11 July 2010

Introns. Let's think about this, people. Part IV.

So why is it that I and many other biologists hypothesize that introns are mostly non-functional?
(I'll assume that you've read the previous posts, and that you understand what it is that I mean when I challenge claims that introns are functional elements in an information-rich genome. And to avoid confusion, I'll speak only for myself, although I surmise that a tiny minority of biologists would agree with creationist characterizations of the human genome.)

Here are the basic data that lead me to conclude that intron sequences are mostly dispensable for biological function. I've provided links to key references, and we can go into more detail in further posts or in the comments.

1. When we compare genomes from similar types of organisms, we see that coding sequences are highly conserved, meaning that these sequences are very similar in the different organisms. But the intron sequences tend to vary considerably, both in length and in sequence. These variations do not generally correlate with organismal complexity or functional innovation. I surmise that introns can be changed significantly without affecting development or function, and I conclude that this is because most intronic sequence is of no functional value.

2. When genomes from very similar types of mammals are compared, introns appear to be lost frequently but almost never gained. Loss of introns occurs in a pattern that suggests a specific mechanism for the deletion, and the losses do not result in known functional deficits. I surmise that the mere existence of many introns, never mind the sequences they harbor, is dispensable for development or function in mammals. (Intron loss is common in other animals as well.)

3. When genes within the same organism are compared, those genes that are most highly expressed (the ones that are used the most) have the shortest introns. (See analyses in chicken and nematode and human.) I surmise that introns tend to be a burden on genetic machinery, such that natural selection acts to favor compactness in oft-used genes, by favoring shorter introns. And I conclude that intron sequences are thus of little consequence, noting that the most heavily used genes are the genes with the least intron sequence.

4. When we examine animal genomes that are notable for their small size, and compare them to animal genomes of average or large size, we see that introns are dramatically reduced in size while coding sequences remain roughly constant. The variations do not correlate with organismal complexity or functional innovation. I surmise that because downsizing of genomes leads invariably to downsizing of intron space, much of the content of intron space is dispensable for development or function in animals.

5. When we examine the genetic causes for various diseases or traits, we find mutations in coding sequences, or mutations that alter splicing, or mutations that affect genetic control regions, far more often than we find mutations in introns. (Take a stroll through the OMIM database; pick your favorite human disease and try to find intron mutations.) This despite the fact that intron space is at least twenty times the size of coding space and vastly bigger than the genomic space allotted to splice codes and control sequences. I surmise that most of the changes that really matter are changes to genes and their expression; mutations in introns are almost always inconsequential.

6. Genetic experiments over the last three decades have shown that, with rare exceptions, the genetic deletion of a gene (by disruption of one or more of its coding regions) can be corrected by re-introducing the coding region alone into the organism. (Here's a recent example from a mouse experiment, chosen from scores or hundreds in the literature.) In other words, a mutant organism in which gene X has been inactivated can be "rescued" (made largely normal again) by the insertion of the coding sequence of gene X without introns. I conclude that intron sequences rarely harbor significant functional information, which is far more likely to be found in coding sequences and control regions.

7. Transposable elements – those weird genomic players that can jump around in genomes – are far more common in introns than they are in coding regions. The implication is that introns are much more tolerant of such messing around than are the coding sequences. I surmise that intron sequences are rarely relevant to biological function.

Conclusion: intron space looks like a junkyard to me. At least in medium-sized genomes like ours, I see little evidence that introns are streamlined, efficient, functionally-critical information repositories. I see them as messy collections of evolutionary debris, harboring lots of interesting functional bits but largely consisting of flotsam that is as likely to cause dysfunction as it is to lead to evolutionary opportunity.
Next and final post in the series: some ideas for experimental tests of the assertions of design theorists who posit that introns are characteristics of genomes that are "dominated by sequences rich in functional information."


SWT said...

Thanks for another clear discussion of a messy topic.

