November 25, 2003
Junk DNA Result Of Slowness Of Natural Selection

Species that replicate at a slower rate and that are fewer in number do not experience enough selective pressure to prevent junk DNA from accumulating

Genetic mutations occur in all organisms. But since large-scale mutations -- such as the random insertion of large DNA sequences within or between genes -- are almost always bad for an organism, Lynch and University of Oregon computer scientist John Conery suggest the only way junk DNA can survive the streamlining force of natural selection is if natural selection's potency is weakened.

When populations get small, Lynch explained, natural selection becomes less efficient, which makes it possible for extraneous genetic sequences to creep into populations by mutation and stay there. In larger populations, disadvantageous mutations vanish quickly.

Most experts believe that the first eukaryotes, which were probably single-celled, appeared on Earth about 2.5 billion years ago. Multicellular eukaryotes are generally believed to have evolved about 700 million years ago. If Lynch's and Conery's explanation of why bacterial and eukaryotic genomes are so different is true, it provides new insights into the genomic characteristics of Earth's first single-celled and multicellular eukaryotes.

A general rule in nature is that the bigger the species, the less populous it is. With a few exceptions, eukaryotic cells are so big that they make most bacteria look like barnacles on the side of a dinghy. If the first eukaryotes were larger than their bacterial ancestors, as Lynch believes, then their population sizes probably went down. This decrease in eukaryote population sizes is why a burgeoning of large-scale mutations survived natural selection in the first single-celled and multicellular eukaryotes, according to Lynch and Conery.

To estimate long-term population sizes of 50 or so species for which extensive genomic data was available, Lynch and Conery examined "silent-site" mutations. Silent-site mutations are single nucleotide changes within genes that don't affect the gene product, which is a protein. Because of their unique characteristics, silent-site mutations can't be significantly influenced by natural selection. The researchers were able to calculate rough estimates of the species' long-term population sizes by assessing variation in the species' silent-site nucleotides.

Of the original group of sampled organisms, Lynch and Conery selected a subset of about 30 and calculated, for each organism, the number of genes per total genome size as well as the longevity of gene duplications per total genome size. They also calculated the approximate amount of each organism's genome taken up by DNA sequences that do not contain genes.

The researchers found that a consistent pattern emerged when genomic characteristics of bacteria and various eukaryotes were plotted against the species' total genome sizes. Bigger species, such as salmon, humans and mice, tended to have small, long-term population sizes, more genes, more junk DNA and longer-lived gene duplications. Almost without exception, the species found to have large, long-term population sizes, fewer genes, less junk DNA and shorter-lived gene duplications were bacteria.

The data suggest it is genetic drift (an evolutionary force whose main component is randomness), not natural selection, that preserves junk DNA and other extraneous genetic sequences in organisms. When population sizes are large, drift is usually overpowered by natural selection, but when population sizes are small, drift may actually supersede natural selection as the dominant evolutionary force, making it possible for weakly disadvantageous DNA sequences to accumulate.

Junk DNA costs energy to duplicate and to carry around as part of each cell. So natural selection operates against it. But if junk DNA gets generated by errors in replication faster than natural selection can select against it then junk DNA can accumulate..

At some point in the 21st century, barring some natural or human-caused disaster, biotechnology will advance far enough to make it possible to edit out junk sequences from cells. So it should become possible to have offspring that have far fewer junk DNA sequences. Therefore junk DNA may eventually disappear from the human species. Also, replacement organs will eventually be genetically enhanced with more beneficial variants of genes that play important roles in each organ type. It seems reasonable to expect that at least some people will opt to have their DNA edited to eliminate junk DNA sequences from cells that will be used to grow replacement organs. So even some of us who today are walking around with junk DNA will have less of it once we are able to have replacement organs grown for us.

Update: Carl Zimmer raises a number of specific objections against the idea of removing junk DNA but he also sees one point in favor of doing so: some junk DNA sections can hop around the genome and cause mutations when they embed in new locations.

There are also arguments for getting rid of junk DNA that Futurepundit doesn't mention. When mobile elements jump around to new homes, they can trigger diseases as they mutate the genome.

As for mobile elements that jump around the genome: Yes, note that this reason for removing junk DNA is especially strong in the case of stem cells that are going to be used to grow replacement organs. The cells in those replacement organs (with the exception of testes and ovaries) are not going to have their DNA passed along to progeny and therefore the ability of their junk DNA to mutate to create new environmental adaptations provides no benefit while the junk DNA does pose a mutational threat that can result in cancer and other diseases.

