Sunday, February 27, 2011

Debating the Existence of Junk DNA


The sixth question for my students is ...
Do you think that most of the DNA in our genome is junk? Explain your answer.
This requires that the students take a position and defend it. That means they have to understand both sides of the argument in order to engage in truly critical thinking. It doesn't matter which side you take—I'll even accept a wait-and-see position if it's well argued.

We've seen repeatedly in the scientific literature and on the blogs that many professional scientists couldn't pass this question on an exam. Is it naive to think that undergraduates can master a topic like this?

[Dog Ass Plots] [Genome Size, Complexity, and the C-Value Paradox]

19 comments :

  1. Most of it is junk in the sense that we name it "junk DNA". But I doubt that it is junk in the sense of being useless.

    My tentative opinion is that the junk DNA is important for future evolution of the population. It's a reservoir of variation. To serve that role, it does not need to code for proteins. It only needs to be potentially transposable to a locus where it would encode.

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  2. nwrickert says,

    My tentative opinion is that the junk DNA is important for future evolution of the population. It's a reservoir of variation. To serve that role, it does not need to code for proteins. It only needs to be potentially transposable to a locus where it would encode.

    There's no question that what you say is correct. That vast reservoir of junk DNA can certainly be a source of new information in the future. Evolution is very opportunistic and it will take advantage of whatever DNA sequences are avaiable.

    Do you think that explains why humans have so much junk DNA? Does it explain why fruit flies have so much less? Does it eaplain why yeast and bacteria have almost none?

    I hope you're not saying that there's been selection for large amounts of junk DNA in order to facilitate future evolution.

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  3. "I hope you're not saying that there's been selection for large amounts of junk DNA in order to facilitate future evolution."
    I certainly would not say that. I'm not suggesting any explicit planning for the future. In any case, it is probably a mistake to talk about selection for specific traits. In most cases, it is probably selection for a package deal.

    A population has a higher probability of surviving changes in the environment, if there is greater variation within that population. So that should favor increased variation. On the other hand, with greater variation, many of the variants will be selected against, causing lower survival rates. So that would oppose increased variation. If the increased variation is in the junk DNA, however, then it is protected against that negative selection. So it allows a population to maintain a higher level of variation than would otherwise be possible.

    The problem of maintaining a high enough level of variation to survive environment change is most severe for species of low fecundity. So having a lot of variation sheltered from negative selection should be more beneficial to ape populations than it is to populations of yeast or of fruit fly.

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  4. I hope you're not saying that there's been selection for large amounts of junk DNA in order to facilitate future evolution.

    This is backwards. The selective pressure has been for metabolic efficiency in smaller, more rapidly reproducing, less multicellular organisms. Bigger slower organisms have more DNA because they can.

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  5. Bigger slower organisms have more DNA because they can.

    Like those big and slow Onions?

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  6. Like those big and slow Onions?

    You mean the multicellular, macroscopic, one generation per year Onions? Yes. Exactly like those Onions.

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  7. anonymous says,

    This is backwards. The selective pressure has been for metabolic efficiency in smaller, more rapidly reproducing, less multicellular organisms. Bigger slower organisms have more DNA because they can.

    I'm particularly fond of those big slow amoeba that have 100 times more DNA than we do.

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  8. I'm particularly fond of those big slow amoeba that have 100 times more DNA than we do.

    Yes, the exceptions to the rule are always fun, aren't they?

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  9. I'm particularly fond of those big slow amoeba that have 100 times more DNA than we do.

    What seems to matter is not the size of the organism or multicellularity but rather the size of the cells. A.proteus is huge. Onion cells are big. Yeast cells are very small. Even filamentous yeasts-like fungi (e.g., Ashbya gossypii) have very small genome.

    There is a physical limit to the amount of DNA a cell of given size can fit.

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  10. I, for one, welcome our new Amoeba overlords.

    ;-)

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  11. DK said: What seems to matter is not the size of the organism or multicellularity but rather the size of the cells.

    It seems that way to me too. Here's an attempt to quantify things.

    E Coli has about 10% junk, and its DNA is about 3% of its (dry) biomass. So junk is about 0.3% of biomass.

