiosis. Plant mitochondria, for instance, use the universal code.
One suggestion is that all of the mitochondrial genetic code changes are based on mito-genome streamlining. Many mitochondria, and especially in animals and yeast, encode the minimal set of tRNAs (ex. 1 proline tRNA that decodes all four CCN codons). Sort of a "super wobble" scenario for translation.
If you take the standard genetic code, you require minimum 2 isoluecines (ATA and the ATY) And two for the AGR arginine and AGY serine codon set. 2 extra tRNA genes.
If there is a bias to a smaller genome, then for instance the vertebrate mitochondrial genetic code you eliminate 2 tRNAs (the ATA-ile and the AGR-arg) with the genetic code alterations, and now encode 22 tRNA genes instead of 24. The TGA-stop to Trp change also allows the loss of an additional release factor for the TGA stop codon.
I don't even understand why Doug Dobney would even want to toil in anonytimity when he is doing such groundbreaking work on organism development, especially in the new field of pterosaur to bird development. He is truly one of the great minds of the 21st century.
Doug Dobney will eventually be viewed in the same light as Darwin by the time the history of organism development is written.
And of course, to quote the great Mr. Dobney, this is certainly not worth arguing about! (both his wonderful wife Angela and myself get a great chuckle out of this whenever he says it, which is quite often!)
"It looks like the mitochondrial code variations came after the a-proteobacteria endosymbiosis."
Yes. My understanding is that deviations from the "Universal Genetic Code" are later variants, not early divergence. When you look at the organisms and codons involved, I believe they are always in situations of high nucleotide bias and/or low gene number, such that the number of occurrences of the altered codons is very small. This fits with the idea that the code is generally fixed because changes affect so many sites simultaneously but if (and only if) this constraint disappears for a codon or two, they are then free to take on new roles.
The other Jim posted:
"No one has tracked down my e-mail (even though I was the subject of a few Mabus attacks on another comment board.) And he was the type willing to find you and actually harass you."
So you are familiar with disturbed people who are "willing to find you and harass you". Imagine if Moran allowed your personal info to be disclosed and people started threatening you and your family.
How would you feel if Moran allowed your wife's name to be posted here so that people could send threats to her by name. Or go even further and track her down.
How do others feel?
How do you feel Dr. Moran?
Anonymous said...
How do others feel?
I feel that Anonymous should stop blogging and get some mental help.
@The Other Jim
I completely support the general basis of the post, but want to correct one point.
[...]
It looks like the mitochondrial code variations came after the a-proteobacteria endosymbiosis. Plant mitochondria, for instance, use the universal code.
Yes, I stand corrected. I did blush slightly when looking at the 'departures' I'd linked and noticed that archaea, bacteria and plant plastids share commonality, rendering my pre-eukaryogenesis assertion a bit of a clunker.
And of course, mitochondria having such a tiny genome, courtesy of nurturing by the wider cell, increases the likelihood that codon substitution may be achieved without disastrous consequences - the fewer codons there are, the less likely that every single codon assignment must be conserved.
Josef Gladstone @ Tuesday, September 06, 2011 2:15:00 AM
Josef, you have done the impossible and made me agree with Anonymous. This is crossing the line. Please delete this entry with the names.
Perhaps now that you acknowledge the problem, you might go back and suggest earlier posts also be repudiated.
And mention the problem to Moran.
It is his blog. He is the one responsible for this entire dangerous situation.
@Fred
My question is, how can the same codon be translated into a different amino acid by different organisms? Is it that their tRNA functions differently?
It's down to the set of amino-acyl tRNA synthetases. A tRNA is simply a vehicle with a distinctive label, one of 64 triplet possibilities, and an amino acid on the other end. aaRS's charge one or more tRNA's with a particular acid, and it is these, not tRNA, that hold the cipher.
There are a number of possible paths for substitution related to codon usage, or lower specificity of aaRSs when the lexicon of acids was smaller. Redundancy creates opportunities for splitting a codon group between two related acids - redundancy in fact goes DOWN as the number of acids increases, but related acids remain close by in 'solution space'. But the code did become crystallised well before LUCA (hence my dubiousness about the selective optimisation explanation for redundancy - once you have a code, you can't just shuffle it about, you can only refine its divisions).
Perhaps more likely among descendants of LUCA is a temporary loss of a tRNA, creating a STOP for that codon. Its former aaRS no longer needs to recognise it. Another aaRS is then free to evolve to bind that codon. Most post-LUCA substitutions seem to have taken place around STOPs. Don't know if this will line up but the asterisks are STOPs in this selection of code variants (showing only the translation):
FFLLSSSSYY**CC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWLLLLPPPPHHQQRRRRIIMMTTTTNNKKSS**VVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWTTTTPPPPHHQQRRRRIIMMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWLLLLPPPPHHQQRRRRIIMMTTTTNNKKSSSSVVVVAAAADDEEGGGG
FFLLSSSSYYQQCC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWLLLLPPPPHHQQRRRRIIIMTTTTNNNKSSSSVVVVAAAADDEEGGGG
FFLLSSSSYY**CCCWLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CC*WLLLSPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWLLLLPPPPHHQQRRRRIIMMTTTTNNKKSSGGVVVVAAAADDEEGGGG
FFLLSSSSYYY*CCWWLLLLPPPPHHQQRRRRIIIMTTTTNNNKSSSSVVVVAAAADDEEGGGG
FFLLSSSSYY*QCC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY*LCC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FFLLSSSSYY**CCWWLLLLPPPPHHQQRRRRIIMMTTTTNNNKSSSSVVVVAAAADDEEGGGG
FFLLSS*SYY*LCC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
FF*LSSSSYY**CC*WLLLLPPPPHHQQRRRRIIIMTTTTNNKKSSRRVVVVAAAADDEEGGGG
Perhaps Josef Gladstone is a name Anonymous takes, just to carry his point. Who else would care?
nop said...
Perhaps Josef Gladstone is a name Anonymous takes, just to carry his point. Who else would care?
Easy enough to trace by IP...
http://www.ncbi.nlm.nih.gov/pubmed/9732450
"Statistical and biochemical studies of the genetic code have found evidence of nonrandom patterns in the distribution of codon assignments."
So more non-random stuff. Time for another convoluted story.
Next we will hear the refrain that we would have predicted that and "move along, nothing to see here."
Oh, blow it out your ear! No-one predicted the code, or that there would be patterns within it. But there it is, a phenomenon to be explained, and evolutionists are hardly going to duck the challenge. You would advance the hypothesis that "It's the Intelligence of Nature, move along, nothing to see here."
It is not at all clear why Nature would choose to arbitrarily switch Start and Stop codons so freely with amino acid assignments within the various codes in different genomes. Nor why an error-tolerant code would be necessary - unless the designer is infallibly aware of his own fallibility - knowing that his error correction is a bit shit, it was worth taking the precaution of clustering codons and acids with similar properties for damage limitation after his useless error correction system has muffed things up.
Always worth having a few extra tRNAs as well - the nematode C. elegans has 620, even though there are only 64 possible anticodons. There will be a damn good ID reason for that ... I expect.
Perhaps this is more to your taste:
http://www.whatabeginning.com/Misc/Genetics/Genetics_VS.htm
People have the unrealistic idea that Nature operating n the physical world can ensure any effect it intends. That is not how the world works.
Take error detection and correction in the cell. In a physical world things can always go wrong.
It is good design to accept that fact and design around that fact.
"People have the unrealistic idea that Nature operating n the physical world can ensure any effect it intends."
Is "Nature" another word for god? (Perhaps a deist god rather than theist one?) Your post implies that Nature operates outside "the physical world". This is not my understanding of nature, which *is* the physical world.
Oh, blow it out your ear! ... http://www.whatabeginning.com/Misc/Genetics/Genetics_VS.htm
Not to be outdone in the lunacy department, our very own Bozorgmehr (Atheistoclast) has published a paper on the Genetic code and the Latin language (we are not making this stuff up).
http://www.wepapers.com/Papers/122040/The_Genetic_code_and_the_Latin_language
Joseph Esfandiar Hannon Bozorgmehr
The Genetic code and the Latin language
The genetic code and the biological information it makes possible are a profound engima for scientists studying the origin of life. However, a link to natural human language, in this case Latin, is found when the frequency distribution of characters is analyzed.
And mention the problem to Moran.
It is his blog. He is the one responsible for this entire dangerous situation.
You mean the the guy that posted September 1st that he is out of the country? Perhaps you can see why that would be a bit of a useless exercise at the moment...
He tells you how to get his email at the top left of the main page. Go ahead and launch your complaint by sending an e-mail to him.
But blaiming someone for not following up on a blog post burried in the scores of posts that happened while he was away is much easier, isn't it.
@Allan Miller his error correction is a bit shit
My understanding is that if there were perfect, error free replication and translation of genetic information then there would be no variability and hence no opportunity to adapt to changes in the environment via differential reproduction.
In information theory Shannon showed that there is a coding/decoding scheme that can reduce your error rate to an arbitrarily small value but the error rate can never equal zero for a channel of a given bandwidth no matter how much power you are willing to pump into it.
Presumably the code used for the genetic "channel" has been determined by selection. The cost for a less error prone genetic replication and protein synthesis system outweighed that of a more error prone but cheaper one.
In fact higher fidelity replication may be selected against due to the decrease in variability.
In fact higher fidelity replication may be selected against due to the decrease in variability.
I'm not sure what you mean by this. My first read is that you are saying the errors are a form of diversity, which is useful. Not sure about this argument. Why do cells maintain so many mechanisms to detect and destroy their "diversity"?
But if you are refering to tranlation speed/fidelity trade-off arguments, I agree. The numbers from back in my undergrad days seemed to add up...
http://www.ncbi.nlm.nih.gov/books/NBK22421/
see 29.1.1 The Synthesis of Long Proteins Requires a Low Error Frequency
@The other Jim I'm not sure what you mean by this. My first read is that you are saying the errors are a form of diversity, which is useful. Not sure about this argument. Why do cells maintain so many mechanisms to detect and destroy their "diversity"?
If replication was perfect then there would be no variability and nothing for selection or drift to act on. As the replication process becomes more error prone the incidence of mutations increases.
In my awkward and convoluted way I'm trying to say that there must be a threshold in the ability of a cell to correct for errors that will be selected against as any increase error correction will result in a decrease in variability. And a similar result for decreases in error correction, there must be a threshold where increased variability is offset by lower fidelity copying.
I'm looking at genetics through a glass darkened by a computer science background.
Nothing too profound here, just some general observations.
I think this is the "clade selection" type idea, isn't it. It's not that variability is good for the individual in the short term, just that the only lineages to survive in the long term are those that happened to have variability.
The problem with clade selection is that I don't think it really works unless the trait in question is selectively neutral - short-term selection will always win, won't it?
The fidelity/repair trade-off is one of time and energy, I think. That's why bacterial polymerases are more error-prone than eukaryotic ones - replication time is a major force of selection on bacteria and high fidelity comes at a speed/energy cost.
There are always exceptions to the rule, Deinococcus radiodurans is a polyextremophile that is extremely resistant to radiation, it can handle about 5 order of magnitude more radiation exposure than humans.
I've seen a video where Deinococcus radiodurans is exposed to ionizing radiation and the glass container turns black but the bacteria survives.
Was it's enhanced DNA repair process developed due to a selection process or was this a neutral trait ?
There must be a significant cost associated with this repair facility so selection seems more plausible than drift.
@Steve. I agree. DNA repair is most certainly under selection. There is a trade-off between fidelity and other things and where you end up (in my opinion) is the result of this trade-off, rather than some kind of clade selection evolvability deal.
I understand now. You are talking errors in general. My comment was specifically about translation.
In that light, it makes more sense (mutatar bacterial populations can adapt faster than non-mutator populations in environmental changes, etc.)