The effects of removing various junk sequences will be testable by producing organs without them and then seeing how those organs perform. This will be relatively less risky to experiment with in the case where humans have two of an organ. So, for instance, one could have just one kidney replaced with a junk-free kidney and then, with the other kidney still available as back-up, the functionality of the junk-free kidney could be monitored over time. The same could be done with many muscles. Replace a thigh muscle with a junk-free thigh muscle. If the thigh muscle fails the result is unlikely to be fatal. There would still be risks from such an experiment as one could imagine fatal failure modes where, for instance, an organ releases toxins or clotting factor or something else that damages some other more critical part of the body.

Next he raises the point that what seems like junk DNA might not really be junk DNA.

Junk-free genomes may indeed become possible in the future, but they're probably not a wise idea. Even if junk DNA doesn't benefit us in any obvious way, that doesn't mean that we can do without it. Many stretches of DNA encode RNA which never become proteins, but that doesn't make the RNA useless--instead, it regulates the production of other proteins. Some broken genes (known as "pseudogenes") may no longer be able to encode for proteins, but they can still help other genes produce more of their proteins

Well, my response to this is pretty simple: Yes, it is hard to be certain that some DNA section has no benefit to the cell. But suppose at some point in the future we can assign a really high probability to the idea that some chunk of DNA has no value and that it actually is far more likely to cause disease than benefit? Why not then remove it?

This reminds of another point: Some genetic theorists make the argument that we each have dozens and perhaps hundreds of purely harmful mutations because natural selection can't select out hamful mutations as fast as they are generated by mutations that occur during reproduction. If this argument is correct (and I believe it is) then we should also have junk DNA that is either of no value or harmful. Someone who holds this more pessimistic view of our genomes as full of flaws and parasitic DNA sections is going to tend to be more willing to decide to throw out the suspected junk with the view that the odds are great that the suspected junk really is junk. Of course, there's no rush here and we ought to wait a couple of decades for a lot more evidence to accumulate before acting on this belief.

Zimmer also brings up the argument that simply by making the genome bigger that junk DNA may serve a useful function by making cells the correct size. I'm skeptical of this argument mostly because an assortment of different kinds of intracellular components cross-react with each other in undesirable ways and turn into compounds that the cell can not eject or destroy. As a result, cells accumulate junk and this junk accumulation robs the cells of needed space and decreases the efficiency of cells as they age as well. The junk also serves as a source of free radical generation. This problem with junk accumulation has even led Aubrey de Grey to argue for the transfer of lysosomal enzymes from other species into humans as a rejuvenation treatment. Analogously, genomal junk is taking up space that could be used by cells to do useful work. Get rid of it and the cells might become ever so slightly more efficient.

Next Zimmer brings up the value of junk DNA and, in particular, pseudogenes, as potential sources of future beneficial mutations:

It's on this evolutionary scale where purging junk DNA makes the least sense. The pasting and copying of junk DNA is a major source of new genetic variation. Instead of changing a nucleotide here or there, mobile elements can shuffle big stretches of DNA into new arrangements, taking regulatory switches and other genetic components and attaching them to different genes. While some of this variation may lead to diseases, it also prepares our species to adapt to new environmental challenges. (Similarly, pseudogenes that are truly broken still have the potential to become working genes again. Some scientists have proposed calling them "potogenes.")

Here's my problem with that argument: Natural selection is going to cease to be the major source of new beneficial mutations in humans within 20 or 30 years. We are going to have our genomes changed by bioengineering. Therefore junk DNA will have no value to us. Going into future centuries our bioengineering techniques will advance even further and we will be able to simulate the effects of variations orders of magnitude more quickly than mutations occur naturally.

There's another point about junk DNA that especially holds for agricultural plants and animals: to the extent that junk DNA can be removed from crops and livestock a source of variability is removed that essentially serves as noise. If someone develops some ideal dairy cow and wants to clone it he does not want jumping genes creating variations that cause some of them clones to produce less milk. Similarly, jumping genes could create variations in the growth of corn or wheat that would be undesirable.

It should be possible to grow up replacement organs in other species first and to try out junk removal in organs and whole genomes in other species before trying it out in humans. This will provide an important way to discover functional purposes served by parts of genomes that are mistakenly thought to be junk. The mechanisms by which those parts serve useful functions will then be able to be searched for in humans as well. In my view, the discovery of which sections of the genome really are junk is a technical challenge that will be solved with time. Once purely junk sections are identified with a fairly high probability of correct classification and techniques for removing it are developed it seems inevitable that more daring individuals will opt to try to have the junk removed from their replacement organs and progeny.

Share |      Randall Parker, 2003 November 25 01:39 AM  Evolutionary History


Comments
Zach said at November 25, 2003 7:24 AM:

Why would we WANT to have junk DNA edited out? Sure, it may be evolutionarily untidy and inefficient but we still don't know for sure what all the junk DNA does if anything. The length of the DNA itself may be an important variable and altering it could cause unintended long term effects. There may be some interaction between genome length and the extra genomic information found in the proteins around the nucleotides. Some of it (the non repeating parts) may code for snRNAs which don't get translated but could be useful for regulation. Anyway, that's all beside the point because unless there is a benefit for reducing junk DNA, there is no reason to remove it.