    The mass of DNA in a single human cell is on the order of 6e-12 grams. The number of cells in the human body is, lets say 3e13 (ignoring red blood cells). That makes .18kg DNA, nearly all junk, and a human weighs 60kg, so biomass is about 20kg, so the proportion is about 0.9%. It's a wobbly estimate, but it is the same order as E Coli.

    http://amoeba.ifmo.ru/species/amoebidae/aprot.htm says Amoeba proteus averages about 220-740 μm in length while moving, and the pictures make it look pretty stringy in shape. Oh dear, this is going to be even more wobbly. If we say a .2mm cube, that would weigh 8e-6 grams and I'll guess its 75% water, so 2e-6g biomass. Its 100x as much DNA as human, and I guess mostly junk, so 6e-10g. That's a mere 0.03% junk.

    In general, what kind of organisms have unusually low or high junk/biomass ratio?

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  12. What I call “The TNT of Genomics” blew the good old Gene-Junk myth into fractals.

    The Treasure / Not known / Trash functional tri-partition (TNT) demolished the “Old School”, hopefully in a graceful manner.

    The speech that provides emphasis was by The Science Advisor to the U.S. President, Eric Lander on YouTube at the NIH Decade Celebration on February 11, 2011 (see detailed analysis at the HoloGenomics.com column “news”).

    By TNT, small parts of Junk DNA have been truly “Trashed” (their pathological mess revealed, e.g. excessive intronic triplet runs have been proven to be the cause of scores of diseases). An ever-increasing “Treasure” part, that is already five times of the size of protein-coding sequences as Lander points out, is growing explosively with identified and critical role of genome regulation. The gap between the Treasure and Trash parts of the genome leaves, of course, a rapidly shrinking “Not (yet) known” territory.

    A few sophisticated mathematical (algorithmic) approaches, like FractoGene (2002), make sense of infamously repetitive bits and pieces, of what is treated, for lack of a better word a “Complex System”. It was pointed out in Cold Spring Harbor Labs (2009) that “complexity is in the eye of the bewildered”.

    In view of the disruptive paradigm-shift by TNT of Genomics, neither the title of this blog, nor the question to students make much any sense, anymore.

    “Debating the Existence of Junk DNA” assumes that Junk may or may not exist. A universally accepted new definition of what a “gene” might be, certainly does not exist, perhaps it would have been a more interesting question if “Gene” or “FractoGene” makes more sense to students. On the other hand we know with scientific certainty that certain structral variations may cause people get seriously ill, or worse. Thrash, getting into our systems kills many (too many) millions.

    The question to students is equally missing the point “Do you think that most of the DNA in our genome is junk? Explain the answer”

    Students might hesitate how to intelligently answer a question that is irrelevant – before a comprehensive understanding of genome function other than the obsolete gene/junk myth is applied. The true scientific question is not the relative amount of TNT components (that is very dinamically changing even in this website, anyway).

    The urgent science question, and task for the best and brightest students is, in order to save hundreds of millions of people, from dying, the algorithm how genome regulation works. As Eric Lander showed in his talk, there is evidence that the structure of DNA is fractal. He also said (answering the single allowed question) “We are going to need tremendous input from informatics folks, from computer scientists to think about this … but this is in the spirit of the Genome Project that has always been to reaching out to different fields and Lord knows at this point we are going to need help from a lot of fields…”

    Once someone from the field of genome informatics put forward The Principle of Recursive Genome Function, the fractal iterative recursion suddenly explains tons of “genomic mysteries”, e.g. the “exceptions” quoted above. Anyone with a degree in abstract sciences can make a recursion by an almost trivial parametric change to be extremely fast converging (needing small amounts of DNA information to sustain recursions) – or e.g. with primitive ill-tuned recursions the convergence may be slow as an amoeba, needing tons of DNA information to keep recursions running, while not getting that much ahead).

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  13. @ Pellionisz

    Please explain the results of the paper below, based on your posistion.

    http://www.nature.com/nature/journal/v431/n7011/abs/nature03022.html

    Abstract:
    The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined1. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts2, 3, 4 can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially 'disposable DNA' in the genomes of mammals.