I think that the same applies for translation, although here it is not mutation, just error. We know that some organisms - most microbes - have biased codon usage, which can either stem from mutational bias or, it seems, selection for translational speed or accuracy here. (There are not 61 different tRNAs for the 61 amino acid coding codons, some codons share a tRNA.) Allow too many errors and you will never be able to correctly translate a long protein. Be too thorough in your proof-reading during translation and you will be quickly out-competed by another individual who makes everything faster but with a few errors. (Chaperones etc. can soak these up.)
Mutator strains are a bit different. In these situations, the population has got "stuck" in a stressful environment and must "adapt or die". If a "Mutator Strain" arises, it is not because it is selected for the ability to generate new mutations faster in the future. it is selected because it has "found" the mutation needed to get out of the stress. Once adapted to the environment - or the conditions change back - mutators generally revert over time because they are less fit with their higher mutation rate.
@Steve. I agree. DNA repair is most certainly under selection. There is a trade-off between fidelity and other things and where you end up (in my opinion) is the result of this trade-off, rather than some kind of clade selection evolvability deal.
Yes - when people talk about 'optimum mutation rate', and decide it must be zero since that's where things seem to be directed, it is necessary to tease out what level it's optimal for.
At a genic-selection level, most genes can't do anything about it; we are looking at the survivorship of those few that can, the proof-readers and cross-referencers and so on. They survive by becoming attached to fitter genomes, but as efficiency becomes better and better, the benefits of improvement become less and less. So even without pleiotropic effects, selection coefficients for improvers may be high when mutation rate is high, but effectively neutral when low, meaning that drift will always buffet them away from their assumed 'goal'. And of course improvement in copy perfection in biological systems is self-limiting because directional progress demands mutations, which, as correction gets better and better, become fewer and fewer. Which is a damn good thing for evolution.
Of course, there can be mutators as well, that survive by being attached to fitter genomes in certain selective environments, leading to a potential tussle over the position of any mutation-rate 'knob'.
You people can try to change the subject to "DNA repair" but it is only a desperate attempt at diversion. You are all being very sly.
The truth is you are unable to present evidence against the actions of the intelligence of Nature, manifested through facilitated variation.
But it is not worth arguing about.
You people can try to change the subject [...]
Splutter!
You are all being very sly.
The truth is you are unable to present evidence against the actions of the intelligence of Nature, manifested through facilitated variation.
But it is not worth arguing about.
OK then. Coffee, anyone?
Once again the disturbed individual has posted a comment that mimics the style I use.
And extends it to parts of the discussion that I am not even involved in.
Once again the disturbed individual has posted a comment that mimics the style I use.
Well, Spartacus (or am I now responding to the spoof?). Hmmm, if only there were some remedy for this mimicry ... some means of labelling posts that can only emanate from your fair hand?
No, before you ask, it wasn't me.
Do people really think that if I labelled my posts in some way that a disturbed individual(s) would not simply mimic that as well. (It is foolish to post anything in this venue that provides any identity.)
Sometimes I think that your biases are such that it interferes with your ability to think.
But we all know it is just pretending on the part of the folks here.
Anonymous said... on
Thursday, September 08, 2011 1:30:00 AM
Thursday, September 08, 2011 8:07:00 AM
Thursday, September 08, 2011 8:34:00 AM
Anonymous said lots of things. All seem to be by the same person, no spoofing detectable.
Anonymous, get yourself a Google email. That is very easy. Then you can get yourself a Google profile, and that is unique. A Google profile does not tell anything about the person either, if not wanted. See every comment that starts with the orange B.
At least, if you insist on hanging round here. Why do you hang round here, given that you only pile abuse on people? You don’t know how to argue. You don’t know anything about biology. You are unable to adduce evidence to your own ideas.
heleen writes:
Why do you hang round here
Because people keep responding to him? Because when folks try to have actual scientific interchange, and Anonymous desperately tries to get the conversation back to being about him (You people can try to change the subject.... The truth is you are unable to present evidence against the actions of the intelligence of Nature...), people fall for it?
Anonymous seems to me sufficiently desperate for any sort of interchange that I would guess he is fully capable of using a sock puppet for that purpose. (Whether he's responsible for the spoof Anonymous here, I don't know and don't care.)
On Anonymous' blog, there is a very odd sort of conversation between the 'host' (Anonymous under a pseudonym) and someone posting as 'Anonymous.' (Yes, really.) I say 'odd' because both interlocutors are so similar in tone and language that it appears to me as if Anonymous may have been having a very extended conversation with himself. He may be so desperate for online conversation that he will talk to himself on his own blog.
So heleen, you can choose to ignore or engage with Anonymous. If the former, you can free up time for yourself to participate in actual scientific interchange. If the latter, you will save him the trouble of inventing people on whom to bestow his wonderful eternally unchanging theories. Up to you.
Is there agreement here that if someone wishes to keep their personal information private, then others should not disclose it?
Is there agreement on this basic point?
Larry Moran's mathematical (in)aptitude has not been overly impressive for failure to produce properly rounded percentage numbers. Now, with the demonstration of his lack of skills to subtract from the "Posted by Larry Moran at 11:45 AM 452 Comments " a click away from the "Revisiting the Central Dogma in the 21st Century 446 Comments ", it is blatant that Dr. Moran does not understand the meaning of number 6 the integer measuring the number of comments made to disappear, call it censorship, moderation, or whatever way he would like to fudge it. His (self-confessed) inaptitude in abstract sciences is unfortunate, since informatics, especially the emerging field of genome informatics, shall remain simply beyond reach for mathematical illiterates like Old Schooler Moran. Thus, he sticks to what he knows best; Badmouthing, inflicting personal damages, now not only to a pioneer of genome informatics, but also letting reveal personal data of people in his blog, with his “Anonymous” policy permitting accusations that well-known scientists parade under anonymity, etc. Those spilled by his cyber-sewage might possibly join in a class action lawsuit for the cyber-libel he elected perpetrating past the time he was properly put on legal notice. He has absolutely zero to show as an argument in the 452 (or 446?) - entries, that entirely snowed-in the cardinal issue of the demolishing of the long-gone good old Crick’s (may his soul rest in peace!) ridiculous stone-age and dead as a doornail "Central Dogma of the Molecular Biology". Mathematics aside, even artists exempt from sophistication in tensor- or fractal geometry, great sculptors reveal beautiful information from a raw slab of marble by chiseling away the excess. Though assumably a typical American visitor to European Museums, backward provincial detractor Moran just does not even get that nuance. What else is to remain? Yes, his grand-daughter is cute! He says his own daughter declared her father Moran (at min. 4:52) “stupid”. Hopefully, while he made it obvious to the World both by his blog and his confession in his YouTube, it shall remain a family secret shielded from the innocent toddler.
Do people really think that if I labelled my posts in some way that a disturbed individual(s) would not simply mimic that as well.
You just don't get it! YES!!! I label my posts as "Allan Miller", by digning on through Google Accounts. I think that guarantees that all posts from "Allan Miller" (who the hell is he anyway?) are from the same person. People could try and mimic my style, but they can't LABEL them as mine. If you got an anonymous ID - "Anonymous1" would do - no-one else could use it, and you could stop moaning about spoofing.
It seems like half of this bloody thread has been about your internet activity.
Sometimes I think that your biases are such that it interferes with your ability to think, as someone said recently.
Is there agreement here that if someone wishes to keep their personal information private, then others should not disclose it?
Is there agreement on this basic point?
Speaking just for myself: yes, I think people's right to privacy should be respected.
Allan Miller has said that he thinks
"people's right to privacy should be respected".
Anyone else think that way?
Anonymous said...
Allan Miller has said ..
that Anonymous should get itself a Google Account.
As usual, Anonymous won't listen.
Even crazier, Doug Dobney aka Socrates aka Anonymous already has multiple blogger accounts!
I used to think, because of the commitment of time to the pterosaur blog, that Doug Dobney was the real deal.
But now from reading him here, and now because of the pterosaur blog and his infuriating posting style, I'm beginning to think he really is just an elaborate troll.
Which I find pretty odd for an owner of a B&B in Peterborough to do.
From the content is seems a viable hypothesis that the owner of http://pterosaurnet.blogspot.com/, the Socrates of talkrational and our dearly beloved Anonymous are the same person. What his actual name away from the internet is is nobody’s concern. What is clear however is that this person has nothing of interest to contribute to a serious scientific discussion.
Allan Miller has said that he thinks
"people's right to privacy should be respected".
Nevertheless, it's out there now, and you can't push the worm back in its hole.
http://en.wikipedia.org/wiki/Streisand_effect
Moving on ...
"What his actual name away from the internet is is nobody’s concern. '.
So you are agreeing with Allan Miller that "people's right to privacy should be respected". Is that right?
I wonder how Allan Miller would feel if his family members were disclosed on this thread. Would he say - Oh well, it happened.
Moving on...
He wouldn't concern himself about how his wife might feel about this? And whether she was concerned that someone would seek her out.
Moving on...
Or whether his children and grandchildren could find themselves in the same dangerous situation.
Oh well.
Moving on ..
Would that be his response?
Tell me Allan Miller. Would that be your response?
Oh well.
Moving on ...?
@Anon,
Grief, why are you grumbling at me now? I haven't revealed anything about you, and I agreed that your privacy should be respected. I can't help that it hasn't been.
All "Moving on" was intended to convey is that there is nothing to be done about it now, so let's get back to biology.
Allan Miller said:
"...so let's get back to biology".
My conclusion is that with comments even approaching 500 nobody could deny that proteins altering the readability of genome sequence reveals, as it is stated by The Principle of Recursive Genome Function", the genome-epigenome (hologenome) system recursive. This is to open up the new age of recursive algorithms, such as fractal iterative recursion, where fractal defects in the regulatory sequences cause misregulation, e.g. cancer as shown in my oft-cited papers and YouTube. The recursive algorithmic approach is crystal clear in its difference from half-a-century-old obsolete "arrow models" - and gives a new direction e.g. for R&D, IT-driven postmodern pharma, diagnosis, therapy up to a cure of cancer and other "junk DNA diseases".
Allan Miller said:
"...so let's get back to biology".
My conclusion is that with comments even approaching 500 nobody could deny that proteins altering the readability of genome sequence reveals, as it is stated by The Principle of Recursive Genome Function", the genome-epigenome (hologenome) system recursive.
Damn! I thought I was going to get the last word!
Methylation (if that's what you're talking about) appears to me to be functionally equivalent to the binding of a transcription inhibitor or regulation by histone. The fact that the genome is a target for proteins does not appear either novel, or a violation of the dogma. No sequence information is passed from protein to nucleic acid, even though specific sequences are identified and (reversibly) masked - often in promoters, not even protein-coding regions.
Allan, we are still too close after the total collapse of the Dogma to be any individual's "last word". The history of science will reach a final judgement on the old sloppy statement that "No sequence information is passed from protein to nucleic acid" - once "sequence information" is defined by theories like The Principle of Recursive Genome Function and competing mathematical approaches.
Crick (or any of this blog's past or present participants ...) never defined "genome information" - just borrowed from Shannon's probabilistic definition in informatics (to measure the DNA as a two-bit stream of A,C,T,G-s).
Lack of a modern definition of "genome information" is not doing justice to the sophistication of genomic/epigenomic (hologenomic) systems - and is a challenge to professionals of biophysics.
For laypeople, it the metaphor may be useful to think of methylation and chromatin modulation modulation as the sculptor revealing dynamic "genome information" (thus genome regulation) by making sequences inaccessible - just as the sculptor masks the excess (of the marble slab) invisible. For the mathematically not overly sophisticated audience of blogs another metaphor is to realize that a defective DVD may contain all "information" of a movie - but any segment can be truncated (changing the Shannon-bit information of any length of the remaining movie totally zero) if the readability is rendered impossible.
At Crick's time of conceiving his Dogma (1956) "sequence information" was simply just not defined - with methylation itself barely discovered.
