Can mutations produce mutation repair systems?


#41

What you have to be wary of is the “affirming the consequent” fallacy.

If A, then B
B
Therefore A

There is DNA that is transcribed into functional non-coding RNA. However, just because DNA is transcribed into RNA does not mean that the DNA codes for a functional non-coding RNA molecule. To use a bad analogy, there are air filters that pull in air and bind dust particles on their filter. If I smash a TV into a million little pieces and pile them on the floor, those pieces will bind a few dust particles as they float by. Therefore, since the busted up TV binds dust particles just like the functional air filter, then the busted up TV must be functional as well. This is the (bad) logic that ENCODE used to justify RNA transcription as an indicator of function. For some “functional” RNA molecules in the ENCODE study they were found at less than 1 copy per cell, and yet they still called them functional. To make things worse, ENCODE also used several cancer cells lines that are known for leaky RNA transcriptase activity.

As Larry Moran over at the Sandwalk blog puts it, non-function is the null hypothesis. You need evidence for function before you can say that an RNA molecule or even a translated protein has function. One of the most well recognized pieces of evidence is sequence conservation, and only a small fraction (~10% of the human genome) shows evidence of conservation. Can DNA still have function without showing evidence of sequence conservation? Yes, that is possible, and I wouldn’t be shocked if 1% or even 5% of human genome was functional but showed no signs of conserved sequence (although 5% is really pushing it). Is it possible that 70% of the human genome that shows no evidence of sequence conservation somehow still has function? I think that is fantasy, and yet that is what ENCODE suggested when they said 80% of the human genome has function.


#42

Well, the argument my forementioned colleagues used to justify that was the recent studies with single cell transcriptomics like these ones:

But then again, it is not my area, so I can’t really tell if they are just insisting on fringe ideas, which happens sometimes in science even in respectable groups. It does seem however that some amount of non-coding RNAs are required, though they are far less than the 70-80% suggested by ENCODE.


#43

But yeah, if I had to give my non-specialist guess I would say that probably some of the non-coding RNA is actually important but the remaining 70% of the genome or so is likely “junk”.


#44

This is where affirming the consequent is easy to commit.

Molecule A has function, and it is an lncRNA.
Molecule B is an lncRNA.
Therefore, Molecule B has function.

High expression in the absence of sequence conservation is weak evidence for function, but it is still enough evidence to separate candidates from non-candidates. They would still need to do follow up work with any promising lncRNAs they find, and find out what effect they actually have in the cell. After that, they would need to show that this effect makes an impact on fitness.

As Dobzhansky said, nothing in biology makes sense except in the light of evolution, and function is one of those things. If you get rid of something and it doesn’t make an impact on fitness, then it was disposable DNA. Do these RNA molecules make an impact on fitness? That’s the big question.


#45

I see your point. Indeed, poor sequence conservation is a huge case against functionality of junk DNA. It makes me wonder how evolutionary pressure allowed that much junk DNA to accumulate in the first place, though. Pufferfish seems to be doing just fine with its low content of junk DNA, did they just get “lucky” to develop very efficient systems to get rid of it better than we and other species do?


#46

There aren’t strong enough selective pressures for removing it. Any process that removes DNA from a genome is also going to remove functional DNA, so there can be a balancing act between removal of DNA and deleterious mutations.

One curious case that has always intrigued me is the bladdwort, which is a carnivorous plant found in nutrient poor environments. Its genome is just 82 million bases, yet it is thought to have about the same gene content as the human genome. If memory serves, 80-90% of its genome is thought to be functional. Given that it lives in a nitrogen and phosphorous poor environment it is easy to think that this small genome size was driven by the need to conserve those resources, but faulty adaptionist conclusions are easy to jump to. Nonetheless, we do have example of nature doing the experiment for us in removing most of the suspected junk DNA from a genome, and what you get is a fully functioning and healthy species.


#47

Yeah, but 80-90% useless DNA just seems to much of a waste of energy and replication time…I’d be fine with 10 or even 20% completely useless DNA, but 90% just seems like overkill. Not impossible, though, as you said not everything that passes by through evolution is necessarily adaptive. Anyway, thanks for the insights, I think I’m going to stop here before I go full off topic, haha.