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  14. The half a Century of mistaken axioms has run it’s full course. I am glad for Genomics that we are over the stages of denial, rage and depression and the field at large is ready to embrace the most viable postmodern solution(s). The inconclusive explanation to the ill-posed question of removal of 3% full text) I resolved 7 years ago here. Nobrega's caveat: "It is possible, even likely, that the animals carrying the megabase-long genomic deletions do harbour abnormalities undetected in our assays". More profound criticism was by Dave Haussler that "Survival in the laboratory for a generation or two is not the same as successful competition in the wild for millions of years".

    I stress that the issue now is not the size of (TNT parts of) the Genome – but one can be beaten in that side-game, too (1989-2006):

    The iterative fractal recursion generating a P-cell (see the concept Pellionisz, 1989, Fig. 5. FractoGene shows (see Fig. 3. copy from Pellionisz, 2002, and Fig. 4. in Simons and Pellionisz 2006), that Mother Nature can generate a P-cell using very little “non-coding DNA”, since in the Fugu 0.037 Bn can do it, while a much more elaborate P-cell is generated in mice with 2.6 Bn bases, about the same as in the guinea pig P-cell (whose fractal model was produced in 1989). In 2006, the genome size of the guinea pig was not known, but the fractal prediction that it would be very comparable with the mice has since been proven. What if a guinea pig would have to do with Purkinje neurons of a mice (with hardly distinguishable amount of non-coding DNA)? The answer is visibly “unnoticeable”.

    The more timely issue was raised just days ago in this news that stressed “Revolutions in science come in waves … Modern biology is all about automated machines churning out huge amounts of data, ... to be managed, stored, analyzed and visualized … None of these procedures amount to rocket science, but if you don’t do it, there is actually no point to conducting the experiment in the first place.”

    I add that in postmodern Genome Informatics establishing sound axioms (Pellionisz, 2008 peer reviewed paper and YouTube) is the cardinal issue, before data automation, management, storage, analysis & visualization. This requirement to be critical, e.g. of Crick's "Central Dogma", was emphasized by Crick himself (1970) "If it were shown that information could flow from proteins to nucleic acids then such a finding would shake the whole intellectual basis of molecular biology". Francis Collins also reminded us upon releasing ENCODE (2007) that "the scientific community will have to re-think long-held beliefs". Craig Venter also warned, that (2010) "our understanding of genome regulation is frighteningly unsophisticated". Now (2011) Eric Lander tells NIH that the basic assumptions were all wrong, and that the structure of DNA is fractal.

    So I am glad that after 2009 September or 2009 October(Mr. President, the genome is fractal!) – moreover in 2011 February it is appreciated that the intellectual paradigm-shifts have shaken up the intellectual basis since 1989.

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  15. Pellionisz @ Monday, March 07, 2011 6:09:00 PM

    So to paraphrase, "I can't explain it. Now listen to me rant and obfuscate". Is this correct?

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  16. Dear The other Jim, brain surgeons (or drugs) can remove 3% or more of the cortex without apparent result except that the person can still perform bodily functions, but will not be able to meaningfully engage in intellectual debate, or understand, that fractal recursive iteration is mathematically infinite, yet its material manifestation is bounded by the finite due to impositions. The first sign of altered intelligence is often a damage to someone's identity, typically masked by anonymity chosen to hide their embarrassment over their limited capacity. Most blogs have abandoned accommodating such noise, elsewhere they shall be ignored.

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  17. brain surgeons (or drugs) can remove 3% or more of the cortex...

    A false analogy. Irrelevant to my question.

    The first sign of altered intelligence is often a damage to someone's identity, typically masked by anonymity chosen to hide their embarrassment over their limited capacity. Most blogs have abandoned accommodating such noise, elsewhere they shall be ignored.

    Argumentum ad hominem. Again irrelevant to the question.

    That leaves you with just
    .., that fractal recursive iteration is mathematically infinite, yet its material manifestation is bounded by the finite due to impositions.

    Which, as far as I can tell is simply a "Proof by verbosity". If I am incorrect, please supply a translation.

    Otherwise, it is clear that your theory cannot explain this observation (unless you wish to pull the "assay not sensitive enough" / Russel's teapot argument).

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  18. Those with no idea what fractal iterative recursion might be are kindly advised to study the literature I provided by links to the free full texts of peer-reviewed science publications. Anyone with more superior explanation is encouraged to go on public record with their competing mathematical explanation.

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  19. Your catch phrase still still does not answer my question.

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