Of course, strong suspicion and modern evidence that methylation and chromatin modulation play crucial roles in genome regulation (and thus, in cancer) is of course not "news" - however, an algorithmic understanding how fractal defects lead to aberrant methylation and chromatin modulation to derail fractal recursive genome function is not only in the leading edge of The Principle of Recursive Genome Function, but given that recursive algorithms are software-enabling, they make defense-based high-performance-computing the new smart weaponry of the "new war on cancer".
The issue is not ideology, nor is entertainment - but a life or death challenge, making obsolete dogmas simply not permitted to stand in the way.
@Allan Miller. In honeybees and some (many?) other insects, I think that methylation is actually prevalent in the coding sequence.
But, it is true, methylation does not violate the Central Dogma as proposed by Crick, and the naive interpretation based on the Watsonified version was violated so long ago that it's just silly to point out violations as if they are news.
Proteins affect gene expression. They can even edit nucleotide sequences. They do not reverse engineer themselves back into nucleotides. There is no reverse translation.
Wasn't that the point of the original blog post?!
Pellionisz said...
... my oft-cited papers
AJ Pellionisz 16 papers 1984-2009; gap from 1993 to 2006. Total citations 62, three publications 2006-2009 11 citations. Neuroscience, the 2009 paper touching on genomics.
A Pellionisz 12 papers 1977-1988. Total citations 538. Three highly cited papers in 1982 (96), 1980 (112), 1979 (112), on neuroscience.
@Pellionisz
Apparently, the field is not swayed by your arguments in "The Principle of Recursive Genome Function". Perhaps you should stop treating you paper as fact?
Extracted from ISI WoS;
Title: The Principle of Recursive Genome Function
Author(s): Pellionisz Andras J.
Source: CEREBELLUM Volume: 7 Issue: 3 Pages: 348-359 DOI: 10.1007/s12311-008-0035-y Published: SEP 2008
Times Cited: 3 (from All Databases)
@cabbagesofdoom
In honeybees and some (many?) other insects, I think that methylation is actually prevalent in the coding sequence.
Being one of the mechanisms of mammalian imprinting, I guess it's quite possible that we too have methylation of coding sequence - I wouldn't say it's only promoters affected, just frequently.
Essentially, like many (all?) 'genome-level' processes outside of translation/transcription, methylation is blind to gene structure (though not sequence). 'Parsing' genes is the job of translational/transcriptional mechanisms. A methylation mechanism simply needs to identify sufficient of the gene - prefixes + exon/intron + suffixes - to achieve the necessary level of control over expression.
The issue is not ideology, nor is [it] entertainment - but a life or death challenge, making obsolete dogmas simply not permitted to stand in the way.
I'm afraid I don't see the manner in which the dogma (or 'junk DNA') presents an obstacle to progress. Yes, the genome can be regarded as a program that acts upon itself via the necessary intermediaries of proteins, created by translation/transcription from genomes. It is tightly regulated, and when that regulation goes wrong we get cancer and other genetic diseases.
But proteins affect this regulation only by influencing gene expression, not by changing the sequence in either the switches or in the coding portion.
DNA sequence -> RNA sequence -> protein -> DNA-as-a-substrate is not the same as DNA sequence -> RNA sequence -> protein -> DNA sequence
The simple fact is that we do not see DNA sequence amended except in the following circumstances:
1) Mutation
2) Recombination
The reasons for this are quite fundamental, and IMO best understood through molecular biology, not informatics.
@cabbagesofdoom
@Allan Miller. {...] it is true, methylation does not violate the Central Dogma as proposed by Crick, and the naive interpretation based on the Watsonified version was violated so long ago that it's just silly to point out violations as if they are news.
Proteins affect gene expression. They can even edit nucleotide sequences. They do not reverse engineer themselves back into nucleotides. There is no reverse translation.
Wasn't that the point of the original blog post?!
Just rereading, and I realise it may not have been clear that my observations about methylation were in response to the preceding post by Dr Pellionisz, not (as it may have appeared) talking to myself!
I am happy not just for Allan Miller in the epitomy of detractor (skeptic, better said, often damaging) blogs to have finally arrived at my conclusion: “Yes, the genome can be regarded as a program that acts upon itself via the necessary intermediaries of proteins, created by translation/transcription from genomes. It is tightly regulated, and when that regulation goes wrong we get cancer and other genetic diseases.” Along with cabbagesofdom that “Proteins affect gene expression. They can even edit nucleotide sequences” the rest is up to those competent in writing software built on algorithms based on valid axioms superseding dogmas. It does not matter much how many Ph.D.-s those have who have ever written a single line of code and in what primary field obtained advanced degrees – since the Beijing Genome Institute deployed about 4,000 software specialists to interpret genomes and their regulation. Since their average age is 26, the vast majority has no Ph.D. at all (college drop-outs are not unusual). What we face is that cancer is likely to go down in history, after chess playing, where computers will beat humans. However, just like in chess-champion HPC, cancer-decoding (recursive) software-algorithms originate from the biological neural networks of the human brain.
For Heleen and The other Jim, the record needs to stand corrected. Google Scholar shows my papers “Pellionisz” cited 1290 times, and my 150 papers (non-public, e.g. classified NASA documents not included) are listed in my bio most with links to full free texts on the web.
Of course I fully realize that many wish -in vain- that “the field is not swayed by your arguments in "The Principle of Recursive Genome Function"” (because cliffs of paradigm-shifts necessitate sharp turns that certain Titanics can not take; this was one reason why Crick in a mad rush in 1956 unfortunately dogmatized genomics for over half a Century, since their Double Helix paper in 1953, by grace of X-rays made by Rosalind Franklin, beating Pauling’s Triple Helix mistaken assumption, was not cited even once for seven years after publication).
Actually, my “Fractal Approach” has taken off even before The Principle of Genome Function manuscript was published. I personally handed the manuscript over to Eric Lander (a science adviser to the US President, first degree in mathematics), who – along with a slew of researchers from both Coasts, rushed their fractal genome cover-article in Science (Oct. 9, 2009) – just weeks after I delivered the concept at the Personal Genomes meeting of George Church in Cold Spring Harbor Lab (Sept 16, 2009).
“Now Rebels are Turning Leaders”; Eric Lander is Director of the $600 M Broad Institute, Eric Schadt (double-degree mathematician) who could not turn Merck into a genome informatics company) has just commenced his Directorship of the $100 M Mount Sinai Institute of Genomics and Multi-Scale Biology (rhymes with “Scale-Free” fractals…) – and Rigoutsos (should I say, a Ph.D. in mathematics?), having left IBM where he struggled to get his “pyknon”-paper published, became director of Genome Informatics at Jefferson (on generous funds by Keck).
@Allan Miller: Sorry, that was my fault. I was agreeing with you and adding general comments in support. Didn't make that clear.
Well Pellionisz... enjoy your martyrdom.
Thnx, "The other Jim":
No pain, no gain. Some people still care.
Pellionisz said...
For Heleen and The other Jim, the record needs to stand corrected. Google Scholar shows my papers “Pellionisz” cited 1290 times, and my 150 papers (non-public, e.g. classified NASA documents not included) are listed in my bio most with links to full free texts on the web.
The record I used was ‘Web of Science’ (seems to be renamed ‘Web of Knowledge by Thomson Reuters), anyway the standard scientific database. Google Scholar gives 168 hits on ‘Pellionisz’, including [citations], but that seems only a very rough database, and the actual citations indicated have to be totaled by hand, as far as I can see.
1 I’ll stick to Web of Science
2 Pellionisz has a good but not eminent track record in Neuroscience
3 The scientific work of Pellionisz is outside anything that has to do with Central Dogma.
As to the link to the Personal Genomes meeting of George Church in Cold Spring Harbor Lab (Sept 16, 2009). : there are presentation slides there. I challenge anyone to make sense of those.
heleen you acknowledge what
Pellionisz said - that he
"delivered the concept at the Personal Genomes meeting of George Church in Cold Spring Harbor Lab"
Your personal opinion about it is irrelevant. His point is that he delivered the concept.
Heleen, you sound churlish.
As to the link to the Personal Genomes meeting of George Church in Cold Spring Harbor Lab (Sept 16, 2009). : there are presentation slides there. I challenge anyone to make sense of those.
Slide 11 - "mapping of arbitrary DNA 'words' yields the Zipf curve given by human languages. "
A curious - and "recursive" :0) - linkback to the Atheistoclast paper along similar lines linked many, many posts ago. There's gold in that thar junk. Maybe. Or maybe natural language is just one method of pulling symbolic sequences at random out of the space of all possibilities, which, done genuinely at random (ie not using an existing symbolic set and usage pattern), also gives Zipf's curve.
http://www.nslij-genetics.org/wli/pub/ieee92_pre.pdf
Pretty remarkable, really, but a bit of a dampener for those seeing 'language' in DNA, junk or otherwise.
Go to 1.
&Miller:
Fig. 11. in my Cold Spring Harbor Presentation recalls an old and failed, arbitrary attempt, duly cited as from Mategna and Stanley (1994), the curves barely resembling the empirical straight line of Zipf-law. The fault was caused by the lack of available definition of the quantum-elements; they used totally arbitrary 3-8 nucleotide "words", cut out without any reason (a bit like Crick admittedly had zero experimental evidence for his dogmatization of Genomics for over half a Century - moreover he admitted that he used the world "Dogma" because he did not know what it meant in the Latin - but sounded good).
You should have directed your attention to Fig. 14, where I used in case of a full DNA sequence Rigoutsos'"pyknon-like repeat elements" (these quanta demonstrably occur with frequencies far exceeding the probability if e.g. the "Junk" was random) and cut through the "genic" and intergenic/intronic regions alike). As shown in Fig. 14., the frequency over rank (log-log) diagram demonstrably follows the Zipf-Mandelbrot Fractal Parabolic Distribution Curve (not the Zipf straight line). Therefore, the DNA is not a "language" but a fractal geometrical code, among others to ensure the kind of enormous compression (of at least 30,000x as found by Barnsley, second perhaps only to Mandelbrot in his expertise in fractals). It is too bad, that neither Mandelbrot took up the fractal approach of genome in his life, and in the latest great book of Barnsley ("Superfractals") he does not seem to have momentary bandwith for it, either.
The "Fractal School of Genomics", nonetheless grows in leaps and bounds, as shown in my Springer book contribution (in press). Not only the science adviser to the US President (Eric Lander) conveyed the "Mr. President, the Genome is Fractal" message, but there are already dozens of workers (whom we know of...) contributing, and many-many positioning to join the fray, either openly or in the largely closed communities of the Beijing Genome Institute, or at SAMSUNG (the first global IT that beat the world by their recent announcement to provide full DNA analytics).
Anonymous said...
heleen
Your personal opinion about it is irrelevant. His point is that he delivered the concept.
Heleen, you sound churlish.
Papers at scientific meetings are up for discussion. If anyone puts slides of a talk freely on the internet, it means the whole world can discuss it. The first duty in a talk is to present it in a understandable way. The first duty of presenting a set of slides on the internet is ensuring that the reader can gauge what they are about. If that is not the case, no one should be surprised at unfavourable comment.
Heleen,
Since you were apparently not invited to Cold Spring Harbor Labs (see the list who were, on the website), just ask questions. Do what the about 300 world leaders did. I am here to discuss science to make a difference in the matter of "Junk DNA diseases".
Lander's one of several people using "fractal" to describe the folded physical shape of the genome, which apparently helps explain why it doesn't tie itself in knots (good thing for us).
@Pellionisz
(these quanta demonstrably occur with frequencies far exceeding the probability if e.g. the "Junk" was random)
Sure, but junk isn't really 'random'. More than half of it consists of defective transposons; the same motifs repeated over and over again with minor variations.