(Mervin Bitikofer) #48

I’ll ask advance forgiveness for what is probably a stupid question; it most certainly is from a “lay-lurker” on genetics questions in any case. You wrote:

This makes sense, (to the extent that I vaguely understand the concepts). Here is my question, though. Is it possible that all the non-coding DNA fills some sort of generic “filler” function just by its very existence? I.e. While any one bit of it might be easily shown to be non-essential to an organism’s fitness, might there still be an indirect and yet just-as-important function it fulfills just by being there? I don’t just mean in an incidental way (like the smashed TV happening to bond with some airborne particulates – I appreciate and agree with your examples that this does not represent true function). No; what I mean is more like this: If we were to ask whether rain drops (or the individual water molecules) were functional to our ecosystem, and we could follow thousands of these molecules from their rain cloud drop, we might discover that the majority of them just end up evaporating again, or run off into rivers without ever becoming used in the roots of a plant. So we might conclude (erroneously) that most fresh water in the world is nonfunctional. And yet, we know that it actually is functional because without the overabundance of water, the molecules that do reach and supply needy bio-organisms probably never would have. So a lot of “filler” water is needed just to enable the small amounts of directly used water to reach the places it needs. Removing single rain drops has no measurable effect on the environment.

So you can remove certain DNA sequences and don’t see any effect … But what if all the noncoding DNA was removed, leaving a lean-mean function-dense DNA molecule? Might we not find that organisms need a large (and mostly unused at any given evolutionary point of history) DNA scratch pad space on which to play around? I know this probably isn’t what geneticists mean when they differentiate between coding and noncoding, but is there anything to my comparison?


(Jon) #49
  1. You didn’t provide any “empirical evidence”.

  2. The “peer-reviewed article” was one you co-authored. It was published in a journal with an absolutely insignificant impact factor of 0.64. The publisher of the journal is known for lack of academic rigor and unethical practices. If your paper had any credibility you would have no difficulty getting it published in a high impact journal by a reputable publisher.

  3. The “letter of the Class for Chemistry of the Royal Swedish Academy of Sciences” says absolutely nothing to support your claims. It specifically contradicts you, by saying that genetic mutations occur, and they are essential for evolution to take place.

  4. You have demonstrated once again that you have not followed the scientific method; you have been unable to provide any evidence of hypotheses, experiments, and evidence based conclusions.

This proves you do not understand mutations and their effects. Do you agree that “mutagenic chemicals and radiation can also have a healing effect”? Because that’s a statement made in the “letter of the Class for Chemistry of the Royal Swedish Academy of Sciences” which you appealed to.

Your pseudo-scientific gibberish won’t get any support here. People are too well informed about science. You’re better off taking it somewhere like AiG.


(Andrew M. Wolfe) #50

Your link doesn’t critique Bentham’s peer-review process, but Wikipedia does:

Bentham Open journals claim to employ peer review; however, the fact that a fake paper generated with SCIgen was accepted for publication, has cast doubt on this.

Other interested Forum visitors can read more here: https://en.wikipedia.org/wiki/Bentham_Science_Publishers.

The good news is, William’s article does have measured impact! That is to say, it has precisely one citation, according to Google: this response article by Gerdien de Jong… who is perhaps incensed that someone sharing his name (minus a space) has published something he feels is so obviously spurious. His abstract:

DeJong & Degens (2011) conclude from the properties of digital codes that ‘nucleotide codes’ should have similar mutation protection. I argue that digital codes and ‘nucleotide codes’ are not sufficiently similar to draw conclusions about mutation protection and evolution. A ‘mutation protection paradox’ does therefore not exist in biology.


(Jon) #51

Actually it does, and gives two examples, one of which is the SIGen article.

In April 2009, the Open Chemical Physics Journal published an article advocating 9/11 conspiracy theories without anyone bothering to inform the journal’s editor, who promptly resigned.[5]

This aroused the interest of the curious, and Bentham was busted in 2009 accepting a paper for the Open Information Science Journal consisting of random sentences computer-generated with SCIgen, whose imaginary authors both worked at the Center for Research in Applied Phrenology (CRAP).[6][7] The editor of said journal also quit when he found out what the publisher had done.[8] Bentham’s director of publication claimed they merely sent a fake acceptance to flush out the hoaxer,[4] but no-one believes him.

I really enjoyed this find of yours.

DeJong & Degens (2011) conclude from the properties of digital codes that ‘nucleotide codes’ should have similar mutation protection. I argue that digital codes and ‘nucleotide codes’ are not sufficiently similar to draw conclusions about mutation protection and evolution. A ‘mutation protection paradox’ does therefore not exist in biology.

So that article has one single citation after 7 years (!), and it’s from someone debunking it.


(Andrew M. Wolfe) #52

My bad. Guess I didn’t read your link very carefully! But yes… exactly. Rather shows the opposite of what he was intending to show…


(Stephen Matheson) #53

These are great questions. If I read you right, you are pointing to one potential “use” for “junk DNA,” which is to provide fodder for further adaptation. If so, then while it might be valuable to an individual organism, on the spot, to have a lot less repetitive DNA to carry around, it would be problematic over long time-spans due to the loss of evolutionary opportunity. And in fact, studies of “proto-genes” in current genomes are a new thing. We know of genes that clearly used to be “junk,” so therefore we can surmise that those genes (and any associated adaptations) wouldn’t exist without “junk.”

