Last week, there were two HuffPost blogs on the release of the ENCODE (Encyclopedia of DNA Elements) project data: mine and one by colleague Michael White. We took opposing positions on the question of whether the ENCODE results are compatible with the "junk DNA" explanation for so much mobile repetitive DNA in our genomes. Such disagreements are normal in evaluating the importance of scientific evidence.
By demonstrating the connection between replication and transposition of DNA transposons in 1979 (Shapiro 1979), I was in part responsible for the idea, supported by White, that a sufficient explanation for the presence of mobile repeats is their ability to replicate and amplify in the genome. Two 1980 Nature papers expressed this hypothesis (Doolittle and Sapienza 1980; Orgel and Crick 1980).
When I corrected a small misstatement in White's blog about one of the 1980 Nature papers, it elicited the following comment from diogeneslamp0:
White: "junk DNA...was not based on what scientists didn't know, but rather on what they did know"
Shapiro: "This is not exactly correct."It is exactly correct. The idea that human DNA was largely limited in its functionality was based on applying simple principles of population genetics to what we knew about the genome. If every baby has 50-150 new mutations, it's impossible for all 50-150 mutations to be deleterious; that would cause the extinction of man.
Diogenes' comment is typical of those from many defenders of the "junk DNA" idea and reflects the kind of absolute thinking that has no place in real science. Nothing is ever "exactly correct." All measurements have uncertainties, and all explanations have a limited life span.
The scientific enterprise is inherently tentative. We cannot know how our understanding of phenomena will change with unexpected new results. Contrary to what White argued, the interpretation of the ENCODE data as invalidating the "junk DNA" hypothesis was not a "media failure." It was the explicit conclusion of the ENCODE project scientists published in Nature:
One of the more remarkable findings described in the consortium's "entrée" paper is that 80% of the genome contains elements linked to biochemical functions, dispatching the widely held view that the human genome is mostly "junk DNA."
My point in writing this rethinking of the ENCODE/Junk DNA debate is not to re-argue the substantive merits. Instead, my goal is to illustrate how unscientific are expressions of certainty and permanence in arguments about interpretations of natural phenomena, like the static views expressed by Diogenes.
I am fortunate to be able to do this examination of scientific reasoning from a perspective on molecular genetics that dates back to the early 1960s, before we knew about repetitive DNA. At that time, we were just beginning to assimilate the operon model (Jacob 1961) and learn about the regulation of genome expression, replication, transmission and repair. Thinking was still focused on the "one gene-one enzyme" (Beadle 1948) view of heredity. The idea of Barbara McClintock that mobile segments could serve as "controlling elements" (McClintock 1952) to regulate genome function was far outside accepted molecular biology discourse.
The (re)discovery of mobile and repetitive DNA in the late 1960s by the molecular work of Britten and Kohne (Britten 1968) and the genetic analysis of scientists working on viruses and transposable elements in bacteria, Drosophila and other experimental organisms (Bukhari 1977) came as rude shock to the gene-centered thinking of the times. Further shocks came from discoveries about exons and introns (Chambon 1981), distant enhancer elements (Tjian 1995), and epigenetic control by chromatin formatting (Holliday 1989).
The ENCODE scientists have learned that it is wise to avoid interpreting the data from a fixed view of genome organization. That is why they speak of "DNA Elements" rather than genes or any other artificial categories. They tend to restrict themselves wisely to operationally defined features, such as transcription start sites (TSSs) and splice sites at exon-intron boundaries.
Diogenes and like-minded people argue that we knew enough in the 1970s to understand the basic principles of genome organization. They do not accept that the flood of new information from genome sequencing and the kind of methodologies exemplified by the ENCODE project will fundamentally alter our genetic concepts. While they are certainly entitled to these opinions, I think we have to recognize that they are nothing more than that -- simply opinions that fly in the face of scientific history.
There are really no fixed notions in science (Kuhn 1962). Gravity is often cited as a case of something definite. While our experience of the force of gravity is continual, our explanations of how it works have changed fundamentally over time. Wendell Read has pointed out in several comments on my blogs that Newton had to invoke an ad hoc "action at a distance," while Einstein accounted for gravity as a curvature of four-dimensional space-time. Meanwhile, physicists are busy working on a quantum theory of gravity.
As I like to repeat, if Newton could not get it right, what hope is there for the rest of us? Vannevar Bush wrote that science is an "endless frontier." We never get final answers. But then, we never run out of fascinating questions to ask.