I'm not surprised, based on my amateur's understanding of biology, that most introns seem to be completely dispensable; what I find surprising is that changes to some of them do have an effect. Is this possibly the result of gene overlap -- that a sequence that is critical in one gene is within an intron in an overalapping gene? Or that an intronic sequence has developed a regulatory role?

Justin Topp said...


Good arguments, but I must say that #1 and #5 are the weakest of the 7. Especially 5, since most people that have been looking for mutations have been focused on coding regions solely.

Is the overall argument from this group of posts simply that all introns don't have to be a priori functional? I think that we will certainly see more functional in the future and would not want ID folk to believe that evolutionists like us are scared by this. The simple truth is that introns were not thought to be all that interesting so they were largely ignored. Now we've some functional significance. Not a lot, but some. Will we see more in the future? Probably. Does that mean we're designed? Hell no.

guest said...

Countdown to Meyer-cheerleading post from Cordova in 3-2-1....

John Hansen said...

So I have followed this discussion with some interest from the original open letter to Stephen Meyer. In general, I find your arguments have a plausible nature to them. But they are hardly the nail in the coffin that was advertised.

One thing I continually notice about human beings. The ease with which we are swayed by confirmation bias. I know this applies to me as well as to my opponents, so we all need to be a little less certain of our results, a little more open to questioning and doubt.

The idea that introns basically have no functions is an absolute statement. This is of course a dangerous position because it is, in the final analysis, still an argument where the primary evidence is lack of evidence. What I am still trying to figure out is what is it that prompts such invective from our esteemed host. The bite to his comments seems to go way beyond the extent of the evidence for his case.

John Hansen said...

OK so I'll take this toned down statement at face value. But then he should also back off of the demagogic name calling he practices in. After all, if we are correct about the things we seem to agree on ( Steve, me, SWT, and Meyer ) we are going to be spending an awfully long time together in the place where all the questions will be resolved. Like I said, its not that the evidence is not plausible, its just that it does seem to make it to the standard that you must be a liar or incompetent ( a false dichotomy ) if you don't accept it.

chunkdz said...

Hansen, give me one good reason why Steve should not rip out your still beating heart and eat it in front of you right now. You've got some balls climbing aboard a vessel flying the jolly roger and spouting such inflammatory IDiocy.

SteveMatheson said...

chunkdz, you are now officially a troll. Further idiocy of this sort will be deleted, at least until I get a Troll Dungeon set up into which I can dump your nonsense. Comments of any other sort are still welcome, but this is your first and only public warning about trolling.

SteveMatheson said...

John, I do not identify people as dishonest or incompetent for merely not "accepting" evidence or explanation as convincing. Your point about confirmation bias is a good one, but don't ruin it by misconstruing my criticism of the DI or others. Check out this old post of mine, on the dishonesty of Reasons To Believe, for explanation of the clear difference between disagreement and dishonesty.

SteveMatheson said...

Hi Justin--
most people that have been looking for mutations have been focused on coding regions solely.
I'm not sure that's true. GWAS studies make no such assumption, nor do most or all other genome-level analyses.
Is the overall argument from this group of posts simply that all introns don't have to be a priori functional?
No, the overall argument is that intron space ought not be assumed a priori to be functional, i.e., that the hundreds of millions of base pairs of the human genome contained in introns should not be assumed to contribute to biological function.

SteveMatheson said...

Thanks for reading. The previous post discussed the kinds of functional elements that are found inside introns, and changes to those elements can and do have effects.

chunkdz said...

Ok, Steve, I apologize. If you can lower the skull and crossbones I suppose I can put away my saber too. Truce.

[But you were definitely more fun when we were fighting together against the "dangerous cancer" of "mendacious", "idiotic", "creepy", "silly", "confused","integrity lacking", "profoundly misleading", "political propagandists", "enemies of science", "idiots", "liars", and "bottom-feeders" from the "wholly corrupt" "intellectual ghetto" known as "the cesspool". Those were good times, no?]

Also, in all sincerity, thank you for some very informative and easy to read posts on introns. Very much looking forward to the final post. I won't bother you further unless it is to ask a question about cell biology.