The crucial thing to my mind is that DNA sequence does not just come out of thin air. It is built from template. Every base is there because it was paired (or mispaired) with another base, which was paired with another, which was paired with another ... For simple non-recombinational mechanisms, we just have DNA polymerase doing its stuff for generation after generation.
But with recombination, you can get extension. Transposons recombine existing sequence and extend 'laterally', which extensions then fall into the parent-child copy process. Homologous recombination in meiosis can make misalignment errors that cause a sequence to be lost from one homologous strand and added to the other. Survival is biased in favour of the extended copy.
So the process is broadly one of copy and paste from other parts of sequence. The main exception is telomerase, which does add sacrificial DNA sequence to the ends.
Nonetheless, the fact that this lateral proliferation gives 'nonrandom' junk which shows up in statistical analyses is not necessarily relevant to any functional properties it may have.
Jud said...
Lander's .. using "fractal" to describe the folded physical shape of the genome, .... why it doesn't tie itself in knots ...
Quite useful, no problem there.
What might that have to do with the opposition of Pellionisz to the Central Dogma? Or Pellionisz’ misunderstanding of the Central Dogma?
Sorry that I am so late the conversation.
The Central Dogma of the 21'st century should not occur until at least the weight of the mid-21'st century rolls it down, or it is not the Central Dogma. Whatever rules for the majority of that timeperiod must be considered Central Dogma. Since it is 2011, please let me know how you are so confident what that "Central Dogma" is. We can measure any metric you like, but from my perspective you are not all "wrong" so much as "unknown if correct". Although that Anonymous chap and perhaps Sparc (?) do seem to get the point, as I see it at least. No, not all Anonymous are Anonymous.
Regards, though I will probably not post again.
-M
Jud said...
Lander's one of several people using "fractal" to describe the folded physical shape of the genome, which apparently helps explain why it doesn't tie itself in knots (good thing for us).
Indeed, as shown in the hologenomics website, see link just underneath "Mr. President, the Genome is Fractal!" there is my short essay on the "Lander et al. 2009" Science cover article, showing the 19 authors with Lander, both as Director of the Broad Institute and Science adviser to the US President, providing the impetus to get the Hilbert-curve (1891) on the cover, and duly citing Alexander Grosberg's two seminal articles (while still in Moscow, now at NYU Courant Institue). As cited, Shura conceived the "fractal folding (structure) of DNA" over two decades ago - just as I authored my Cambridge University Press book chapter on "fractal stucture" of brain cells at that time - already invoking that such fractal development assumed (the double heresy) of recursion. That was such a Crick-tabu that nobody had a chance fighting while Francis (whom Jim Watson "never seen in a modest moode") was alive (2004) (BTW, Jim Watson attended - without opposition - the CSHL meeting where I presented my Principle of Recursive Genome Function (specifying fractal iterative recursion), see photo-moniker of my FaceBook page.)
Looking at my animated 3D picture of the Hilbert-curve, breaking the tabu also by Eric Lander, the "knot-free" secret of fractal folding is not only an easy-to-understand requirement for hick-up-free transcription, but reveals the functional sine qua non of the "linear" DNA strand. Looking at my essay two further aspects of the fractal Hilbert-curve are quite remarkable. The importance that the Hilbert-curve is "ultra dense" (in its 2D rendering its fractal dimension is 2.0 - entirely filling the 2D space)is obvious. Less transparent is the transparency of e.g. the rotating 3D Hilbert-curve, that brings any two points of the "linear segment" into minimal distance from one-another. Structure thus becomes a key to recursive function; since by "opening up" the ultra-dense folding, like a leporello, the "first page of the book can be the nearest neighbor of the last pages". The Principle of Recursive Genome Function is, therefore, very strongly substantiated by Eric invoking fractal folding structure. One may wish to still fight the 19 authors, with Lander putting his weight into Phase 2 (analytics) after Phase 1 (sequencing) of the DNA, but the motivation became crystal-clear that detractors of an entirely new age oppose progress for a combination of two factors; (a) they have vested interest in the Old School, (b) May be unable to contribute with mathematics, informatics and most importantly, with software built on valid axioms, superseding dogmas.
Since a rapidly demolished opposition still causes the countless deaths of those suffering from "junk DNA diseases", I will not accept "anonymous" hindrance (that can be exercised forever unpunished), we will see to it that those with documented efforts to hinder progress by named professionals (whose duty is to avoid negligence and serve the best interest of millions if not hundreds of millions of people suffering from "junk DNA diseases") will pay the heavy price they deserve. Death and suffering is no joking matter.
heleen writes:
What might that have to do with the opposition of Pellionisz to the Central Dogma?
I'm sure quite a lot according to Pellionisz.
So far as I can see, absolutely nothing, which is why I mentioned it.
Jud said...
Lander's .. using "fractal" to describe the folded physical shape of the genome, .... why it doesn't tie itself in knots ...
Quite useful, no problem there.
What might that have to do with the opposition of Pellionisz to the Central Dogma?
Heleen said…
I'm sure quite a lot according to Pellionisz.
---
Indeed, any “dogma” should be outright rejected (not “opposed”) by superseding them by valid principles. Fractal (knotless) folding of DNA is obviously useful for smooth transcription – but beyond structure a fractal function (compression, typically by 30,000x) is of the essence since without Nature's compression your genome could not possibly be confined to about half the size of a Windows 7. Think about it! Your biological complexity is less than a rather pedestrian OS??? Those who know anything about basics of informatics never bought the Crick-Ohno informatics-nonsense reducing DNA to its 1.7% (actually, much less, since most of the “genes” are introns). This is why my YouTube was such a success as a Google Tech Talk.
BTW, my contribution by <a href="http://ww.junkdna.com/pellionisz_principle_of_recursive_genome_function.pdf><b>The Principle of Recursive Genome Function</b></a> is to open the floodgates to fractal recursive iteration and other recursive algorithms, superseding by modern science a set of archaic oversimplifications that a contemporary leader characterized as <i>“frighteningly unsophisticated”.</i>
This phrase has been repeated a number of times from comment #2 onwards, and all "Central Dogma is dead" proponents continue to ignore it.
Do proteins reverse-translate?
If yes, Dogma is dead.
If no, not dead yet.
This is the "fossil rabbit in the Precambrian".
Fractal recursive genomes, epigenetics, prions, reverse transcription, transcriptional and translational regulation (regardless of mechanism) etc are not violations of this unfortunately phrased principle.
This whole thread is a demonstration of the original post's point. To quote...
If your goal is to start a revolution in biology then the first thing you have to do is knock down the existing "dogma." It doesn't seem to matter that you are attacking a strawman. But it's a sign that the rest of your agenda isn't very sound."
Amazingly predictive of the Pellionisz's last paragraph on Wednesday, September 14, 2011 8:33:00 PM.
P.S. That link is to the paper that has been cited 3 time, as noted on Monday, September 12, 2011 7:06:00 AM. A revolution indeed.
Pellionisz said something on Wednesday, September 14, 2011 8:33:00 PM, but did not get to the point of why he rejects the Central Dogma.
The question is: do proteins reverse translate / transcribe into DNA? Pellionisz has not said anything about this.
As long as Pellionisz does not make clear why he thinks reverse translation from protein into DNA is feasible (if he thinks that), all the talk about ‘Central Dogma is obsolete (et patati patata)’, or why he thinks fractality has anything to do with the Central Dogma, is less than useless
Heleen appears to be less than a scientist, and the way counts links is highly suspect (not unusual for anonymous detractors). Type into Google "Recursive Genome Function". As of this moment one gets 7,560 hits. "Pellionisz" gets 16,800. My "Principle" (full free .pdf) has been downloaded from my website over 25,000 times according to my weblog.
Pellionisz writes:
but beyond structure a fractal function
Just as I (and I'm sure others) supposed, Pellionisz' repeated citation of Eric Lander re "fractal" is nothing more than Humpty-Dumptying. ("'When I use a word,' Humpty Dumpty said, in rather a scornful tone, 'it means just what I choose it to mean — neither more nor less.'")
Heleen, you don't seem to know what you are talking about. Francis Crick's paper (1970, available full free text from link in "Pellionisz_Principle") never mentions "reverse transcription", nor "reverse translation". Crick did talk about "information" but did not seem to understand either what "Dogma" meant, nor what "genome information" may mean for us, over half a Century later. Crick was famous for his co-discovery of the Double Helix, but could be beaten hands down e.g. in mathematics of biological Neural Nets (he did not have any). Been there, done that. Define what Crick failed to do so.
@Pellionisz
Francis Crick's paper [...] never mentions "reverse transcription", nor "reverse translation". Crick did talk about "information" but did not seem to understand either what "Dogma" meant, nor what "genome information" may mean for us, over half a Century later.
Here we go, then. I have bolded one word, and changed the one that seems to bother some people.
"The central [Rule of Thumb] of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid."
I think mathematicians get far too bogged down in Shannon-this and entropy-that and random-the-other when they see that trigger word “information”. Crick was using it quite informally. He does talk about reverse transcription, and accepts the possibility. He does talk about reverse translation, and rejects it. He simply does not use those terms - but no tap-dancing is required to understand that they are precisely what he is discussing.
Fundamentally, nucleic acids form a template and proteins do not. Nucleic acid templates can specify exact copies (full preservation of the “information”) and can specify amino acid strings when passed to the appropriate mechanism. But peptide chains cannot be ‘read’ in this way – in the cellular environment, they fold tightly and contain many potentially reactive residues - that's why they are good catalysts, but it makes them a useless template.
heleen said...
Pellionisz said something on Thursday, September 15, 2011 9:04:00 PM, but still did not get to the point of why he rejects the Central Dogma.
The question is: do proteins reverse translate / transcribe into DNA? Pellionisz has not said anything about this.
As long as Pellionisz does not make clear why he thinks reverse translation from protein into DNA is feasible (if he thinks that), all the talk about ‘Central Dogma is obsolete (et patati patata)’, or why he thinks fractality has anything to do with the Central Dogma, is less than useless than usefull.
I've seen Pellionisz do a lot of name dropping, but I've not seen any explanation of why he rejects whatever he takes the Central Dogma to be. I've not even seen an explanation of what he takes the Central Dogma to be.
The Central Dogma is about reverse translation from protein to DNA, not about regulation of gene expression by protein transcription factors. And not about fractals.
‘Pellionisz’ gets qbout 16,900 hits on Google, of which the third and fourth are:
http://sandwalk.blogspot.com/2008/11/is-andras-pellionisz-kook.html
http://www.uncommondescent.com/intelligent-design/dna-researcher-andras-pellionisz-gives-favorable-review-to-shredding-of-dawkins-and-talk-origins/
‘Recursive Genome Function’ – Googling that shows that Pellionisz has been very active in many comments threads for a few years. See for instance : http://www.genomicron.evolverzone.com/2008/11/pellionisz-google-tech-presentation/
Who else mentions Recursive Genome Function but Pellionisz?
Anyway, Pellionisz, explain in understandable words (1) what you take the Central Dogma to be; and (2) what the data are that invalidate it.
Pellionisz said...on Thursday, September 15, 2011 10:41:00 AM
Heleen ... counts links is highly suspect
Calling Web of Science 'highly suspect'?
heleen says,
‘Pellionisz’ gets qbout 16,900 hits on Google, of which the third and fourth are:
http://sandwalk.blogspot.com/2008/11/is-andras-pellionisz-kook.html
The title of that article is, Is Andras Pellionisz a Kook?
The answer is "yes" and that really makes Pellionisz angry. He has threatened me with legal action for "slandering" him on Sandwalk." Apparently he runs some kind of business based on his reputation as a scientist and it's embarrassing that Goggle searches come up with an article identifying him as a kook.
Ironically, one of the common characteristics of kooks is the belief that their rights have been violated and that lawyers will be able to prove it in court.
If you follow the link you can watch a very entertaining video of Pellionisz giving a presentation of his ideas. It explains a lot.
Pellionisz himself attracted attention to his Google record on Thursday, September 15, 2011 10:41:00 AM.
