Evolvability: RNA and The Gems of “Junk” DNA


Historically, the central dogma in molecular biology has been that the genetic information in DNA is transcribed into intermediate RNA which are translated into amino acids to form proteins. Proteins were seen as the primary regulators of the expression of genes. While this picture appears to be correct for prokaryotes, a different picture arises for eukaryotes.

Mathematical considerations have shown that while generating complexity is simple, controlling it isn’t. The amount of regulation needed tends to scale as the quadratic of the number of genes. The genome size of prokaryotes seems to be limited by these considerations.

How to resolve the inherent limitation to complexity found in prokaryotes? While genome size for prokaryotes is limited by the need for regulation of complexity, eukaryotes seem to have found a way to increase complexity beyond the limitations of the genome. Eukaryotes have an additional, parallel, system where RNA regulates DNA, RNA, and proteins.

Eukaryotes must have found a solution to this problem. Logic and the available evidence suggest that the rise of multicellular organisms over the past billion years was a consequence of the transition to a new control architecture based largely on endogenous digital RNA signals. It would certainly help explain the phenomenon of the Cambrian explosion about 525 million years ago, when invertebrate animals of jaw-dropping diversity evolved, seemingly abruptly, from much simpler life. Indeed, these results suggest a general rule with relevance beyond biology: organized complexity is a function of regulatory information–and, in virtually all systems, as observed by Marie E. Csete, now at Emory University School of Medicine, and John C. Doyle of the California Institute of Technology, explosions in complexity occur as a result of advanced controls and embedded networking. Sequence-Evolution-Function: Computational Approaches in Comparative Genomics

John Mattick reports on the ‘hidden role of RNA and Junk DNA[1]’ in the October 2004 issue of Scientific American[2].

Mattick Wrote:

A growing library of results reveals that the central dogma is woefully incomplete for describing the molecular biology of eukaryotes. Proteins do play a role in the regulation of eukaryotic gene expression, yet a hidden, parallel regulatory system consisting of RNA that acts directly on DNA, RNAs and proteins is also at work. This overlooked RNA-signaling network may be what allows humans, for example, to achieve structural complexity far beyond anything seen in the unicellular world.

These ideas are of course not without controversy but they would help explain many paradoxes. Such as the C-Paradox, the observation that the complexity of an organism does not scale with the number of protein coding genes.

In my explorations of the concept of evolvability, I have shown that evolvability depends not only on the neutrality of the genotype-phenotype mapping but also on the concept of ‘neighborhood’. Transposons change the traditional character of “neighborhood” of point mutations. This has an important impact on evolvability. While evolution may have ended up in a local maximum under point mutations, transposons can ‘jump’ to higher fitness regions.

The problem with transposons and Junk DNA is that they have remained almost ‘invisible’. New techniques have shown us evidence of many exciting new areas, helping us resolve many of the paradoxes in biology.

And the relevance to intelligent design? Since ID relies strongly on our ignorance, these paradoxes inevitably have led ID proponents to conclude that ‘evolutionary theory’ cannot explain these observations and ‘thus intelligent design’ was invoked. We see that with increased understanding, the gaps in which ID can ‘fit’ are becoming narrower and narrower.

On the other hand we see how the Neo-Darwinian synthesis had limited the variability in the genome to coding DNA. Unaware of the many of the hidden gems. But science moves on and eventually found the hard to detect evidence that may help explain the amount of “junk DNA”. These new findings, rather than limiting evolutionary theory have expanded it, showing the main difference between science and intelligent design when it comes to new knowledge.

Useful resources

  • Junk DNA: “Junk DNA” refers to non-coding DNA, found mostly in eukaryotes. Recent data is showing increasing evidence that some “junk DNA” may have a function after all.

    First of all, it is important to understand the concept of Junk DNA. Junk DNA refers to DNA sequences which are not translated into proteins.

    Of course this does not mean that all junk DNA will have a function, it seems reasonable that pseudogenes for instance will remain historical artifacts.

  • The hidden genetic program of compex organisms John S. Mattick, Scientific American, October 2004 p 60-67
  • Challenging the Dogma: The Hidden Layer of Non-Protein-Coding RNAs In Complex Organisms John S. Mattick in BioEssays, Vol. 25, No. 10, pages 930-939; October 2003.
  • The Unseen Genome: Gems among the Junk. W. Wayt Gibbs in Scientific American, Vol. 289, No. 5, pages 46-53; November 2003.
  • Nowak R. Mining treasures from ‘junk DNA’. Science. 1994 Feb 4;263(5147):608-10.

    The protein-coding portions of the genes account for only about 3% of the DNA in the human genome; the other 97% encodes no proteins. Most of this enormous, silent genetic majority has long been thought to have no real function - hence its name: ‘junk DNA.; But one researcher’s trash is another researcher’s treasure…”

  • Non-genic evolution and selection in the human genome or: “Junk DNA” Gerton Lunter. Good overview
  • Genomic scrap yard: how genomes utilize all that junk. Makalowski W. Gene. 2000 Dec 23;259(1-2):61-7.