Also, sincere apologies to John Hansen with hopes that he did not think I was being literal. I never comment solely with the intent to inflame.

John Hansen said...

Steve, I read the linked post on why you consider RTB to be dishonest. Not impressed. Your claim of dishonesty still has more to do with shades of meaning, short-hand speech, objections to straw men etc. More often than not you don't like the strength of the assertion made, and don't like the character of the evidence put forward. Typically, I find a certain plausibility to your arguments, but they simply are not the "nail in the coffin" type argument that you claim, and mostly, your conclusions seem to rest upon a kind of circular reasoning. If you start committed to your view of God and nature, you will consider the arguments of the other side to be duplicitous. But from the other side, the conclusion that Rana is dishonest and not disagreeing seems more to do with subjective belief than objective truth. I think some of his language is unfortunate and could be better qualified to be precise, but I do not believe it is generated with a deliberate desire to deceive. This is a hard thing to prove.

OTOH, I think I spotted in your article a glaring error. You ridicule the idea that God created dinosaurs to give us petroleum. I assume your ridicule means that you find it easy to prove that Rana is wrong in this belief. But I doubt you have one good reason why this statement has to be false.

We are in shaky ground when we argue "why" about anything that the Lord does. His word even says His ways are past finding out. So why would you ridicule a human theory about why God did something unless you have good reason.

Now I have good reason to suppose that God meant there to be reserves of cheap energy present in the world. Can you come up with one good reason why the idea should be ridiculous.

In God's word, which claims He knows the end from the beginning. God gives the Revelation to His Apostle John. John obediently writes that the dead bodies of the two witnesses will lie in the street of Jerusalem for three days, the whole world will see this, and the the nations will celebrate it. Now this must have seemed preposterous in John's day. There was no way in John's day that "the nations" could "see" anything that occurred in only three days. Yet John dutifully wrote what he heard.

Because we have the cheap energy that fueled industrialization, we have no problem today with the whole world seeing a single event and communicating about it. Thus in order for the Revelation to be true, God needed to provide some source of cheap energy to man.

What is your good reason that the above is worthy of scorn?

John Hansen said...

Again the you make the overly harsh statement. The rest of my comments are not a "train wreck". This is just simply over the top rhetoric and uncalled for. I am not trying to pettifog by discussing dinosaurs and petroleum. I am not trying to prove it true. I am only saying that I have good reason to believe that God intended there to be cheap sources of energy around in latter days. The current theories of the natural sciences is that the existence of the dinosaurs is why we have petroleum.

You on the other hand have no basis but personal credulity for thinking Rana's idea to be silly. I am not trying to make a big intellectual point here from what was obviously a throw away line and not part of your main argument. I was only pointing out that world view sometimes blinds you from seeing the thought patterns of the others. I think your consideration of this may lead you to a more charitable view of your brethren, and less flying of the Jolly Roger.

kakapo said...


I don't know about scorn, but the following are problems with your "dinosaurs are required to fulfill Revelation" theory:

1) Your particular interpretation of that passage has not been widely held through church history. (Dispensational pre-millenialism is of 19th century origin if I remember correctly.)

2) God does not require cheap energy to inform the world in 3 days. e.g. the flying scroll in Zechariah.

3) For the oil fulfills Revelation story to be true, Jesus needs to hurry up since there won't be any left in a few hundred years.

4) Dinosaurs were almost certainly not the source of petroleum. It's far more likely to be marine life, and just based on biomass arguments, microscopic (e.g. algae, plankton, etc.)

These are just off the top of my head. I could likewise think of many reasons why God might not have wanted humanity to have oil but I digress on something that is already a digression as Steve noted below.