Pellionisz says,
Heleen, you don't seem to know what you are talking about. Francis Crick's paper (1970, available full free text from link in "Pellionisz_Principle") never mentions "reverse transcription", nor "reverse translation".
Here's the link to Crick's 1970 paper: Central Dogma of Moleclar Biology.
It was published in response to claims that Temin's discovery of reverse transcriptase overthrew the Central Dogma. The opening sentences of Crick's paper are ...
"The central dogma, enunciated by Crick in 1958 and the keystone of molecular biology ever since, is likely to prove a considerable over-simplification".
This quotation is taken from the beginning of an unsigned article [1] headed "Central dogma reversed", recounting the very important work of Dr. Howard Temin [2] and others [3] showing that an RNA tumour virus can use viral RNA as a template for DNA synthesis. This is not the first time that the idea of the central dogma has been misunderstood, in one way or another. In this article I explain why the term was originally introduced, its true meaning, and state why I think that, properly understood, it is still an idea of fundamental importance.
Technically, Pellionisz is correct. Crick never uses the term "reverse transcription." Instead he talks about RNA --> DNA transfers.
Crick also doesn't use the term "reverse translation." Instead, he says,
The transfer protein --> RNA ( and the analogous protein --> DNA) would have required (back) translation, that is the transfer from one alphabet to a structurally quite different one. It was realized that forward translation involved very complex machinery. Moreover, it seemed unlikely on general grounds that this machinery could easily work backwards. The only reasonable alternative was that the cell had evolved an entirely separate set of complicated machinery for back translation, and of this there was no trace, and no reason to believe that it might be needed.
Judge for yourself whether Crick's non-use of those specific words is relevant or just nitpicking.
@Miller and @heleen:
Miller says:
I think mathematicians get far too bogged down in Shannon-this and entropy-that and random-the-other when they see that trigger word “information”. Crick was using it quite informally.
All above (and plus) admit that Crick did not use either "reverse transcription" or "reverse translation". All admit that Crick mislabeled his tenet as "Dogma" for his (self-confessed) failure to understand what that Latin word meant. Miller now admits (the obvious) that Crick used the word "information" informally
("I think mathematicians get far too bogged down in Shannon-this and entropy-that and random-the-other when they see that trigger word “information”. Crick was using it quite informally").
I am sorry to say that in mathematical theories, including that of genome function, there is no such thing as using words "informally" (i.e. without definitions).
Thus in answering the call by "heleen" "Anyway, Pellionisz, explain in understandable words (1) what you take the Central Dogma to be" my answer is rather straightforward and I hope totally understandable:
From now on we should refer to "Crick's Central Nonsense" - an "informal dogma" (an oxymoron in itself) devoid of any mathematical definition.
For those who wish to understand genome function and to fight e.g. cancer without the benefit of computers (requiring mathematical, software enabling algorithms) I simply wish "good luck" by referring to Eric Schadt's video in Genomeweb with my comment ("andras").
Larry Moran said:
Judge for yourself whether Crick's non-use of those specific words is relevant or just nitpicking.
Pellionisz said:
All above (and plus) admit that Crick did not use either "reverse transcription" or "reverse translation".
Pellionisz prefers nitpicking: very nitpicking to point this out.
Pellionisz said... on Friday, September 16, 2011 2:24:00 PM
Thus in answering the call by "heleen" "Anyway, Pellionisz, explain in understandable words (1) what you take the Central Dogma to be" my answer is rather straightforward and I hope totally understandable:
From now on we should refer to "Crick's Central Nonsense" - an "informal dogma" (an oxymoron in itself) devoid of any mathematical definition.
It was clear from the start that Crick’s Central Dogma had no mathematical definition. It is pretty oxymoronic to think it should have a mathematical definition. Mathematics never had anything to do with it. It is about an observation of cellular chemistry.
Pellionisz still did not get to the point of why he rejects the Central Dogma. Pellionisz has not explained anything.
The question is: do proteins reverse translate / transcribe into DNA? Pellionisz has not said anything about this.
As long as Pellionisz does not make clear why he thinks reverse translation from protein into DNA is feasible (if he thinks that), all his talk about ‘Central Dogma is Central Nonsense’ is misguided. Mathematics never had anything to do with the Central Dogma. Pellionisa represents a classical case of someone from another field not taking the trouble to read up on a new field.
Anyway, Pellionisz, explain in understandable words (1) what you take the Central Dogma to be; and (2) what the data are that invalidate it. And don’t go on about mathematical definitions of ‘information’, as these have nothing to do with it – as should have been clear to all and any from the year zero.
Eric Lander's first degree is in mathematics (Director of the Broad Institute, Professor of Harvard, Science Adviser to the President). Eric Schadt is a double-degree mathematician, Chief Scientist of Pacific Biosciences and now Director of the Mount Sinai Institute of Genomics and Multi-Scale Biology, etc., etc. Isidore Rigoutsos (discoverer of pyknons) is a mathematician from IBM (became director of Genome Informatics at Jefferson).
I am sorry, computers are just flabbergasted if heleen (or anybody) talks nonsense to them - they only understand mathematics (software written based on valid algorithms). Garbage in, garbage out with horrendous expense if the underlying axioms are totally wrong, or even just ambiguous.
I bother to talk to you guys since among my degrees you find both a Ph.D. in Biology and a Ph.D. in Biophysics (as well as Computer Engineering). Thus, I understand why a physicist (Francis Crick) could go totally wrong when he separated physics and biology from mathematics (listen to his
video confession). Unfortunately, in his distinguished career Crick made at least three cardinal mistakes. 1) Put out the Crick's Central Nonsense (that a proper [bio]physicist should have never done), 2) In his late years, entered my field of "biological neural nets" with no mathematics to speak of, 3) Though in his late years (passed away in 2004) he realized that no modern science can do without computers (requiring mathematical definitions), he neglected to clean up his obsolete notion (that was over half a Century old even while Crick was alive, though late in his life he was fully aware that without "computer readiness" his notion that classifies as "System Theory" under Ludwig von Bertalanffy, 1936, would just be discarded as useless).
With all due respect for what he did accomplish, our duty is to clean up after Crick (what his mathematical definition might have been if he would have thought of them at all, etc), but to supersede the obsolete dogmas based on The Principle of Recursive Genome Function - just as I, as a biophysicist have done (with degree in, thus respect for biology). Based on that computer engineering (that I know because of my other, actually first Ph.D.) we can thrust ahead to solve cancer (and other "Junk DNA diseases") using the benefit of awesome computing power.
Dr Pellionisz
(I paraphrase) "I have lots of degrees, some of them even relevant to biology; here are some more people very highly qualified in mathematics and stuff. Listen to us all as we pontificate upon molecular biology, for we are far more intelligent than you mere lab-monkeys".
Whatever; you seem to completely confuse the use of informatics and computation in investigating the patterns in the genome, vs the extent to which the genome itself can be said to be an informatic, informational construct. DNA resembles a computer program in many ways, and is tantalisingly stringy in its arrangement, just like a comms packet. It is also nothing like a computer program, or informational strings, in many more.
But your obtuse stubbornness over the Central [Call-it-what-you-will] is revealing. If everyone in the field says X, and you say Y, it is not always the case that a Kuhnian paradigm shift is just around the corner.
@Miller:
(Paraphrasing him) "Some modern genome researchers are highly qualified in biophysics and mathematics, since this challenge simply can not be met without computers. Those who don't realize this might want to quietly let go the Crick Central Nonsense - or will disqualify themselves"
Note, that Crick was a (bad) physicist with an attitude against mathematics - he was certainly not a "lab monkey" in biochemistry. Twisting whatever that he did not say (properly, but might thought about, improperly or otherwise) will not help postmodern genome informatics, over half a Century later.
My scientific imprinting was by John von Neumann ("The computer and brain") - who passed away just at the brink when he realized that the mathematics of brain function is certainly not the mathematics (logical calculus) that his invention, the computer, was architected upon.
As a biophysicist with cross-disciplinary training and advanced degrees I devoted decades to ferret out the intrinsic mathematics of the brain (biological neural nets) and identified tensor geometry, such that e.g. the cerebellar coordination is clearly understood (see my Tensor Network Theory).
After that accomplishment, I identified the mathematics of genome function as "fractal recursive iteration" (FractoGene) that is certainly not the intrinsic mathematics (Boolean algebra) of the function of computers.
I don't expect many to master tensor and fractal geometry. Some decency would suffice to appreciate those thinking outside of the weird box of Crick's Central Nonsense and Junky "theories" of Ohno on genome function, where the DNA is reduced to 1% of its relevance.
"it is not always the case that a Kuhnian paradigm shift is just around the corner">
Indeed, it is not "around the corner" - but we are in the middle of it. Those who fail to realize this well-documented fact, will continue the Big Genome Letdown of the past decade (billions spent on sequencing with "frighteningly unsophisticated" understanding of genome analytics) and not only will continue wasting more billions, but will be responsible for the death of millions, if not hundred millions of people suffering from "Junk DNA diseases" like cancer.
Detractors may call me a kook, or stubborn (or anything, depending on their level of ignorant malice, up to cyber-libel) - but the genome is fractal and the "arrow model" (of DNA-RNA-PROTEIN) has long reached a dead end. Genome function based on fractal iterative recursion.
I don't expect many to master tensor and fractal geometry. Some decency would suffice to appreciate those thinking outside of the weird box of Crick's Central Nonsense and Junky "theories" of Ohno on genome function, where the DNA is reduced to 1% of its relevance.
In order to think effectively outside the box, it helps to have some appreciation at a fundamental level of what is inside it.
Rebranding Crick's statement of the irreversibility of translation as "nonsense" is plain wrong, for very sound mechanistic reasons.
And there is a fraction of the genome that serves no purpose whatsoever. It may be large or small - I say large - but a decent understanding of the mechanistic basis by which DNA accumulates or is lost seems lacking in your expressed views. Such an understanding is necessary to inform an opinion on the likely percentage of functional DNA.
Lack of mechanistic understanding seems a common enough trait of the mathematician. "Decency" might persuade one to understand molecular biology and evolution a bit better, because it is relevant to putting Crick and Ohno in their proper place. Then there's Crick again, with Orgel, and Doolittle and Sapienza, on selfish DNA and levels of selection - very relevant to "junk". And Kimura on models of neutral substitution. It's all relevant to an understanding of the genome. If one wants to be viewed as something other than a crank, that is.
@Miller:
"In order to think effectively outside the box, it helps to have some appreciation at a fundamental level of what is inside it.
Yes, inside the box of the Old School "understanding" there is lots of good data and some fundamental basic assumptions that Eric Lander (Science Adviser to the President) told off the entire NIH leadership as "all wrong".
The first decade since Sequencing of Human DNA is chalked up as the "Great Genome Letdown".
You know what? Instead of calling names (of Lander, Schadt, Rigoutsos, Mattick, me and other pioneers etc, etc) try to understand some basics in the sciences, as I have done through my Ph.D.-s in Computer Technology, Biology, Physics. For instance, there is no such thing as "negative evidence". Your statement "there is a fraction of the genome that serves no purpose whatsoever." is totally absurd. Anything that you are not sure if it serves a purpose may very well have one - beyond the point of your present (how should I say?) very limited understanding.
Fractal recursive iteration is a theory (FractoGene) with software-enabling algorithms will shine - of course unless you or some more mathematically minded person comes up with a theory that will beat FractoGene.
The Old School is a generally recognized Failure. Do you have anything of your own to show? Time to put up or shut up. Badmouthing Lander and an exploding New School does not seem to be a very good idea.
What are your credentials, anyway?
Badmouthing Lander
Criticizing your misrepresentation is not the same as criticizing the person whose ideas you're misrepresenting.
