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James A. Shapiro

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More Evidence on the Real Nature of Evolutionary DNA Change

Posted: 01/06/12 11:15 AM ET

"Scientific development depends in part on a process of non-incremental or revolutionary change...The usual prelude to changes of this sort is...the awareness of anomaly, of an occurrence or set of occurrences that does not fit existing ways of ordering phenomena. The changes that result therefore require 'putting on a different kind of thinking-cap'..." -- Thomas Kuhn

Conventional wisdom has it that the genetic changes underlying evolution are random accidents, each having a small chance of making incremental improvements in fitness. These ideas came about before we knew about DNA. Now that we have almost 60 years of DNA-based molecular genetics and genome sequencing behind us, a different picture has emerged. As I argue in my June 2011 book, molecular science reveals built-in cell systems for restructuring genomes in times of stress and challenge. The mobile genetic elements first discovered by Barbara McClintock have proved to be everywhere. Sometimes these are also called transposable elements (TEs) because they move ("transpose") from one site in the genome to new sites. They are part of an elaborate set of biochemical functions essential for making changes in DNA sequences (which do not happen without these functions). But the question still remains: does the evidence exist that these same functions are responsible for actual evolutionary change? A recent Nature paper (Lindblad-Toh, Garber et al. 2011) provides some answers.

Investigators from Harvard and MIT's Broad Institute carried out an exhaustive comparison of the human genome sequence with the sequences of 29 other eutherian mammals (the ones that have placenta and diverged from Marsupials). Using state-of-the-art bioinformatic tools, they searched for positively selected features in the human and other 29 genomes. The search identified genetic loci encoding approximately 4,400 out of 13,000 protein families as falling into the positively selected category and are, therefore, presumed adaptively useful throughout eutherian mammals' evolution. While this result was consistent with conventional expectations, the big surprise came when the researchers looked at so-called "non-coding" regions of the genome. These regions contain DNA sequence signals for essential functions, such as packaging the DNA within the nucleus, copying DNA into RNA, replicating the genome, and distributing the two genome copies equally to daughter cells at cell division. "Our data revealed >280,000 mobile element exaptations common to mammalian genomes covering ~7 Mb..., a considerable expansion from the ~10,000 previously recognized cases. Of the ~1.1 million constrained elements that arose during the 90 million years between the divergence from marsupials and the eutherian radiation, we can trace >19% to mobile element exaptations."

A detour will probably be helpful here to explain the term "exaptation" for readers not familiar with it. The word "exaptation" was invented by the late Stephen J. Gould and fellow paleontologist Elisabeth Vrba in 1982 to describe inherited adaptations that have acquired new functions in the course of evolutionary change (Gould and Vrba 1982). It denotes a fundamental aspect of evolution where the jobs encoded by one component of the genome can undergo alteration so that they meet a new adaptive need. Exaptations can occur at all levels of genome encoding, from essential recognition sites to protein coding sequences to entire networks of proteins and the DNA signals they recognize. For example, the same signaling cascade of proteins is used in various organisms to communicate information to the genome about oxidative stress, osmotic pressure, and the presence of suitable sex partners.

As the Broad Institute authors note, "Mobile elements provide an elegant mechanism for distributing a common sequence across the genome, which can then be retained in locations where it confers advantageous regulatory functions to the host -- a process termed exaptation." In other words, new DNA signals in the genome do not need to evolve independently by random mutation at each site where they play an important role. Different DNA signals can be distributed to many sites by the biochemical systems that mobilize defined segments of DNA (mobile genetic elements) to new locations. In this way, evolution of the DNA signals embedded in the genome resembles genetic engineering more than a mutational random walk. The fact is that only fairly recent exaptations can be identified because the traces of the original mobile genetic elements tend to disappear with sequence changes over time. Thus, the >280,000 cases of mobile genetic element exaptation identified in the Lindblad-Toh et al. paper represent the lower limit of genome formatting by a process I dubbed "natural genetic engineering" twenty years ago (Shapiro 1992). Although conventional evolutionists have tended to ignore the importance of mobile genetic elements in evolution -- calling them "junk DNA" (Orgel 1980) -- and treat the well-documented cases of mobile genetic element exaptation as minor and accidental exceptions, the weight of evidence revealed by this article cannot be dismissed so easily.