John Hansen said...

kakapo -
1. Revelation - was clearly written as prophecy. I would not doubt that many people before the 19th century would not interpret that passage that people would literally "see" the dead bodies in the street. In the context of 19th century realities, it would not make sense for the whole world to "see" ( and that is the literal meaning of the Greek word in the passage ). Besides your argument is not really a good argument anyways. ( see Appeal to Popularity )
2. The Greek verb does not say "they will be informed" it says they will "see".
3. It does not matter if oil runs out in 100 years ( although I don't know why you believe this). When I was young they told us we would run out of oil by the year 2000. Did not believe it then, don't believe it now. What matters is the existence of cheap energy fostered industrialization which literally brought about the conditions where it makes sense to talk about whole nations "seeing" the dead bodies of the witnesses so the passage does not have to be spiritualized anymore.
4. It matters little to the argument whether it was mostly because of dinosaurs or because of biomass - it makes a difference that organic fuels were present.

I really consider this quite a foolish argument - I mean my only point was that Steve should not have ridiculed the idea or considered it silly.

I am really glad that those worthless arguments you presented were off the top of your head. You can be excused for making irrelevant statements. It would be a real shame if those were your arguments after much though and study.

Please do not respond as we have already given this distraction more words than it deserves. I just couldn't let your ignorance sit there without a response.

kakapo said...

That's excellent. "Dinosaurs did not lead to petroleum" is irrelevant to the claim that "God produced dinosaurs to give us oil". That has to go down as one of the best claims I've ever read.

You also really need to do a lot more study of Revelation before you assert "prophecy" has only one interpretation - there are at least 4 major interpretations of the work as prophecy. The reason that the dispensational premillenial interpretation of the whole book (your passage is just one tiny part) was not accepted within the church is that there are significant consistency and hermeneutical problems with it.

Don't worry though, past experience has taught me that discussion with someone who is both ignorant and ignorant of his ignorance is not beneficial to anyone.

John Hansen said...

kakapo -
So I am curious. Are you really interested in communication or are you so absorbed in your own self image that you do not really want to communicate clearly with an adversary. Look at the problems with your last post.

1. "God produced dinosaurs to give us oil" is just a short hand simplification of what Rana originally proposed. Many times an idea becomes associated with a simple way of putting it. Careful people do not pettifog over the 'shorthand'. If I have been guilty of this, I am sorry. You seem to revel in the opportunities it gives to claim the stupidity of your adversary.

The whole proposition was originally taken from a context of a discussion about how to reconcile all of the past life on earth with the design of God for man. I am not speaking from looking at Rana's original text, just from my memory of reading his books. The point, if I am remembering correctly, was that there could be good reason for God to allow a great deal of animal death prior to the fall if you assumed that part of the command to "subdue the earth" in Genesis included man's industrial progress as God ordained. So the fact is that whether it was "dinosaurs" or just "biomass" is truly irrelevant to the original point. You could have seen this if you had given it some thought. You would not see it if your object was to ridicule.

The suggestion that man's industrial progress satisfies a problem with Revelation that would have been unthinkable in John's day ( I hope you accept John as the author of Revelation ) is of my own doing.

Now read over all of our discussion. Yes my viewpoint is consistent with a premillennial ( correctly spelled for you ) viewpoint, but all I was stating was that it makes sense with a certain interpretation of the text. I was not asserting that my interpretation had to be correct.

The whole exercise was to illustrate that there are plausible ways to think of these things and that Steve's dismissal of them as "silly" is unfounded, unless he is constrained by his world view. In other words, his confirmation bias leads to dismissal of others.

In all the discussions I have had with you on this board I find you quick to dismiss your opponents as stupid. The reason I typed what I typed has more to do with answering your points ( all of which I did not consider very relevant to the original argument ) than to try and do some careful analysis. The whole thing is about a side issue anyways.

You know maybe if we both back down a little from using the word "ignorant" to describe each other, we might actually end up having some useful dialogue. You obviously have done some study ( even if you fail to spell millennial right ) ( I had to look it up when spell checker flagged it ). I apologize for calling you ignorant. What I meant is that I felt your points were irrelevant to the discussion. Please accept my apology.

Interested in a reply if you are so inclined.

Jason said...

Here is a nice fairly recent article in the NY Times regarding the origin pf oil. http://www.nytimes.com/2010/08/03/science/03oil.html