For instance, there is no such thing as "negative evidence". Your statement "there is a fraction of the genome that serves no purpose whatsoever." is totally absurd. Anything that you are not sure if it serves a purpose may very well have one - beyond the point of your present (how should I say?) very limited understanding.
(How should I say?) shove it up your arse! Of course there is a fraction of the genome that serves no organismal purpose. The obvious way to “prove the negative” is to chop a chunk out. This has been done with no discernible effect on organismal fitness, though obviously not to the extreme level of >95% excision. But ... there demonstrably is a fraction of the genome that serves no purpose whatsoever.
There are many disabled pseudogenes. They degenerate too rapidly to be a serious contender for an organismal reservoir of future adaptative change. SINEs and LINEs are not there for the benefit of the organism – they are genetic parasites. They betray a historic pattern of infection and disablement, symptomatic of a battle between the element and the wider genome, and are internally equipped for disruptive activity, rather than externally promoted. These facts make viewing them as organismal constructs for general benefit just perverse. We must always accept the caution that SOME of these may have actually been ‘domesticated’, and serve an organismal purpose. But your appeal to the vague – “Anything that you are not sure if it serves a purpose may very well have one” – is not convincing argument for a fully-functional genome, down to the last base. YOU prove it; don’t just have a pop at me because I can’t be categorical about the lack-of-function of any particular sequence you may throw at me out of GenBank!
If your much greater understanding permits you to give me the ‘organismal’ purpose of LINEs and SINEs, then let’s have it. You may like to explain why their architecture is entirely consistent with genetic parasitism, and entirely inconsistent with organismally-controlled mechanism, while you’re at it.
Badmouthing Lander and an exploding New School does not seem to be a very good idea.
I never said a word about Lander. If I am badmouthing anyone, it is just you. I think you are too in awe of your own intellectual capacity to admit to any possibility that you may lack depth in certain areas. This will impede your ability to get your message through to people who do understand those areas. It's your choice as to whether that matters.
What are your credentials, anyway?
You play this game in every post you make. "Look at all my degrees. Look at this person's qualifications, and that." Yawn. I have a degree in molecular biology. That's it. Papers published: none. Citations: none. I never wrote up my PhD. Presumably, then, I am incapable of rational thought.
@ Miller:
I never said a word about Lander. If I am badmouthing anyone, it is just you.
That just shows your lack of character. Lander and I (plus rapidly swelling ranks of scientists who are fed up with the "all wrong" fundamental assumptions of Old School Genomics) are saying the same - stop your bloody nonsense. Of course, you shy away from badmouthing the Science Adviser to the President of the USA.
What are your credentials, anyway?
I have a degree in molecular biology. That's it. Papers published: none. Citations: none. I never wrote up my PhD. Presumably, then, I am incapable of rational thought.
No, the capability might exist. You just have to prove it, like others have done so, to be taken seriously.
Hmmm. Scooting straight past the substantive part of my post to get to the slanging and credential-waving. OK, then, I’ll assume you have no answers.
(Miller) I never said a word about Lander. If I am badmouthing anyone, it is just you.
(Pellionisz) That just shows your lack of character. Lander and I [...] Of course, you shy away from badmouthing the Science Adviser to the President of the USA.
If the Science Adviser to the President of the USA talked bollocks on the internet, I might have a beef with him. But he seems an eminently sensible chap. I enjoyed the talk you linked.
He pronounced “All wrong” over a slide of the “2000” position, wherein we had a gene count of 35,000-120,000, a small proportion of regulatory sequence vs protein coding, and relegation of selfish DNA to an almost exclusively parasitic role. And the equilibrium globule turns out to be an incorrect model of genome folding. Yep – all wrong! Turns out there are c21,000 genes. Conserved non-coding sequence is much bigger than thought – like, a few percent rather than a fraction of one percent. Another ‘paradigm’ bites the dust. Selfish DNA can become involved in gene regulation and stop being selfish. Wow. Turns out this HGP wasn’t such a waste of money after all! We learned stuff, and developed some mind-blowing techniques along the way.
But, besides using that word “fractal” – in a geometric sense, not the recursive DNA->RNA->protein->DNA->RNA … way you espouse, I saw nothing to justify your annexing him as the establishment figurehead of your revolution. Has he ever cited you?
“The genome is fractal, Mr President.”. “Fractal, you say? Gosh. Well ... that sure is something.”.
I'd suggest the efficient compression of the eukaryotic genome is one of the reasons so much of it is junk - evolving an efficiently readable compression mechanism reduces the pressure in the direction of genome economy. And, arguably, early infestation with junk may have selected for optimal 3D structures that can get to the diamonds without having to dig through the dirt, creating a niche for further junk.
Of course, you shy away from badmouthing the Science Adviser to the President of the USA.
...while you do not shy away from using his name to try to lend support to your speculations, when no such support actually exists.
Fractal geometry of folding (Lander and others) and "fractal" genomic code (you) have no intellectual or logical relation to each other.
@ Miller (and some pseudoname):
Lander says at 44:20 of his YouTube I cited (I am glad you liked it) "it is all wrong", where the obsolete label of "transposons" was also displayed "Parasites, junk". Most leaders (Lander, Collins, Venter, Church, Schadt) openly assert that "Junk is anything but". While these giants don't shy away from at times viciously criticizing one-another (Lander was called Slander by Venter, who also called Collins "a government administrator"; while Venter in turn was called Hitler by Watson, etc, etc), they all stood on very strong legs of accomplishments.
It is, therefore, moronic if e.g. calling "all wrong" of "transposons as junk" is not attacked from the sidelines by bloggers with negligible contribution or by blog owners inept in mathematics - just because of fear of power; e.g. Collins as Head of NIH can cut off grant support of even tenured professors in Toronto.
Now that Junk is out, Crick's Central Nonsense is shredded and Fractals are in, I encourage all here to spend as many decades with tensor- and fractal mathematics of biological systems as I did. (Lander did not spend much, "borrowed" Grosberg's 20 year old concepts that Shura published in several papers while still in Moscow). Miller's basic training in molecular biology, I am afraid, may not help him much to become a trail-blazer in fractal compression as it appears in genome informatics (I would refrain from commenting on his math). Likewise, if no-name does not see relation of fractal structure and function does not at all mean that there is none (actually, I provided a pointer to my essay linked to the rotating 3D Hilbert-curve to show the relation; but admittedly the intrinsic mathematics of genome function is beyond some laypeople).
Lander's YouTube is 44:20 in entirety. The "all wrong" statement is at 9:43, the fractal Science cover is shown at 16:45 and the "close functional distance" (essential for Fractal Recursive Iteration, AJP) is uttered and displayed as "fractal" at Lander's 18:16
Likewise, if no-name does not see relation of fractal structure and function does not at all mean that there is none
:-) It happens to be my first name. Your conclusion that I was using a pseudonym appears to be as perspicacious as your genomics.
- Of course structure and function are related. One doesn't need animations of Science magazine covers to understand that. What I thought I discerned in your statements was a claim that Lander supports a fractal "code" within the genome *sequence*. Do you wish to withdraw any such claim, or state clearly that any implication I or others drew of such a claim was a misunderstanding on our part?
Miller's basic training in molecular biology
[...]
(I would refrain from commenting on his math)
That's good - I'm not sure I have used any, so you wouldn't have a great deal to go on (just to save you the bother: it's shit).
Likewise, if no-name does not see relation of fractal structure and function does not at all mean that there is none (actually, I provided a pointer to my essay linked to the rotating 3D Hilbert-curve to show the relation; but admittedly the intrinsic mathematics of genome function is beyond some laypeople).
Truly, you are a born educator; a natural communicator!
I'm not sure why you waste your time with no-math bloggers or intellectual gnats on the internet, to be honest. Still, the Hilbert curve relies upon 3D structure - geometry; physical displacement of genome domains in space - while your recursive nested DNA-to-more-DNA-to-more-DNA transcriptive/translative/something-else-ive pathway has nothing to do with spatial orientation in mechanistic terms, even if folding and recursion are mathematically related. I confess, I don't get it either. You think that's our fault, don't you?
@Pellionisz Lander's YouTube is 44:20 in entirety. The "all wrong" statement is at 9:43
Yes, that was the point I addressed in my preceding post. But where you characterise it as him "telling off" the NIH leadership, I see it as delivered with a knowing chuckle, to which the audience responded in kind. And, as I say, the things we were wrong about have been refined in degree only - except, perhaps, the role of transposition.
We can be legitimately surprised at how much transposon sequence there is, with signature conservation, represented in coding and regulatory sites. Due to reading frame shift and sense/antisense insertion, the same transposon base sequence can generate up to six different peptide sequences, and produce mutations of a different character to the SNP/recombinational-slippage models.
So yes, just like beneficial mutations, there can be beneficial transpositional events. But what are the rest doing? About half of Alus are found in or near coding regions. The rest are not. There is a likely identification bias here, because organism-functional elements will be preserved by organismal selection, while others will degrade. The existence of transposons donating functional sequence to genes does not mean that the many elements we find between them (and the many more that may have degraded beyond recognition) exist in order to donate functional sequence at some future point, or are kept as honoured ancestors because they sired functional insertions at some point in the past. Unless and until a sequence becomes functional, at a locus, then it is junk, just as scrapyard cars contain junk parts till someone uses that part. It is simply a provisional matter of classification.
@ Miller:
I'm not sure why you waste your time with no-math bloggers... the Hilbert curve relies upon 3D structure - geometry; physical displacement of genome domains in space - while your recursive nested DNA-to-more-DNA-to-more-DNA transcriptive/translative/something-else-ive pathway has nothing to do with spatial orientation in mechanistic terms, even if folding and recursion are mathematically related. I confess, I don't get it either. You think that's our fault, don't you?
Very profound questions. I am a biophysicist, meaning that my love is biology (love can not be anything else :-) yet I realized from examples of Schrodinger, von Neumann, Wiener, McCulloch-Pitts (and yes, lately from Eric Lander) that the tools of (bio)physics are mathematical - without them no true understanding of biological "system theory" could ever exist. This is the point where I most respectfully but totally disagree with Crick (who, as a physicist failed to appreciate mathematics).
Lander's first degree in in math (he fully realizes that the oft-misapplied slogan "cracking the code" is nonsense as long as the sequences are only revealed but not understood; Broad employes a professional cryptographer mathematician to help). It was correctly noted that Lander was not the first author of the fractal Science cover paper. Erez-Lieberman, a brilliant young biochemist was the first author - who deployed means of biochemistry to support the paradigm-shift. (Given his unbelievable youth, I doubt that he had much - if any - training in fractals).
To paraphrase, astronomers did not go "out of business" when it turned out that they have to cope with the paradigm-shift that the Universe does not rotate around the Earth. They "only" had to start looking at the same sky in an entire different manner. (They did, eminently successfully.)
If my love would not be biology, I could not care less is she was brutalized e.g. by talking about her "data compression" devoid of math.
The shining example of Erez-Lieberman shows that once biologists (e.g. biochemists) let go of obsolete Dogma (very strange for a blog with a majority of atheists...) could actually do much better than badmouthing those with guts to promote postmodern genomics by means of paradigm-shifts.
It is certainly not the "fault" of those whose forte is not in math. I doubt very much that Erez-Lieberman knows much about math (does he know the fractal dimension of the Hilbert-curve in 2D or 3D?). Still, by embracing Grosberg's paradigm-shift he could contribute as a biochemist infinitely more than those ad nauseam sticking with obsolete dogmas of Crick-Ohno, with their nonsense flying in the face of basics of informatics, causing an over-half-a-Century hindrance to Genomics, and directly causing misery and death of hundreds of millions of people suffering from "Junk DNA diseases" like (fractal) cancer.
@Pellionisz
You didn't answer either question.
1) Why is DNA's 'fractal' physical geometry an endorsement of your ideas on recursion? Proteins are fractal too - but then, so is my foot. Many more gene-gene interactions do not rely on physical proximity than do - communication between homologues and "chromosome territories" within the cell, or via the bloodstream and nervous system without.
