Thursday, November 21, 2013

Claudiu Bandea Shows Why Attacking Dan Graur Is a Very Bad Idea

Claudiu Bandea is a frequent commenter on this blog. Whenever the subject of junk DNA comes up he reminds us that he had a theory over twenty years ago. Now he has published(?) an advertisement at: On the concept of biological function, junk DNA and the gospels of ENCODE and Graur et al.. Here's the abstract ...
In a recent article entitled “On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE”, Graur et al. dismantle ENCODE’s evidence and conclusion that 80% of the human genome is functional. However, the article by Graur et al. contains assumptions and statements that are questionable. Primarily, the authors limit their evaluation of DNA’s biological functions to informational roles, sidestepping putative non-informational functions. Here, I bring forward an old hypothesis on the evolution of genome size and on the role of so called ‘junk DNA’ (jDNA), which might explain C-value enigma. According to this hypothesis, the jDNA functions as a defense mechanism against insertion mutagenesis by endogenous and exogenous inserting elements such as retroviruses, thereby protecting informational DNA sequences from inactivation or alteration of their expression. Notably, this model couples the mechanisms and the selective forces responsible for the origin of jDNA with its putative protective biological function, which represents a classic case of ‘fighting fire with fire.’ One of the key tenets of this theory is that in humans and many other species, jDNAs serves as a protective mechanism against insertional oncogenic transformation. As an adaptive defense mechanism, the amount of protective DNA varies from one species to another based on the rate of its origin, insertional mutagenesis activity, and evolutionary constraints on genome size.
It's not a good idea to attack someone who; (a) is an expert in the field, (b) is intelligent and outspoken, and (c) has a blog. But that never stopped Claudiu Bandea before so why should it now?

Here's part of how Dan Graur responds at: A Pre-Refuted Hypothesis on the Subject of “Junk DNA”. There's more, read it all.
The first problem with this hypothesis is that big eukaryotic genomes consist mostly of very few active transposable elements and numerous dead transposable elements. So, big genomes seem to need little protection. Moreover, a positive correlation exists between genome size and number of transposable elements. In 2002, Margaret Kidwell published a paper entitled “Transposable elements and the evolution of genome size in eukaryotes.” In it, she showed that an approximately linear relationship exists between total transposable element DNA and genome size. Copy numbers per family of transposable elements were found to be low and globally constrained in small genomes, but to vary widely in large genomes. Thus, the major characteristic of large genomes is the absence of selective constraint on transposable element copy number.

Given that the vast majority of transposable elements are dead, the most parsimonious explanation is that the continuous accumulation of dead transposable elements is the reason for genomes becoming large. Let me spell it out: the “large” part in “large genomes” is made of transposable elements. Genome do not become large first and then protect genetic information by becoming sinks of transposable elements.

The other problem with the protection-from-mutation hypothesis is that it assumes selection on mutation to be effective. Selection on mutation is referred to in population genetics as second-order selection. The reason is that this type of selection is anticipatory. It protects against a possibility, not an actuality. Second-order selection on mutation (mutability) requires huge effective population sizes, so huge in fact that they are only found in a few bacteria and viruses. Unfortunately for the protection-from-mutation hypothesis, genome size is known to be inversely correlated with effective population size. In other words, huge genomes are found in species that have very small effective population sizes. So small, in fact, that even regular selection (first-order selection) is not very effective.

Thomas Huxley was proven right again: "The great tragedy of Science is the slaying of a beautiful hypothesis by an ugly fact." Several ugly facts in this case.
I can't count the number of people who have tried to explain to Claudiu Bandea that his idea is ridiculous. Hopefully, this last embarrassment will silence him.

Naturally, the Intelligent Design Creationists are all over it [Another response to Darwin’s followers’ attack on the “not-much-junk-DNA” ENCODE findings].


2 comments :

  1. OMG!!!
    Dan Gravel:

    "The first problem with this hypothesis is that big eukaryotic genomes consist mostly of very few active transposable elements and numerous dead transposable elements"

    Is that a fact? Or is it another of Dan's assertions based on his believe....?