References:
Beadle, G. W. (1948). "The genes of men and molds." Sci Am 179(3): 30-39. http://www.ncbi.nlm.nih.gov/pubmed/18884635.
Britten, R., Kohne, DE (1968). "Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms." Science 161: 529-540. http://www.ncbi.nlm.nih.gov/pubmed/4874239.
Bukhari, A. I., J.A. Shapiro, and S. L. Adhya (Eds.) (1977). DNA insertion elements, plasmids and episomes Cold Spring Harbor, New York, Cold Spring Harbor Press.
Chambon, P. (1981). "Split genes." Sci Am 244(5): 60-71. http://www.ncbi.nlm.nih.gov/pubmed/6262906.
Doolittle, W. F. and C. Sapienza (1980). "Selfish genes, the phenotype paradigm and genome evolution." Nature 284(5757): 601-603. http://www.ncbi.nlm.nih.gov/pubmed/6245369.
Holliday, R. (1989). "A Different Kind of Inheritance." Scientific American 260(6): 60-73. http://www.ncbi.nlm.nih.gov/pubmed/2543066.
Jacob, F., Monod, J (1961). "Genetic regulatory mechanisms in the synthesis of proteins." J Mol Biol 3: 318- 356. http://www.ncbi.nlm.nih.gov/pubmed/13718526.
Kuhn, T. S. (1962). The Structure of Scientific Revolutions Chicago, Univ. of Chicago Press.
McClintock, B. (1952). "Controlling elements and the gene." Cold Spring Harb Symp Quant Biol 21: 197-216. http://www.ncbi.nlm.nih.gov/pubmed/13433592.
Orgel, L. E. and F. H. Crick (1980). "Selfish DNA: the ultimate parasite." Nature 284(5757): 604-607. http://www.ncbi.nlm.nih.gov/pubmed/7366731.
Shapiro, J. A. (1979). "Molecular model for the transposition and replication of bacteriophage Mu and other transposable elements." Proc Natl Acad Sci U S A 76(4): 1933-1937. http://www.ncbi.nlm.nih.gov/pubmed/287033.
Tjian, R. (1995). "Molecular Machines that Control Genes." Scientific American 272(2): 54-61. http://www.ncbi.nlm.nih.gov/pubmed/ 7817187.
Think of all those years wasted when we could have been researching many of the clues that she discovered concerning function instead of what Stewart Newman calls hand waiving arguments or writing people off who challenge these axioms and dogmas.
Actually, McClintock stopped publishing in regular journals after her 1953 Genetics paper (on how to isolate controlling element mutations at any locus) was widely ignored. Nonetheless, she continued to published in the Annual Reports to the Carnegie Institute of Washington (http://library.cshl.edu/personal-collections/barbara-mcclintock/bibliography-mcclintock) and in symposia papers. Much of this material is available in her collected papers on transposable elements (McClintock, B. Discovery And Characterization of Transposable Elements: The Collected Papers of Barbara McClintock, Garland, New York, 1987).
Her Carnegie Institute reports contained many findings she made through the 1970s. She discovered a wide variety of phenomena involving mobile elements that were later rediscovered and characterized at the molecular level by others (Federoff, Starlinger, Saedler, Jorgensen, Chandler, etc.). Her 1956 Brookhaven Symposium paper (McClintock, B. Intranuclear systems controlling gene action and mutation. Brookhaven Symp Biol, 58-74 (1956). http://www.ncbi.nlm.nih.gov/pubmed/13293421) is a classic and summarizes a number of her findings on Ac/Ds and Spm.
I highly recommend to readers to buy the 1987 collection of her paper and read them with online help with the details of maize genetics. There were no farther-seeing biologists in the 20th Century than Barbara McClintock.
McClintock's studies and observations of mutation in kernels of maize (corn), led to her discovery of transposable genetic elements. Although the scientific community largely ignored her concepts, advances in molecular and microbial genetics ultimately proved her findings correct. She is now credited as the discoverer of transposable—or “jumping”—genes, a discovery which is at the very root of much of today's research in genetic engineering.
Thanks for bigning all this material on McClintock to everyone's attention.
If you look at my two blogs on McClintock (http://www.huffingtonpost.com/james-a-shapiro/barbara-mcclintock-x-rays_b_1322879.html and http://www.huffingtonpost.com/james-a-shapiro/barbara-mcclintock_b_1223618.html?ref=science) you will see that she was concerned with far more than just mobile DNA.