Bob Hawkins said at November 25, 2003 8:16 AM:

Maybe, instead of removing junk DNA, people will have it replaced with DNA that is still biologically junk, but codes for something of interest to them. The complete recordings of the Rolling Stones, say. Spies will replace microfilm with junk stretches of their DNA. Genealogy buffs will pass on their family tree to their offspring. Librarians will carry the library with them. The possibilities are endless.

Kevin said at November 25, 2003 1:25 PM:

Bob Hawkins' idea has already been the subject of a story which appeared in either ASIMOV'S or ANALOG some time ago, probably in the late 1990s. In the story, Muslim hajjis on their way to Mecca visit a genetic engineer traveling with the pilgrims who encodes the text of the Koran into his customers' DNA; I don't recall whether he wrote it into junk DNA or introduced a virus or bacteria with the text of the Koran in its DNA.

The plot hook in this story was that this allowed the creation of a disease which targeted Muslims who'd made the Hajj and skipped over everyone else; alternately, such a marker could be used to create a disease to which Muslims were immune.

Fly said at November 25, 2003 2:57 PM:

Bacteria regularly exchange genetic material, e.g. conjugation, plasmids, and phages. In some sense the bacterial "genome" might be viewed as all the shared genetic material. I'm guessing that this shared "genome" is large and includes significant junk. (Hmmm...bacteria use a P2P file-sharing system for genetic storage.)

On a different note, the evolution of multi-cellular life may have been significantly aided by "junk" DNA. Less selection pressure at the DNA level could allow "superfluous" duplicate genes whose mutation then led to new specialized proteins. Bacteria may be too optimized to evolve significantly. Several inefficient "backward" steps might be required to find a better path. Too much efficiency at removing "junk" could prevent the better path from ever being followed. The "inefficiency" that led to our "junk" DNA could have provided the freedom for multi-cellular life to evolve quickly.

Of course the conservation of some "junk" DNA between the genomes of different species implies that "junk" DNA is playing an important (but unknown) role. Not all "junk" is junk.

Randall Parker said at November 25, 2003 3:43 PM:

Fly, I don't think that junk DNA is going to have any future useful role in human evolution because we are going to start engineering our progeny. FuturePundit prediction: We will change more genetically in the next 100 years than we changed in the last 10,000 years.

Zach, Any DNA that has a function is, by definition, not junk DNA. Yes, we are faced with the need to determine that suspected junk DNA really is junk and really serves no purpose at all in any way whatsoever. Admittedly, that is hard to prove. But suppose we can approach a high degree of certainty that some stretch of DNA can be safely removed without causing any detrimental effects. That will save each cell space and reduce a resource drain.

Also, as has been pointed out, junk DNA can be replaced with sequences that do useful things. One big addition I'd like to be able to make to my own cells would be add genes that code for lysosomal enzymes that can break down accumulated intracellular garbage that our current lysosomal enzymes can not break down. Such genes could probably be added on top of all the DNA sequences we already have. So it is not absolutely necessary to get rid of the junk. But the attraction of genome optimization by cutting out the junk will appeal to some of us who like to improve designs even in areas which are not that important. Since the idea appeals to me I figure I'm not alone.

Fly said at November 25, 2003 5:26 PM:

Yep, modern biotech makes natural evolution obsolete.

Cultural evolution has surpassed genetic evolution for at least twenty thousand years. Better tools and better software running on the same old hardware. Now cultural evolution has created the tools for upgrading the biological hardware. Should be an interesting future...

Zach said at November 26, 2003 7:57 AM:

Randall,
I see your point about "junk" being junk.. I suppose if that's true it renders my argument false. Getting to that point may not be so easy in my opinion. As we have seen since Watson and Crick, everytime we think we know the secrets of the genome, something new pops up by some genius researcher (snRNAs, extragenomic information). I think alot of knowledge can be gained from computer modeling as in the article. That is probably the best way to determine what has accumulated and inefficient. I still don't see the benefit of removing useless information -- mostly because proving it is useless is difficult and maybe impossible.

Bob Badour said at November 26, 2003 8:25 AM:

It might make sense to focus on harmful mutations and unstable junk specifically. I can see someone saying "This chain probably does nothing, but if it mutates as it often does, it might cause some disease I do not want. Cut it out!"

Francisco Lajarín said at December 1, 2003 7:41 AM:

The point is if we will have full and complete knowledge of how DNA works, so we can say what is "good junk" and what is "bad junk" (if there is such a distintion). Hundred years ago nobody knew the current state of Science, so I think is too speculative anticipating is someone will get rid of bad junk DNA in 200 years.