    Gravel:

    "So, big genomes seem to need little protection. Moreover, a positive correlation exists between genome size and number of transposable elements."

    That may very well be true but the question is: Is there kind of some consistency in evolutionary theory regarding this assertion? Can I find more than one example that disproves this assumption and say; Well evolution must have taken some time off when this happened...? Anybody wanna bet? Dingene?

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  2. How would you respond or react to a post like this? Apparently, with silence!

    Until now, the only exception was Quest, who could not restrain himself and exclaimed “OMG!!!”

    Indeed, OMG!!! Unlike Larry Moran’s empty and arrogant take on my theory, a take that circumvented scientific arguments, in his post Dan Graur expressed his critique by presenting scientific evidence, which he thought go against my theory. On the rhetorical side of the story, Dan encouraged me to bring the theory forward so that other scientists can evaluate it, and he tweeted among other things: “Claudiu Bandea is a very thoughtful scientist. But on this occasion he is wrong”, which is reasonable. So, obviously, he did not consider my paper an “attack”, as portrayed by Larry.

    For those interested in the scientific side of the story, here is an excerpt from my response to Dan’s arguments:

    “As guardian-in-chief of junk DNA (jDNA), Dan Graur has been very sharp (to sharp, some people say) in his shattering critique of ENCODE’s conclusion that at least 80% of the human genome is functional. However, in his response above ("A Pre-Refuted Hypothesis on the Subject of "Junk DNA") to my paper he seems rather distracted.

    To begin with, Dan refers to my hypothesis as a nucleotypic theory, which it is not. I would recommend he reads some of the many publications on the nucleotypic theory, such as those by Ryan Gregory (e.g. 1, 2); also, he might want to read my paper again, as I specifically addressed and questioned the nucleotypic theory; see also my recent PubMed Commons note (3) on Ford Doolittle’s article "Is junk DNA bunk? A critique of ENCODE" (4) in which I address the nucleotypic theory.

    Next in his response, Dan expresses his love for my hypothesis, as he calls it "a beautiful hypothesis", only to realize (I presume under the pressure of his day-job as guardian of jDNA) that the ‘beaut’ was born "pre-refuted."

    Then, Dan outlines a series of evidence/arguments that suppose to "pre-refute" the hypothesis but, surprisingly, are consistent with, or support the hypothesis:

    (i) "big eukaryotic genomes consist mostly of very few active transposable elements and numerous dead transposable elements";

    (ii) "a positive correlation exists between genome size and number of transposable elements";

    (iii) "an approximately linear relationship exists between total transposable element DNA and genome size";

    (iv) "Copy numbers per family of transposable elements were found to be low and globally constrained in small genomes, but to vary widely in large genomes";

    (v) "the major characteristic of large genomes is the absence of selective constraint on transposable element copy number";

    (vi) "Given that the vast majority of transposable elements are dead, the most parsimonious explanation is that the continuous accumulation of dead transposable elements is the reason for genomes becoming large";

    (vii) "Let me spell it out: the "large" part in "large genomes" is made of transposable elements";

    (viii) "huge genomes are found in species that have very small effective population sizes", which, without a protective mechanism against insertion mutagenesis, would have little chance to survive evolutionarily.

    References
    (1) Gregory TR, Hebert PD. 1999. The modulation of DNA content: proximate causes and ultimate consequences. Genome Res. 9(4):317-24.
    (2) Gregory TR. 2004. Insertion-deletion biases and the evolution of genome size. Gene, 324:15-34.
    (3) Bandea CI. 2013. Junk DNA is bunk, but not as suggested by ENCODE or Doolittle. PubMed Commons (http://www.ncbi.nlm.nih.gov/pubmed/23479647#cm23479647_1429)
    (4) Doolittle WF. 2013. Is junk DNA bunk? A critique of ENCODE. Proc Natl Acad Sci USA., 110:5294-300.


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