Barbara McClintock: Pioneering Geneticist (Unlocking the Secrets of Science) [Library Binding]
Kathleen Tracy (Author)
From all her experiments with maize (Indian corn), Barbara discovered that there were movable elements inside each gene, which she called "transposable elements." Because her revolutionary ideas challenged a cemented belief among mainstream geneticists that genes were fixed in place, her research was rejected. She was deeply stunned and bitterly disappointed at the close-mindedness of the scientific community.
It seems that like the the gene itself, the term junk DNA means different things to different people including many scholars and scientist. The term is to interchangeable and has no definable goal post. When speaking of parts of the genome we still do not yet fully understand, the term junk DNA should be replaced with NKF/'no known function'.
Even Wikipedia has stated. "its connotations may have slowed research into the biological functions of noncoding DNA" This is a point also echoed by many, including John Mattick who has also come under fire for challenging the status quo view. and I'm sure you have had your fair share. In fact Diogenes has recently bragged to others that he is going to let you have it! lol.......
Diogenes exact words were "I get to blog about how Prof. Shapiro is scared to death of me" A big LOL!!
> http://sandwalk.blogspot.com/2012/09/athena-andreadis-writes-for-sceintific.html
http://genomeinformatician.blogspot.co.uk/2012/09/response-on-encode-reaction.html
I am glad that both Diogenes and T. Ryan Gregory opted to take down theMayan. This merely illustrates just how productive Shapiro's blogging here has been towards public understanding of science.
I really like how you just jump in and begin calling Mr. Shapiro's fans "delusional" without providing any real counter argument to his evidence. That, in case you don't know, is known as an Adhominem fallacy in the educated world...though it also seems to be verging on a red herring, as well.
If you would stop concerning yourself with sniffing the cracks of Dawkins and Coyne, then you might be able to actually read what Mr. Shapiro says and give a valid critique.
Grow a pair, sir...or go away!
And don't expect an apology from me.
some more stuff for further toughts: what about sleeping and waking up?
Long stretches of DNA once considered inert dark matter appear to be uniquely active in a part of the brain known to control the body's 24-hour cycle
The biologically active material arising from the pineal gland DNA is called long noncoding RNA (lncRNA).
Steven L. Coon, Peter J. Munson, Praveen F. Cherukuri, David Sugden, Martin F. Rath, Morten Møller, Samuel J. H. Clokie, Cong Fu, Mary E. Olanich, Zoila Rangel, Thomas Werner, NISC Comparative Sequencing Program, James C. Mullikin, and David C. Klein, Circadian changes in long noncoding RNAs in the pineal gland PNAS 2012 109 (33) 13319-13324; published ahead of print August 3, 2012, doi:10.1073/pnas.1207748109
Thanks for the reference. It's yet one more example of how we're learning about genome functions that we could not even anticipate a decade ago, let alone 30 or 40 years ago. Science always brings new things up, and it's crazy to think that we ever know enough to make definitive statements.
http://blogs.scientificamerican.com/guest-blog/2012/09/17/junk-dna-junky-pr/
At the end of article the author states: "What the EP results show (though they’re not the first or only ones to do so) is how complex and multiply interlinked even our minutest processes are. Everything discussed in the EP work and in this and many other articles takes place within the cell nucleus, yet the outcomes can make and unmake us."
This newly discovered complexity adds weight to the thesis Shapiro presents in his concept of "A Third Way"
http://www.bostonreview.net/BR22.1/shapiro.html
The introduction gives a clear indication of where he is headed.
"Although such purists as Dennett and Dawkins repeatedly assert that the scientific issues surrounding evolution are basically solved by conventional neo-Darwinism, the ongoing public fascination reveals a deeper wisdom. There are far more unresolved questions than answers about evolutionary processes, and contemporary science continues to provide us with new conceptual possibilities"
"The pervasive but clearly erroneous take-home message of 'a function for everything' harms biology among laypeople by implying ubiquitous purpose. It also feeds right into the perfectibility concept that fuels such dangerous nonsense as the Genetic Virtue Project. Too, it will attract investors who will push sloppy work based on flimsy foundations. Of course, it’s funny to see creationists fall all over themselves to endorse the EP results while denying the entire foundation that gives raison d’être and context to such projects. As for ID adherents, they should spend some time datamining genome-encompassing results (microarray, SNP, genome-wide associated studies, deep sequencing and the like), to see how noisy and messy our genomes really are. I’d be happy to take volunteers for my microarray results, might as well use the eagerness to do real science!"