    Interspersed repetitive sequences are major components of eukaryotic genomes. Repetitive elements comprise over 50% of the mammalian genome. Because the specific function of these elements remains to be defined and because of their unusual ‘behaviour’ in the genome, they are often quoted as a selfish or junk DNA. Our view of the entire phenomenon of repetitive elements has to now be revised in the light of data on their biology and evolution, especially in the light of what we know about the retroposons. I would like to argue that even if we cannot define the specific function of these elements, we still can show that they are not useless pieces of the genomes. The repetitive elements interact with the surrounding sequences and nearby genes. They may serve as recombination hot spots or acquire specific cellular functions such as RNA transcription control or even become part of protein coding regions. Finally, they provide very efficient mechanism for genomic shuffling. As such, repetitive elements should be called genomic scrap yard rather than junk DNA. Tables listing examples of recruited (exapted) transposable elements are available at this link


Pim, My first reaction was to dish out an adult portion of “I told you so”.

(PZ, you listening?)

But I’m more concerned with keeping Hawaii in the Kerry column.

Make sure you vote on tuesday.


Told whom what?

Here’s my not very radical take on the modern synthesis of evolutionary theory:

Functions encoded in DNA range from essential to useless (i.e. leftover from a previous function: think, e.g. pseudogenes)

DNA coding for essential functions will be highly conserved. DNA coding for optional functions will be less highly conserved. DNA coding for dead or useless functions will be free to mutate (occasionally stumbling upon new functions).

At this point, functions of a small fraction of the human genome’s DNA are understood (at least broadly). Those functions involve (1) encoding the protein and RNA components of living things, and (2) regulatory functions. (There is, of course, nothing to prevent any particular sequence from being involved in both.)

What did your “intelligent design” view predict that isn’t covered by that?

As Russell already commented, rather than restricting the modern synthesis it extends it allowing us to understand why evolution has been so successful. All these aspects add to the concept of evolvability, the ability of the genome to evolve and adapt. While ID proponents such as Dembski have considered this ‘tuning’ of evolution to evolve as a mystery and even as evidence against evolutionary theory, we now come to realize that evolution is just much smarter than the imagination of some. Evolvability, neutral evolution, modularity, robustness, all come together nicely to strengthen regularity and chance pathways. ID may have ‘predicted’ that Junk DNA may have had a function but so did evolutionary theory. While evolutionary theory searched for such function, ID seems to have done little in this area. And finding natural pathways seldomly help the cause of ID which depends strongly on eliminating such pathways, it is not surprising that ID is not in the business of extending scientific knowledge in this manner.

Boy! You guys are good! We are discovering that organisms are more complex than previously thought and this is considered to be more support for the evolutionary theory! Go figure!

One should not confuse complexity with Intelligent Design as the two are quite unrelated. The concept of evolvability is a very fascinating concept as it helps understand how selection shaped the ability of evolution to evolve. In this case, the eukaryotes had to overcome the problem that increased genome size would increase the number of regulators, giving an upper limit to genome size. Eukaryotes found a solution to this by (re)-using RNA. In other words, evolutionary theory is strengthened by these findings. What about ID? well, ID has nothing much to say about these topics anyway

Ah yes! We not only have DNA controlling the development of organisms, but also a hidden, parallel regulatory system consisting of RNA that acts directly on DNA, RNAs and proteins. Yes, evolution is greatly strengthened by such a finding.

Indeed, it shows how some organisms ‘escaped’ the restrictions of the prokaryotic genome size by co-opting RNA. What is ID’s explanation Jeff? Is there any other than arguing that this weakens evolutionary theory when in fact it shows how regularity and chance can explain the genome size in eukarotes?

Yet biologists have long known that RNA does more in a cell than convey protein recipes. For example, RNA strands are important parts of those protein-making ribosomes (SN: 8/12/00, p. 100: http://www.sciencenews.org/20000812/fob1.asp). In fact, some researchers speculate that life began solely with RNA molecules, an idea known as the RNA-world theory (SN: 4/7/01, p. 212: http://www.sciencenews.org/20010407/fob2.asp).

(Biological Dark Matter Newfound RNA suggests a hidden complexity inside cells By John Travis)

The idea that ncRNA would be well adapted for regulatory roles is not new [35, 50, 127]. In the process of defining many of the concepts of molecular genetics, including mRNA and operons, Fran�ois Jacob and Jacques Monod distinguished “structural genes” (such as lacZ) from “regulatory genes” (such as lacI) [128]. A that time, regulators such as lacI had only been defined genetically, and they were known to specifically interact with cis-acting sequences (such as lacO), either at the DNA or mRNA level. Jacob and Monod reasoned that base complementarity would allow RNA to interact highly specifically with other nucleic-acid sequences. They proposed that structural genes encoded proteins, and regulatory genes produced ncRNAs (Fig. 5). Forty years later, their proposal is looking more relevant than ever.

(NON-CODING RNA GENES AND THE MODERN RNA WORLD Sean R. Eddy Nature Reviews Genetics 2, 919 -929 (2001))

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This page contains a single entry by PvM published on October 27, 2004 11:25 PM.

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