Pandor's Box said at September 8, 2004 12:22 PM:

I think leaving genetic engineering up to those who only have just began to even understand what they are looking at is a formula for error. This type of hypothesis sounds like a bad sci-fi movie and shows why it should be quite concerning. You think intentionally removing junk DNA is the future for genetic natural selection? That seems to be the trend a lot in science and medicine is just because you don't understand what it is does not mean that nature or the real designer has purpose and knowledge of what it is for. Thanks to mans manipulations of science we have Chemical Weapons, Biological Weapons, Nuclear Weapons, Aids, Eugenics, Abortion and a list of many adverse causes. I just picture a bunch of mad scientists who justify what they do for good getting out of control and destroying most of life. All because they lack faith.

Silent Philosopher said at November 7, 2004 6:58 PM:

What about microRNA, eh? Doesn't code for genes, but without it very nasty things can happen (in plants, for instance, their leaves won't grow right) Say it with me, "If it ain't broken, don't fix it!"

Tahir Mansoori said at October 22, 2005 11:57 AM:

Are there any studies, leaving out junk DNA to make DNA mostly useful in protein productions. I was reading at http://en.wikipedia.org/wiki/Noncoding_DNA

Recent evidence suggests that "junk DNA" may in fact be employed by proteins created from coding DNA. An experiment concerning the relationship between introns and coded proteins provided evidence for a theory that "junk DNA" is just as important as coding DNA. This experiment consisted of damaging a portion of noncoding DNA in a plant which resulted in a significant change in the leaf structure because structural proteins depending on information contained in introns was incorrect.

Vermouth said at January 11, 2006 7:35 AM:

What needs to be determined obviously is that junk DNA really is junk. Most of you speak in horror of this as if the actual experimentation is going to be done on you. Hell no, that's what plants and laboratory test animals are for. Sure it may be determined that what once was thought of as a junk sequence may in fact do something useful after all and this will also be brought to light through experimentation. But I like the idea Randall Parker suggests; that junk DNA sequences can be replaced by DNA that is not junk and is in fact useful and serves a purpose like code for lysosomal enzymes and break down intercellular garbage. If we want to make modifications to the genetic code, what better place to start than the junk sequences that seem to be nothing more than place holders for now. Let's make some use of this undeveloped territory.

Mike Umina said at January 11, 2006 8:17 AM:

I have often wondered about the function of junk DNA. However I think it is much more usefull to design and repair the DNA we DO know the function of. At some future time we may understand the code and reasons for it as arranged by the Master Programmer Himself. We find new cellular structures and interactions often now, and orders of magnitude of microscopy size are showing new things constantly. It's kind of like a fly landing on an Ocean Liner and saying all we really need is the engine, whats all this extra garbage for? We as humans may yet find that some of it is necessary for functions we have not developed yet, or been called on to perform in ages. The genetic variation manifested in humans has already been shown to enhance or decrease our survival to external influences, like sickle cell anemia providing resistance to Malaria, and other genes causing resistance to diseases like the black plague. Our junk is the accumulated "closet" of our available, and sometimes emergency, patches to our genetic program. Granted, some of it has not been needed in thousands or millions of years, but remove it, and who knows what will happen. I would rather update and patch things like Microsoft does, a bit at a time as deficiencies are found and re-engineerd. Once the way to update DNA is perfected, new updates can be done as needed and the knoweledge base allows. Plus, no one has adressed the possibilities of secondary ot tertiary or higher level effects of junk DNA interactions. So much of this junk DNA may code in as a spacer, determining the size of your big nose, or even as a correct placement holder for extra room needed for proper functioning of RNA or DNA replication or repair. It must be anthropormorphic bias that makes us think that we understand how everything is done when we have only seen the tip of the iceberg. It can have Titanic results. Fools rush in, as they say, where angels fear to tread. It is hard for us as Humans to think of things in any way but in human terms. It will get us in a lot of trouble if we are not careful.

Steve Johnson said at January 29, 2010 3:16 PM:

Don't we use junk DNA to determine a male and female relatedness of family? As a male with y-dna/junk dna... it has survived mutations caused by viruses over many generations and I personally would like those mutations to be passed down through the generations of my descendants so they know where they came from...The genome has been mapped and found that our genome is indeed virus based, it is what makes us who we are... so, there is a possibility that if you remove junk DNA you remove a protective code of survival then we all die at a faster rate then to put the junk DNA back. Or, we will all be clones of each other with no junk DNA that makes us seperate from each other. I am my ancestors as my descendants will be me...R1b1b2a1a1d* if anything I will put my alles on the back of my tombstone and my Haplo on my death certificate so future generations will know where they came from and continue to survive based on previous historical mutations from disease and viruses... or go ahead and clean the slate and start over..."Natural selection is going to cease to be the major source of new beneficial mutations in humans within 20 or 30 years. We are going to have our genomes changed by bioengineering."... I sure hope not...

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