For you to conclude that "....newly discovered complexity adds weight to the thesis Shapiro presents " is yet another sterling example of the Read Law of Breathtaking Inanity.
Thanks for the additional quote from Dr. Andreadis' article. Her warning "The pervasive but clearly erroneous take-home message of 'a function for everything' harms biology among laypeople by implying ubiquitous purpose", is well worth considering.
However I fail to see how her statement in any way contradicts what I said: "This newly discovered complexity adds weight to the thesis Shapiro presents in his concept of "A Third Way" "
Please explain how a warning about "implying ubiquitous purpose" has anything to do with Shapiro's thesis as expressed in his paper "A Third Way". I realize that you both disagree with Shapiro and support Andreadis' conclusions. However, since her conclusions about the complexity of life as evidenced by the ENCODE project argue IN FAVOR of Shapiro's position, I am puzzled by the final comment in your post.
Thanks for the helpful link to the Scientific American blog. I particularly liked the statement: "Let’s tackle “junk” DNA first, a term I find as ugly and misleading as the word “slush” for responses to open submission calls."
You could have expected a demeaning objection from Kwok. He just does not know how to disagree without making it into a personal insult. A shame because he represents an outdated but useful perspective.
Max Libbrecht from ENCODE stopped by Mike White's Huffington Post blog and left this a few days ago:
"Max Libbrecht from ENCODE and the ENCODE AMA on reddit here. Since I'm mentioned in the comments, I thought I'd put in that I essentially agree with this article: ENCODE did not debunk the idea of 'junk' DNA, contrary to many news outlets. Here is one summary of the true results and their misinterpretation -- there are many others:
http://selab.janelia.org/people/eddys/blog/?p=683
(NOTE TO MODERATORS: This should be posted here since I am reposting a comment by one of the ENCODE scientists who disagrees with Shapiro's interpretation of the results.)
"Sandwalk" (http://sandwalk.blogspot.com/2011/08/physicists-and-biologists.html) August 19, 2011: "Meanwhile, I welcome all those physicists who know nothing about evolution, protein structure, genetics, physiology, metabolism, and ecology. That's just what we need in the biological sciences to go along with all the contributions made by equally ignorant creationists."
I think you have a valid point, Wendell.
Don't you find it just a but over the limit to equate physicists with "ignorant creationists"? This kind of chutzpah illustrates how the "certainty" of conventional evolutionary biologists needlessly offends natural allies in the debates over science education.
"Sandwalk" does indeed state that "...I welcome all those physicists...". However it is obvious that the author intends the statement to be understood as sarcasm. He makes it abundantly clear (especially if you read the rest of his blog) that from his point of view "Interdisciplinary collaboration" is not welcome. This parochial view of science, while perhaps protecting one's own turf, is hardly an aid to scientific progress.
"As a result of ENCODE, Gingeras and others argue that the fundamental unit of the genome and the basic unit of heredity should be the transcript—the piece of RNA decoded from DNA—and not the gene. “The project has played an important role in changing our concept of the gene,” Stamatoyannopoulos says."
This conclusion is in harmony with an earlier blog by Shapiro:
http://www.huffingtonpost.com/james-a-shapiro/dna-as-poetry-multiple-me_b_1229190.html
For example in this blog Shapiro points out:
"Another question is harder to answer: How do multiple messages come to be inscribed in a single sequence in the course of evolution? This is an evolutionary mystery, especially when the second message has a complex structure."
Apparently the meaningful pieces of information do not consist of unedited portions of DNA but are the result of an editing process which produces the pieces of RNA.
Anyone who is interested can see Diogenes' complaints and the evidence he cites on Michael White's blog at http://www.huffingtonpost.com/michael-white/media-genome-science_b_1881788.html?utm_hp_ref=science. Happy reading.