The idea that mobile genetic elements and natural genetic engineering are fundamental to genome evolution dates back to Barbara McClintock's work on what she called "controlling elements" (McClintock 1987). When she compared controlling elements to the recently discovered repressor-operator system of E. coli (McClintock 1961), her interpretation was widely rejected because DNA mobility was not considered important to the short-term regulation of protein synthesis and genome expression. This rejection notwithstanding, her "controlling elements" terminology now appears prescient in light of recent genomic discoveries. She considered mobile genetic elements as "controlling" elements in the genome because they altered the expression patterns of a particular genetic locus when they inserted into it. This is just what evolution needs to rewire genomic networks at times of evolutionary challenge, especially when similar changes have to occur at more than one locus (McClintock 1956).

There are many eye-opening consequences of the basic role that natural genetic engineering plays in the evolutionary process. We will explore these conceptual changes in future blogs. For the moment, it is deeply satisfying to note that intense genome sequence analysis has validated the work of McClintock and her many followers in the field of mobile genetic elements.


REFERENCES

Gould, S. J. and E. S. Vrba (1982). "Exaptation--a missing term in the science of form." Paleobiology 8(1): 4-15. http://www.jstor.org/stable/2400563 .
Lindblad-Toh, K., M. Garber, et al. (2011). "A high-resolution map of human evolutionary constraint using 29 mammals." Nature 478(7370): 476-482. http://www.ncbi.nlm.nih.gov/pubmed/21993624.
McClintock, B. (1956). "Intranuclear systems controlling gene action and mutation." Brookhaven Symp Biol(8): 58-74. http://www.ncbi.nlm.nih.gov/pubmed/13293421.
McClintock, B. (1961). "Some parallels between gene control systems in maize and in bacteria." American Naturalist 95: 265-277. http://www.jstor.org/stable/2458651.
McClintock, B. (1987). Discovery And Characterization of Transposable Elements: The Collected Papers of Barbara McClintock New York, Garland. ISBN 978-0824013912.
Orgel, L., Crick, FH (1980). "Selfish DNA: the ultimate parasite." Nature 284: 604-607. http://www.ncbi.nlm.nih.gov/pubmed/7366731.
Shapiro, J. A. (1992). "Natural genetic engineering in evolution." Genetica 86(1-3): 99-111. http://www.ncbi.nlm.nih.gov/pubmed/1334920.

 
"Scientific development depends in part on a process of non-incremental or revolutionary change...The usual prelude to changes of this sort is...the awareness of anomaly, of an occurrence or set of oc...
"Scientific development depends in part on a process of non-incremental or revolutionary change...The usual prelude to changes of this sort is...the awareness of anomaly, of an occurrence or set of oc...
 
 
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CrnkyOldMan
I'll accept Co's as people when TX executes one
07:28 PM on 01/09/2012
Great article and amazing stuff. Thanks to the author, James Shapiro, especially for answering comments to further explain the material.
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Junius Gallio
homelessfilker.blogspot.com
10:58 PM on 01/08/2012
So, Professor Shapiro, would it be accurate to say "There is a lot of 'junk DNA' that's actually not junk"?

As for the article, I have to admit it makes a lot of sense: I don't know what portion of a cell's metabolism is involved in copying and maintaining the so-called "junk" portions of the genome, but I do know that keeping useless segments of DNA around seems rather a waste of resources. Knowing that it serves a purpose--especially such an elegant one--is a neat discovery.

Thank you for taking the time to share it with us.
09:20 PM on 01/08/2012
In the simplest possible terms what I believe is being said is that during periods of environmental stress an organism can retrieve "old" but presently "unused" information to make a tailored change in the "active" information resulting in "new" information.