At first glance, we might therefore conclude that junk DNA is not only valuable but utterly necessary for evolution, at least in animals and plants with genomes composed largely of repetitive elements. I think the main challenge to that reasoning is that we don’t really know the evolutionary cost-benefit matrix. We know that there is a cost to copying and maintaining a genome. We know that there are risks inherent in maintaining a complex genome, and especially in maintaining a genome with a lot of repetitive elements. On the other hand, we know of various benefits and “functions” of what looks like junk DNA. (Two examples we might discuss further: genome size is related to cell size, and junk-like introns can be used to control speed of gene expression.) We really don’t know how much “junk” would suffice to provide evolutionary opportunity, and we may reasonably wonder whether it is much, much less than the amount we are saddled with.


(Mervin Bitikofer) #54

Thanks for your clarification – and affirmation that I’m not totally bonkers. Indeed you stated my intent better than I had managed to with this observation:

…which captures exactly where I was trying to go (or to try restating again for myself): Perhaps there is a long-term evolutionary benefit to all the stuff being carried even when it has no immediate benefit to the individual organism that carries it.

Indeed. The first article you linked brought more of that quandary into focus for me.

It seems to offend our engineering sensibilities (for some Christians anyway) that a designer should be so profligately wasteful. They want 100% or 0%; but it also seems to me that we (Christians) ignore what I think I’ve heard referred to as a “principle of plenitude” which probably is a time-honored concept from well before modern science. God regularly delights in overabundance (in some things, and in some places, for some people – with all due respect to those who rightly may wonder where all this abundance is in wealth or food resources). But acknowledging such hardship, I’m still focusing more on the scientific observations we make: that 99.9…% of our sunlight shines off “uselessly” into the cold of space. Or that 99.? % of water shuffles about in the water cycle without directly servicing a thirsty organism in any given season. I don’t doubt these examples could be and have been multiplied.

It seems that when engineers among us get our creationist (or anti-creationist) dander up about “efficiency”, God just laughs. Our solar system could have been “exquisitely designed” with some mechanism to contain all our sun’s energy and release only a tight laser beam of it to illumine the earth (and perhaps a few more tight beams so that the other planets would be lit up to grace our night skies – it is “all about us”, after all, right?) And in fictitious “beam universe” the engineer swells up with pride and pleasure at the vastly increased efficiency of our star’s energy use. And yet we now see all the potential problems too. Should the earth’s orbit vary by just a bit, we might drift away from that carefully tracking laser, always needing to stay on that knife edge path – iceball death threatening from every side. But lo and behold, our fictitious “problem” gets its lethal blow from the reality of our sun casting its plentiful energy in all directions. Our poverty-enforced efficiencies that oblige human engineers to minimize waste (in the context of economies and systems we have set up for ourselves) do not exist for God. I indulge myself in the speculative possibility that DNA may also follow a similar principle in a wider context of evolutionary time scales. How unfortunate that so many of us Christians have shut down the consideration that would open up this possible dimension of God’s activity to our full appreciation. At least that’s my religiously-motivated take on it.

But I will cease from this digression on an otherwise scientific thread. Carry on that we all may learn more!


(William DeJong) #55

This post was flagged by the community and is temporarily hidden.


#56

Enzymes couple thermodinamically favorable reactions in order to compensate to the unfavorable ones, one example I can give is the plasma membrane Ca2+ ATPases, they pump Ca2+ from a very low, negative-inside membrane to a external media containing huge amounts of Ca2+, which at first glance seems completely against the laws of thermodynamics, however, they hydrolyze one molecule of ATP to ADP in the process, which ultimately makes the global reaction favorable. There is absolutely no fantasy on that.


(William DeJong) #59

Your are right! Miller built a (simple) amino acid factory, but he spread the fake news that natural processes can produce and every growing amount of amino acids. See further, conclusion 6 of my post on 7 April.


(William DeJong) #61

Your are fighting the progress of science. Any program or recipe (for instance for the production of an apple pie or a human being) consists of a relatively small part that describes WHAT will be processed, and another part that describes HOW and WHEN.


(William DeJong) #62

Dear Boltzmann Brain,
Indeed, enzymes are interesting molecules. But only in the fantasy world of Naturalists, Darwinists and Alchemists, enzymes are capable of organizing molecules into ever growing structures with an ever growing energy content. In the real world this is impossible, because if enzymes would possess this magical property, energy would become available for free (‘proof by contradiction’). See further conclusion 6 and 7 of my post on 7 April.


(William DeJong) #63
  1. The peer-reviewed article of DeJong and Degens (2011) mentions the basic scientific facts on how the DNA changes. See further conclusions 1 and 2 of my post on 7 April.
  2. A colleague has opposed to the article by claiming that there is no mutation protection paradox, but did not provide any argument.