2) If junk DNA is dead, how do we account for function in every one of (to take one example) the 1.1 million copies of Alu we possess: 10% of the genome? Inserted sense or antisense into protein coding, one sequence can donate up to 6 different peptide sequences, or STOP/Start/exon-intron boundary, and engender change. But just sitting there in intergenic space - 500,000 inactive copies, 150 million bp - junk, surely?
1989: Pellionisz'"Fractal Recursion" (published as a chapter of Cambridge University Press book where he is an Editor) is double heresy as it violates both the Crick Central Dogma and Ohno's Junk DNA axiom. Let's cut his NIH funding.
2002: Pellionisz "FractoGene" can only be officially recorded as a USPTO filing, since the ruling establishment would not pass peer-reviewed publication of a paradigm-shift violating principal dogmas.
2007: NIH releases ENCODE results, Collins issues call "the community of scientists will have to re-think long-held beliefs".
2007 Dec/2008: Pellionisz can publish his peer-reviewed "The Principle of Recursive Genome Function" - popularizes in 2008 Google Tech Talk YouTube.
2008: Within days of the YouTube release, a moronic badmouthing campaign commences...
2009: ...but also Pellionisz' Principle is presented to Cold Spring Harbor, weeks before the Science cover article by Lander et al. on Fractal Genome appears.
2010: Lander starts telling NIHGS that fundamental assumptions of Genomics are "all wrong".
2011: The moronic blog, after a mere half-of-a-thousand blog entries can no longer uphold Crick's Central Nonsense, and even badmouthing bloggers with minimal education start thinking about the connection between fractal structure and function of DNA. A former badmouther now demands education for the next steps since "Junk DNA is dead".
2012: Pellionisz publishes book chapter in The Cerebellum (where he is an Editor), a Springer handbook on "Recursion in the Cerebellum: A Geometrical Unification of Neuroscience and Genomics".
It took less than a quick quarter of a Century for a paradigm-shift to prevail...
Genome interpretation hyper accelerates with pioneering deployment of fractal recursive algorithms, making the Industrialization of Genomics sustainable with investments in Sequencing and Analytics balanced.
A former badmouther now demands education for the next steps since "Junk DNA is dead".
You mean me? I demand a retraction - I am not a "former badmouther"; my badmouthing is very much an ongoing matter!
Another rambling post from you once again failed to say anything substantive.
If junk DNA is dead, how do you account for function in 1.1 million Alus? Simple question.
Since physical proximity is not the primary determinant of gene interactions, what links physical proximity (the Hilbert curve) to "recursive genome function", beyond the magic word "fractal"?
Ohno and Crick remain undented. Unless you can express yourself in terms that uneducated blog-monkeys like me can understand, stop wasting your time on blogs.
@ Allen Miller
There is a likely identification bias here, because organism-functional elements will be preserved by organismal selection, while others will degrade.
True, but there may be a functional reason as well. Transcription requires opening up the DNA sequence for it to occur. If the DNA is open more, there is more opportunity for a retro-transposed insertion. Stuff buried under a blanket of histones will be less available to the inserting sequences.
I am not a "former badmouther"; my badmouthing is very much an ongoing matter!
Talking nonsense; Ohno and Crick remain undented (both their bodies and mistakes have long been dead as a door nail) is not badmouthing - just bad judgement. Once you recourse to badmouthing, you'll also be disqualified.
Regarding your unsolicited advice Unless you can express yourself in terms that uneducated blog-monkeys like me can understand, stop wasting your time on blogs., I should point out that even self-labeled uneducated blog-monkeys occasionally need to keep up with science literature, or time, indeed, will not be wasted on them.
As for Alus, read e.g. this fresh reference by V. Lunyak et al. Victoria (a Founding Member of the HoloGenomics Society) will be glad to mail a full .pdf upon request.
For full functional proximity, the linear transcription of DNA mislead most naive thinkers that genome function must therefore be also linear. Not so. The massively parallel fractal iterative recursion, since the interaction is molecular, requires "nearest neighbors" for parallel reading (for the IT-savvy, see the serial architecture of conventional CPU-s in contrast to parallel data-flow machines of e.g. FPGA-s or GPU-s).
It is extremely surprising that Pellionisz (despite multiple degreed) is not able to distinguish molecular and chemical fact from spun out fiction.
None of the comments Pellionisz made have anything to do with the central point first explicitly made by Crick: reverse translation has never been observed.
It is extremely surprising that Pellionisz (despite multiple degreed) is not able to distinguish molecular and chemical fact from spun out fiction.
None of the comments Pellionisz made have anything to do with the central point first explicitly made by Crick: reverse translation has never been observed.
For a "no name" ignorance is not surprising at all that Crick entitled his (admittedly unsupported) fiction "Central Dogma of Molecular Biology" - and he never wrote explicitly about "reverse translation". Crick referred to "sequence information". The irony is, that Crick was a physicist, thus familiar with Shannon's Information Theory - but suspected that there may be more to "sequence information" beyond the 2-bit string of A,C,T,G bases. (Crick's knowledge on methylation and chromatin modification, impacting "access to sequence information" was understandably immature.)
In his 1970 “correction” his Fig. 1. “arrows show all the possible simple transfers…” but just above his “reduced” Fig. 2. he says “Now if all possible transfers commonly occurred it would have been almost impossible to construct useful theories. Nevertheless, such theories were part of our everyday discussions. This was because it was tacitly assumed that certain transfers could not occur. It occurred to me that it would be wise to state these preconceptions explicitly.”
What appeared to Crick half a Century ago as a “good idea” (to stiffle by pontification possible theories) is now plainly untenable. A leader said lately “our concepts of genome regulation are frighteningly unsophisticated”. It is imperative that unsupported preconceptions are superseded after half a Century delay by The Principle of Recursive Genome Function.
@Pellionisz: I've just read your article. I must confess that I don't really get your point. It seems to be largely attacking very old ideas, whether they are the correct definition of "the central dogma" or "junk DNA" or not. Irrespective of definitions, no one would argue that proteins do not influence gene expression (and replication) nor that *all* non-coding DNA is "junk".
No one would argue that "information", when not restricted to sequence information, flows from nucleotide to protein AND protein to nucleotide. Transcription factors and the histone regulation are not new concepts nor controversial ones. More importantly, they pre-date the ENCODE project.
In your article you keep referring to "pre-ENCODE" versus post-ENCODE (or even "PostGenetics"?!) - can you please explain what discovery of the ENCODE project is so game-changing and how this relates to Recursive Genomics? Is it simply that much more non-coding DNA appears to be expressed than we thought? (Assuming it is not an artefact.)
Ironically, the biggest revolution of recent times, exemplified by ENCODE, is nothing to do with "Central Dogma" violations of protein -> nucleotide. It is the recognition that RNA does a lot more gene regulation functions (miRNA etc.) that were previously assumed to be performed by proteins. This might increase the nucleotide -> nucleotide information transfer - and definitely decreases the amount of functionless junk by a small amount - by I don't get how it leads to conclusions of a "fractal genome".
It is also worth remembering that there is always DNA, RNA *and* protein (and lipids and other metabolites) in any cell, so any linear flow of information is meaningless, unless restricted to the specific flow of sequence information (replication, transcription and translation).
It is extremely surprising that Pellionisz (despite multiple degreed) is not able to distinguish molecular and chemical fact from spun out fiction.
None of the comments Pellionisz made have anything to do with the central point first explicitly made by Crick: reverse translation has never been observed.
It has already been explained to Pellionisz that his insistence Crick did not use the term 'reverse translation' is nothing but nitpicking, denying the obvious content of Crick's remarks. Crick referred to molecular processes, not to information in any mathematical sense. This is clear to about everyone but Pellionisz.
@Pellionisz: Sorry. Just spotted a major typo in my last comment...
> No one would argue that "information", when not restricted to sequence information, flows from nucleotide to protein AND protein to nucleotide.
This should, of course, be that no one would argue that this bi-directional flow of (non-sequence) information does NOT happen! (I think this was clear from the context but sorry for any confusion.)
I too spent time reading the posted paper, and add me to cabbageofdoom and heleen's comments.
The paper provided lots of historical references, but failed to interpret them properly much of the time. Including paragraphs that were directly quoted. It was abundantly clear, that the information flow referred to, time and again, was sequence-to-sequence information. Not "information" in a more general mathematical usage.
It's all never terribly clear at any point, unless I missed some sort of succinct explanation at the end of the paper, what exactly this fractal, recursive genomics theory actually IS, why it is different, and what it offers. There appears to be a hell of a lot of excess verbiage and dense mathematical discussion that never seems to really describe much of anything, at least not in a clear and concise manner.
Colour me shocked as well that the paper is published in a journal for which most of the article is incredibly off topic (except that an analogy of neural growth is shoehorned in) and that the paper went from being received to accepted in about a week.
Obviously thorough and appropriate peer-review was lacking...
As for Post-ENCODE genomics, bunch of bullshit. There is a hell of a lot of evidence, discussed on this blog and elsewhere, that much of ENCODE's findings were a)overhyped and b)artefactual. Direct RNA-Seq based experiments are much better suited to asking the sorts of questions ENCODE wanted to ask, and don't show the same pattern of global transcription and activity of the human genome.
After over half-of-a-thousand blog entries, no-names and those yet to write their first Ph.D. thesis have started to actually read The Principle of Recursive Genome Function. (How could they quote the paper if they have not read it till now - let alone never wrote a paper of their own?)
By admission it is clear that the algorithm of fractal iterative recursion is yet to be understood (but the current emerging generation will soon claim that "everybody - especially them - always thought that the genome was fractal").
For now, some decency will suffice "not to bite my finger, but look where I am pointing", drop twisting the words ("reverse transcription") that Crick never said (yes, he could have thought about a myriads of things but they don't matter if he elected to put out dogma instead of definition).
For the select few who wonder "how to put it all together" go back to study Schrodinger and Shannon to learn what "information" was for them, how Crick could never master math (though he was a physicist...) - and work Genome Informatics as it is meaningful for us, half a Century later.
"Papering over" the paradigm-shifts Crick and Collins (originators of Central Dogma and ENCODE) themselves declared, will not work. Read again their statements (that I quote in my Principle paper for The Central Dogma and ENCODE, respectively):
If it were shown that information could flow from proteins to nucleic acids, he said, then such a finding would “shake the whole intellectual basis of molecular biology” (17, p. 563). (Quote from Darden 63, emphasis added AJP)
Upon publication of the results of project ENCODE, a four year research effort led by the US Government, its architect issued a mandate: “the scientific community will need to rethink some long-held views”.
They issued the mandate - I am just following up on their unfulfilled rhetoric. The better part of your generation will shore up - "Junk DNA" and "Central Dogma" relics will soon fetch a yawn (5, not 500+ entries) in view of the perspectives opened up by fractal recursive algorithms of genome function.
Pellionisz: There are direct quotes in your own paper where "sequence to sequence information" is specified. Not "Information" in the sense of Shannon and other Information Theoreticians. So why do you keep twisting it around in order to try and show that Protein-DNA interactions violate that very specific definition for information transfer.
BTW, good job denigrating people at different parts of their academic career tracks as if they have nothing worthwhile to add to the discussion. Man am I glad none of the senior professors who I feel privileged counting as mentors to me ever talked that way.
Instead they hold up the work of their trainees (or the trainees of others whom they work with) as examples ans foster our intellectual development. And many of them are scientists who have "cut against the grain of conventional scientific wisdom" without falling into kook territory.
@Pellionisz: Sorry to disappoint you but I have a PhD in Genetics and a couple of dozen (rigorously) peer-reviewed publications under my belt. I have reviewed numerous papers and worked upstairs of the Shannon Institute - I use entropy and information theory in my own work and while, admittedly, not a mathematician, I understand what it is. I program and make use of recursion. None of this makes your paper or enigmatic references to fractals and recursion make any more sense.