Sorry for the liberal use of quotation marks but viewed this way the words enclosed in quotation marks cannot be viewed by the common definitions. If my synopsis is correct than perhaps this is the very reason that the explanation above is so obtuse...
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James A. Shapiro
10:38 PM on 01/08/2012
Actually, the repetitive DNA can be used to create novel coding and regulatory sequences. Since the repeats are taxonomically specific, each lineage will evolve its own repertoire of novelties. See http://shapiro.bsd.uchicago.edu/ExtraRefs.NaturalGeneticEngineeringAndEvolutionaryGenomicInnovation.shtml for references.
06:37 PM on 01/09/2012
I dare not put this into human terms, but in the terms of say Canis Familriis (household dog) the repeating DNA sequences shared by all of that taxonomy are used differently by the many breeds to achieve novelty and produce rapid, tailored and beneficial change when stressed.

Did I interpret this correctly?

I must also ask: With the continued discovery of variants of the four basic amino acids that we once thought where the sole components of DNA, is it conceivable that the DNA "repeats" have subtle differences that effectively record information of prior periods of environmental stress that are specific to a single variable?
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BillZBubb
It's hot in here: I need more fans!
03:05 PM on 01/08/2012
The concept of "junk DNA" has always been a troubling. Why would an organism continue to maintain large chunks of useless genetic information? Mobile genetic elements may or may not be the correct answer, but it certainly is an intriguing concept and much more satisfying than the "junk" (ie we don't have a clue) concept.

I look forward to future articles.
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James A. Shapiro
04:37 PM on 01/08/2012
In 2005, Rick Sternberg and I published an article on the functionalities associated with repetitive DNA (Shapiro, J.A. & Sternberg, R.v. Why repetitive DNA is essential to genome function. Biol. Revs. (Camb.) 80, 227-50 (2005). PMID 15921050). We identified dozens of important functions encoded by DNA repeats, as did others (e.g. Ugarkovic, D. Functional elements residing within satellite DNAs. EMBO Rep 6, 1035-9 (2005). http://www.ncbi.nlm.nih.gov/pubmed/16264428). Since 2005, there has been much progress in understanding the functional significance of repetitive DNA (http://shapiro.bsd.uchicago.edu/ExtraRefs.DistinctClassesDNAInGenome.shtml). Simply put, the idea of "junk DNA" has no place in serious molecular biology.
05:30 PM on 01/07/2012
In language we laymen can understand, does this article say?:

Life changes as the result of genetic engineering, an intelligently directed, purposeful process, rather than by “natural selection” doing something (???) to random mutations. (genetic accidents).

If that is what the article claims, it is in dramatic opposition to current biological orthodoxy, which insists that purposeful change, or intelligent design, cannot be an aspect of living processes. They even appealed to the courts to ban intelligent design from being mentioned in the classroom. Certainly any form of engineering is by definition a purposeful process, whether the engineer is a deity or some natural intelligence innate to living systems. This has long been a question of bitter controversy, with the defenders of RM&NS accusing anyone question their orthodoxy of being “ignorant biblical creationists”. I’ve been a fan of Dr. Shapiro’s, but I’d hate to see his genetic engineering quietly accepted as a minor alteration in the details of Darwinian evolution. Life is either a mechanical process or it is not. Evolution, defined as descent with modification, was accepted before Darwin. Natural Selection and random mutations were Darwin’s unique contribution.

A Few Autistic Questions about Freud, Marx and Darwin

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blueshield
03:59 AM on 01/08/2012
I certainly won't presume to speak for Dr. Shapiro, or have any authority on the subject, but my understanding is that random mutations are still very much part of the process.

The insight here is that cells ALSO have internal mechanisms which guide non-random genetic changes, and more astonishing, distribute them broadly to multiple loci, where the (potential) advantage can be rapidly adopted, even for dissimilar processes.

That does not suggest 'intelligence', I'm afraid, or design, if by design we mean a known goal or outcome was purposefully intended.