I was the recipient of similar treatment months ago:
http://www.huffingtonpost.com/james-a-shapiro/natural-genetic-engineeri_b_1442309.html
He mistakenly dubbed me a "Neo-Darwinist" advocate, and it took weeks for him to acknowledge the error, after I pointed out repeatedly that I did not endorse the "hard selectionist" view of Coyne and Dawkins. He has asked critics to engage in "respectful" dialogue, especially with creationists, and yet, repeatedly, he has ignored - or condoned - sarcastic commentary by his own fans aimed at critics such as Diogenes and yours truly. Me thinks he doth complain too much when he finds himself at the receiving end of critiques from Diogenes and yours truly.
Just as I do, you expose yourself to responses when you post comments. Sarcasm is OK, but abuse and obscenity are not. I don't mind your critiques because (1) they give me an opportunity to explain my positions more fully and (2) they reveal the quality of your thinking. You rank higher in my view than Diogenes because you have more background knowledge and are somewhat less prone to mischaracterize what I and others have said.
If you read the blog, you'll see that my point was focussed on Diogenes' assertion of certainty. I tried to explain that nothing is ever certain or permanent in science. I specifically said that I did not want to debate the substance of the "junk DNA" notion.
The only comments that get blocked are those that are personally abusive. Diogenes has a problem in that respect. Most of his comments have been posted, even some that transgress the normal boundaries of civil discourse.
As far as I know, all substantive challenges to my positions get posted. I welcome them because they allow us to air the issues more fully. Criticism makes it possible for me to see where my arguments fall short or forces me to articulate myself more clearly.
I have no idea how much of DNA should be classified as "junk" and don't know enough to have an opinion on the matter but I know that the subject matter of the debate is very, very large in detail, very small and has to be addressed in extremely subtle ways often at great expense and effort. The idea that function will be obviously apparent today, with today's knowldge (never mind that of several decades ago), that a majority of "functions" are known, that a far, far larger number of functions aren't yet to be found, likely involving things that look "nonfunctional" today, leads this outsider to be skeptical of the motives for issuing the notice identifying so much of DNA as "junk". It reminds me of some of the more dodgy notices condemning properties to make them available for redevelopment for rather thinly disguised and unstated motives.
If Junk DNA gives you nothing more to study and research; if functional DNA means there's so much more to discover, why would anyone prefer Junk DNA? Why would anyone preach the gospel of Junk DNA with missionary zeal?
I've come to wonder if "Junk DNA" might really just be the lens through which its advocates view everything in their lives… life happens by random accident, life is chaos, life is an accumulation of lucky breaks and useless leftovers.
I also can't help but notice that most of the people I've personally met who espouse this view are flaming atheists, or at minimum hold deep hostilities towards religion. If 90% of our DNA is there for a reason, that seems to suggest they might have to re-think their nihilism.
I think the world's a better, more fascinating place than they give it credit for.
"If 90% of our DNA is there for a reason, that seems to suggest they might have to re-think their nihilism." -- Wrong
"If Junk DNA gives you nothing more to study and research; if functional DNA means there's so much more to discover, why would anyone prefer Junk DNA? Why would anyone preach the gospel of Junk DNA with missionary zeal?"
"I've come to wonder if 'Junk DNA' might really just be the lens through which its advocates view everything in their lives… life happens by random accident, life is chaos, life is an accumulation of lucky breaks and useless leftovers."
Over at Scientific American, blogger Ashutosh Jagalekar has a great post explaining the evolutionary significance of Junk DNA:
http://blogs.scientificamerican.com/the-curious-wavefunction/2012/09/13/three-reasons-to-like-junk-dna/
Canadian molecular biologist T. Ryan Gregory has been blogging about ENCODE too, and this post links to his excellent commentary as well as that of others:
http://www.genomicron.evolverzone.com/2012/09/good-reads-about-encode/
For months, not only yours truly, but others have pointed out to you just how "messy" evolution is, and that it occurs not via "random accident" but instead, by a complex interaction of physical and biological factors interacting with a population, as constrained by that population's prior phylogenetic (genealogical) history. May I suggest that you try finally to understand this?
and then: "it seems to me that many, perhaps most, of the fans of the "junk" idea have an extra-scientific, ideological agenda that permeates what they say"
Given that you self-admittedly know little to nothing about the scientific substance of the issue, how is it you are able to determine that those 'in favor of' junk DNA are merely ideological, while somehow those 'against' junk DNA are not ideological?
Ideology is inevitable. The question is which ideology and how does it affect scientific discourse? The blog was written to indicate what I think are core elements of a truly scientific ideology. Do you have any problems with what I wrote?
Why did you only ask Anthony this question and not others here who are asserting the same thing?