My PhD supervisor always told me that if someone with the appropriate background doesn't understand your paper then you, as author, have to take the lion's share of the blame. Papers are about communicating effectively. If no one understands what your point is, this suggests that you need to explain it clearer. The way to explain it clearer is not by repeating/quoting the same sentences that people took issue with in the first place.
To be honest, I don't really care what "The Central Dogma" is. I care about the reality of biology. Does reverse translation happen? No. Do proteins regulate gene expression and chromosome structure? Yes. Does signalling "information" pass from protein to protein and protein to nucleotide? Yes. Does this take the form of sequence information? No. Is all non-coding DNA "junk"? No. Is all "junk" DNA functionless? No. Is a large fraction of the average eukaryotic genome still functionless "junk", as far as we can tell? Yes. Is any of this particularly new or controversial? No. Does any of it lead to the conclusion that the genome is fractal or recursive? Explain what this means, with biological examples if possible, and perhaps we can decide.
My instinct based on everything I know about gene regulation, cell signalling and recursion, is "no". (Unless by recursion you mean self-replication, which is recursive in some sense.) The onus is on you to convince us otherwise. It is not our responsibility to try and make your game-changing theory make sense. Currently, your theory opens up no new perspectives because no one cares because it makes no sense. It's just words. If you really thought there was something in it, you would spend much more time trying to explain its evidence and ramifications and much less time insulting the academic credentials of those who disagree with you and/or don't understand your proposal.
I have a PhD in Genetics ... I program and make use of recursion. ... I don't really care what "The Central Dogma" is.
Great - the debate on dead-as-a-door-nail-"Central-Dogma" is finally over. Goodbye Central Nonsense!
I look forward to looking up your papers utilizing recursion (presumably in relation to genome function). References and/or links (as I have provided) would help our scientific communication in regular means.
@Pellionisz: Well, I am flattered that you treat my comments here with the same rigour, care and attention to detail as the scientific literature of the past 60 years. (Selective reading/quoting and failure to address many elephants in the room.)
Bad news, though: reality is not determined by debate. You can play your funny word/quote games and redefine terms all you like but unless you can demonstrate some link to actual reality, no one will care.
In fact, your treatment of The Central Dogma now makes me wonder whether your "recursive genome function" is actually something very old and simple but just called something else. Until you define it clearly, I guess we'll never know. (It certainly isn't fractal without some tremendous unusual definitions.)
I'm off to use recursion (where appropriate) in my programming, but not (where inappropriate) in my genome function.I doubt that we will have much scientific communication, though, as you do not communicate science. References and links should be used to support your ideas and statements, not replace them.
Pellionisz said...
.. started to actually read The Principle of Recursive Genome Function.
That article is irrelevant to the subject under discussion.
drop twisting the words ("reverse transcription") that Crick never said
Crick said the content: no reverse translation. He did not use the actual word, but to focus on that is nitpicking. AND: the Central Dogma is about reverse translation, NOT about reverse transcription. Pellionisz should pay attention.
Pellionisz should do better to read, to READ and UNDERSTAND, what CabbagesofDoom writes. There is the real science of the subject. That is the reality of biology. Pellionisz has as yet to show he understands the reality of biology.
After over half-of-a-thousand blog entries, no-names and those yet to write their first Ph.D. thesis have ..
That is gratuitous offensiveness by Pellionisz. In a debate by blog comment it does not matter two hoots who anyone is or what academic grade one has. It is the quality of the argument and the knowledge shown that counts. Up to now, the quality of the argument or the knowledge shown is not with Pellionisz. Pellionisz seems not to have grasped the major findings of molecular biology. –DG and Cabbages-of-Doom do much better.
Pellionisz
Missed this, but worth a belated comment:
As for Alus, read e.g. this fresh reference by V. Lunyak et al. Victoria (a Founding Member of the HoloGenomics Society) will be glad to mail a full .pdf upon request.
“Inhibition of activated pericentromeric SINE/Alu repeat transcription in senescent human adult stem cells reinstates self-renewal.”
"Upregulation of Alu retrotransposon transcription upon ex vivo aging causes nuclear cytotoxicity associated with the formation of persistent DNA damage foci and loss of efficient DNA repair in pericentric chromatin.
[...]
“Our results demonstrate that the cytotoxicity of induced Alu repeats is functionally relevant for the human adult stem cell aging. Stable suppression of Alu transcription can reverse the senescent phenotype,”
You are arguing that the function of Alu is to cause DNA damage? That is an eccentric reading of the term ‘function’ IMO. I should also note that the pericentromeric region referred to is a narrow part of the chromosome; Alus appear all over the place. I would suggest that the existence of an effect (a “function”, in a very broad reading of that word) does not explain more than a fraction of the 1.1 million Alus we possess. My point is not that no Alus do anything, but that most Alus do nothing. Like Creationists, you have trouble with the distinctions between approximate quantities such as “some”, “many” or “all”.
@ Allan Miller
My point is not that no Alus do anything
It is great that within three short years since The Principle of Recursive Genome Function we succeeded to eliminate the very issues of "Central Dogma" and"Junk DNA".
As for Alus (the "junkiest of all junks") it is nice to agree to an agenda of finding out what (any percentage, rounded properly or not) is actually doing. While Victoria needs no help for interpretation of their findings, I am happy that we are on the right course of looking at them (instead of overlooking them).
I don't think the role of those "non-coding DNA" that are already found to be functional is a "numbers game" (but is a theory-game). I let you and Victoria to fight her thesis out.
In my Cold Spring Harbor presentation (2009) I showed that the known "run" that causes Friedreich Spinoceebellar Ataxia (often a lethal disease) is in the middle of an intronic Alu-segment. The "run" is a fractal defect that disrupts regulation.
Anyone should be free to publish their theoretical and factual arguments of what any part of a fractal genome is doing. Since it does not seem overly meaningful, you would not count the numbers of pixels with various colors in a Mandelbrot-set to arrive at Z=Z^2+C, would you?
@Pellionisz: please explain what the (repetitive element) "fractal" adds to your last comment? It makes much more sense without using that word. (And also nicely sums up the efforts of bioscientists all over the world.)
Pellionisz said...
It is great that within three short years since The Principle of Recursive Genome Function we succeeded to eliminate the very issues of "Central Dogma" and"Junk DNA".
It is absolutely astonishing to see Pellionisz' grasp of fact.
@ some no-name
It is absolutely astonishing to see Pellionisz' grasp of fact.
The peer-reviewed science paper of The Principle of Recursive Genome Function may be too difficult for some novices to understand fractals.
However, the 12,296 views of the popular YouTube and so many gigabytes of downloads from my sites document that the message is sinking in nicely.
By the way, how many times was Gregor Mendel's seminal work cited in the first 35 years after publication? (The answer is 7).
Pellionisz said...
It is great that within three short years since The Principle of Recursive Genome Function we succeeded to eliminate the very issues of "Central Dogma" and"Junk DNA".
Given that both the 'Central Dogma' and 'Junk DNA' are doing very well thank you, it seems if any eilimation was don, it was the Principle of Recursive Genome Function - that no one but Pellionisz has recognized as a principle.
Pellionisz says,
The peer-reviewed science paper of The Principle of Recursive Genome Function may be too difficult for some novices to understand fractals.
However, the 12,296 views of the popular YouTube and so many gigabytes of downloads from my sites document that the message is sinking in nicely.
I've viewed that video at least three times and I've sent many of my readers to the YouTube site [Is Andras Pellionisz a Kook?].
Those 12,296 views may not mean what you think they mean.
On the other hand, you're probably correct to assume that some sort of message about you is sinking in nicely.
Anonymous said Aug. 26. (it is likely to be denied that he was banned for this lucid message …):
Moran goes to great lengths to denigrate the integrity of the person…This is absolutely part of the Moran shtick and he does it again and again.
Cabbagesofdoom concluded:
I don't really care what "The Central Dogma" is. I care about the reality of biology...
Allan Miller concluded:
My point is not that no Alus do anything...
Larry Moran:
… some sort of message … is sinking in nicely.
I say:
From the 12,304 views of my YouTube - (he would probably have to view it not three, but a dozen more times to barely start understanding informatics, lessons sank in for all):
True scientists work hard all over the World towards an algorithmic (software enabling) understanding of hologenome regulation, to save millions, if not hundreds of millions from "Junk DNA diseases".
Dogmas are swept to the side, to share the appropriate company of The Flat Earth Society.
Detractors of breakthrough principles joke around, but are unable, even through 554 posts, to formulate any scientific argument pertaining to mathematics, as they admitted to their daughter's judgement (of inability to comprehend math). Instead, detractors engage in ad hominem-s, again and again.
Evolution is probably correct in natural selection. The DNA of the Central Dogmatist may well be 98.7% Junk.
Not so for the rest of us.
Allan Miller wrote
My point is not that no Alus do anything […] you have trouble with the distinctions between approximate quantities such as “some”, “many” or “all”.
Pellionsz responded
“It is great that within three short years since The Principle of Recursive Genome Function we succeeded to eliminate the very issues of "Central Dogma" and"Junk DNA".
As for Alus (the "junkiest of all junks") it is nice to agree to an agenda of finding out what (any percentage, rounded properly or not) is actually doing.”
Your PhDs appear to have been obtained without a facility in basic logic.
Alu Insertion Polymorphisms for the Study of Human Genomic Diversity
“The old Alu subfamilies (Sx, J, and Sg1), which comprise the vast majority (>1,000,000 copies) of the Alu elements present in the human genome, appear completely inactive as none of their members have been associated with de novo Alu inserts”
Yes, a number of Alus appear to do something. But over a million Alu’s can’t jump, don’t jump, won’t jump. Half of those just there sit untouched in intergenic space, buried in heterochromatin; the consequence of historic infections, like smallpox scars or a polio limp. They are nonfunctional; they are ex-elements. They are junk.
It is absolutely astonishing to see Pellionisz' citing abilities, next to his grasp of fact.
@ Allan Miller:
Yes, a number of Alus appear to do something.
Since we absolutely agree in this basic scientific conclusion, I do not think that there is an issue of "logic".
Fact is that absolutely nobody can claim knowledge of the unknown; exactly what percent (properly rounded or not) will be the "final" result for newly found functionality in what formerly was non-genic, "therefore Junk".
True scientists could do what makes sense: (1) continue on the new path of exploring function where - according to the old school - could not be any. (2) wanting to play a "numbers'game" do what Birney and Mattick did for fun (made a bet for a case of vintage champagne around a fictive magic number).
(3) I am stepping into the direction of advancing genome informatics how whatever percent that is found at any given time functional could regulate the genome-epigenome system (yes, use fractal geometry for reasons showing that recursion used is best characterized as fractal iteration).
I am not requiring anyone to follow my choice - though welcome all who sooner or later will. I am absolutely comfortable and happy for all doing choice 1.
As for choice 2., I don't do it, because I don't like betting (I never liked Vegas and don't even like champagne). I don't mind at all if some do that - but would not call them scientists for that entertainment alone.
So where do we (or our logic) disagree?
Over there, the ad hominem-s still rage around the "Myth of Junk DNA", but finally Ohno's "non-genic, therefore Junk DNA" nonsense is dead as a doornail.
Central Dogmatist still plays his solitary shell-game (where hides the "right" version of the Dogma to fit the occasion), but his Junk-conclusion melted into clarity: "Nobody questions the fact that lots of non-protein-coding DNA has a function."
A guessing game of percentages (by one who can't even produce properly rounded percentages) can go on ad nauseam, but who cares?
The task that really matters is to explain genome regulation by those whatever percentages of intergenic and intronic segments that most mistakenly called "Junk" - but now the many bits of function must be put in a larger (and mathematical) frame.
If the algos are not palatable to computers, solution will not be attained.
is the central dogma of molecular biology acceptable in the 21st century??
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