But it does suggest that life is more capable of responsive adaptation for survival than we'd previously assumed, and not just a passive reliance on chance.
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Counterglow
Werner Heisenberg may have been right.
11:59 AM on 01/08/2012
Thanks for saving me the trouble. And you were probably more diplomatic about it that I'd have been, too.
nanjemoy
first, check your satire-o-meter.
12:40 PM on 01/08/2012
That's not my read. I think it says that within the DNA are genes that are mobile, and may do things to the DNA itself, specifically when the species is under stress.

This isn't unusual as a general idea - if you consider the mammalian diving reflex, for example - there are many abilities that creatures possess that are only invoked during certain conditions. But I don't think it's usually applied to the altering of DNA itself.

It has been long believed that many parts of human DNA are "doing nothing" or vestigially carried over, without any particular purpose in forming the person. This is the idea of Junk DNA.

I think this article is not suggesting that random mutation doesn't exist, but that other controlling factors within the DNA can also change it.
08:17 PM on 01/06/2012
I KNEW IT, I KNEW IT! I knew I was witnessing intelligent self design right before my very eyes, and that on a genetic evolutionary level! That was ULTIMATELY THE ONLY WAY to explain the SIZZLING advancement of mankind over the past several centuries. Evolution HAS to be more than random chance, and now they are basically proving it. I can't tell you all how much this has NAGGED, yes, repeatedly, TOTALLY NAGGED my brain (via my subconscious) for years now! Thank you, geneticists! - Rick Carter

(PS - We need to carefully look for a downside to this, if only among a limited segment of the population. Trust me, "downsides" happen very frequently, and can really sneak up on you from behind.) - RC
02:00 PM on 01/06/2012
Breezed through the paper, and I'm still confused about what you're getting at in implying that the alus, lines, et al. aren't being inserted randomly, or nearly randomly (in the case of preferential insertion sites). I've always understood that rearrangement of these elements is rare in mammals, and random, or essentially random. It's always been understood that insertion is one mechanism of mutation. Please clarify.

Its great that you list the references, and I hope this will be common practice on Huffpost Science. Too many science news articles fail to give anything beyond an author's name. Ou, the names on this article. I obviously don't look at alot of big science papers because this is the first time I've ever seen something like "Baylor College of Medicine Human Genome Sequencing Center Sequencing Team" listed as an author.
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James A. Shapiro
06:59 PM on 01/06/2012
Mike, The action of the mobile genetic elements is non-random in at least three ways: (1) the same DNA element is moved each time, distributing the same signals and coding sequences; (2) exactly when the mobile elements move to new sites is regulated by cell or organism responses to life-history events; and (3) insertions occur non-randomly in the genome. You can find out more about all these features of genome change in my book or by looking at the online bibliographies associated with it at http://shapiro.bsd.uchicago.edu/evolution21.shtml.
Happy reading, Jim.
12:51 PM on 01/06/2012
It looks like our understanding of how evolution operates is going to undergo some radical changes. Physics underwent a revolution about a century ago. Perhaps it is now biology's turn for such a revolution.
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CSKAP
Morlock or Eloi?
12:18 PM on 01/06/2012
Funny how God makes these things happen so we somehow believe that evolutionary theory is correct.
And he seems to do it over and over again.
What a kidder
I recently asked a good evangelical friend to explain fossils.
She said it was easy “God put them there”
Well, you can’t argue with that.
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Tim Kunk
Aimlessly wondering the information highway.
03:19 PM on 01/06/2012
In his book, it is also claimed that pi=3, that doesn't do to well.
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James A. Shapiro
07:02 PM on 01/06/2012
Master Chief, Whether it's God or Nature or whatever you want to call it, figuring out how evolution occurs and marvelling at the amazing way living things change themselves over time is a great intellectual adventure. All are welcome aboard as long as they have the right spirit of discovery.
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UnderTheHedgeWeGo
Show me some evidence.
12:20 PM on 01/08/2012
Is there ANYTHING in this research that would lead one to believe that there is anything supernatural or guided by a cosmic intelligence in the process you describe? I'm not asking "might it be" I'm ask "Is there any reason to believe it is". To me it sounds like one more interesting biological process derived by the power of evolution over deep time.