Yes, Virginia, there is Junk DNA

[John_Harshman]

@PDPrice

What I don’t see is you citing anything that shows I’m wrong.

Again, you should look at the Ohno paper that was the original mention of “junk DNA”. You will find that Ohno doesn’t equate junk DNA with non-coding DNA, despite the claims in your lawyer’s letter.

@PDPrice

You are arguing there is no function based upon your lack of knowledge about what the function could be.

This sort of gross misunderstanding is why I posit that you don’t even read what I write. Lack of knowledge is not one of the arguments.

@PDPrice

Why do you say that?

I’m puzzled. Isn’t this what you say yourself? Mutations that degrade function are much more common than mutations that improve function.

@PDPrice

So you’re saying, in essence, if most of the genome is not junk, Dr Sanford would be completely correct. Do I understand you so far?

Not quite. If Sanford were correct about genetic entropy, the consequences would be different from what he thinks.

@PDPrice

Such populations have much lower per-generation germline mutation rates, by virtue of the fact that there is less time for mutations to accumulate.

Not true. Mutations occur mostly during DNA replication. The number of germline generations between individual generations doesn’t vary all that much in metazoans. Of course it depends on how many eggs and sperm are produced, and there are in general more mutations in sperm than in eggs. Mutation rate is actually somewhat negatively correlated with generation time. And such species do not have much lower percentages of noncoding DNA; that varies all over the map. Nor have you shown that functional non-coding DNA is more likely to be evolving nearly neutrally.

[RonSewell (RonS)]

@PDPrice

You would need to back up your claim that the term ‘Junk DNA’ has never meant the entirety of the noncoding region.

So are you saying that even the regulatory areas of the genome were referenced as junk? How were genes thought to be expressed?

The following from The Case for Junk DNA - this paper provides an accessible discussion of the state of the Junk DNA debate:

Although the term ‘‘junk DNA’’ was already in use as early as the 1960s, the term’s origin is usually attributed to Susumu Ohno. As Ohno pointed out, gene duplication can alleviate the constraint imposed by natural selection on changes to important gene regions by allowing one copy to maintain the original function as the other undergoes mutation. Rarely, these mutations will turn out to be beneficial, and a new gene may arise (‘‘neofunctionalization’’). Most of the time, however, one copy sustains a mutation that eliminates its ability to encode a functional protein, turning it into a pseudogene. These sequences are what Ohno initially referred to as ‘‘junk’’ although the term was quickly extended to include many types of noncoding DNA. Today, ‘‘junk DNA’’ is often used in the broad sense of referring to any DNA
sequence that does not play a functional role in development, physiology, or some other organism-level capacity. This broader sense of the term is at the centre of most current debate about the quantity—or even the existence—of ‘‘junk DNA’’ in the genomes of humans and other organisms.

It has now become something of a cliche´ to begin both media stories and journal articles with the simplistic claim that most or all noncoding DNA was ‘‘long dismissed as useless junk.’’ The implication, of course, is that current research is revealing function in much of the supposed junk that was unwisely
ignored as biologically uninteresting by past investigators. Yet, it is simply not true that potential functions for noncoding DNA were ignored until recently.

[glipsnort (Steve Schaffner)]

@PDPrice

That is called genetic entropy. It’s exactly what Dr Sanford is arguing is happening. So you’re saying, in essence, if most of the genome is not junk, Dr Sanford would be completely correct. Do I understand you so far?

You’ve misunderstood both the mutational load argument and Sanford. Sanford’s genetic entropy posits that there is a large class of mutations that are so slightly deleterious that natural selection can’t weed them out. That claim is independent of how much of the genome is functional. There’s no reason at all to believe it’s true, again independent of the existence of junk DNA.

[Timothy_Horton]

@PDPrice

That is called genetic entropy. It’s exactly what Dr Sanford is arguing is happening. So you’re saying, in essence, if most of the genome is not junk, Dr Sanford would be completely correct. Do I understand you so far?

Sanford is a YEC. His genetic entropy concept is based on the claim all genomes were created “perfect” only 6000 years ago and have been degrading ever since. For his evidence he listed the decreasing ages of the Biblical patriarchs. His entire concept of genetic entropy has been thoroughly debunked and rejected by the scientific community. Do you really want to use him as support for your argument?

[PDPrice (Paul Price)]

@John_Harshman

Again, you should look at the Ohno paper that was the original mention of “junk DNA”. You will find that Ohno doesn’t equate junk DNA with non-coding DNA, despite the claims in your lawyer’s letter.

I just read it. It does equate non-coding DNA with ‘junk’, just as my citation said. He implies that everything outside of the DNA which “codes for genes” must be junk.

I also cited:

According to T. Ryan Gregory, the nature of junk DNA was first discussed explicitly in 1972 by a genomic biologist, David Comings, who applied the term to all non-coding DNA.[39] [from Wikipedia]

What is your reason for dismissing this citation?

@John_Harshman

This sort of gross misunderstanding is why I posit that you don’t even read what I write. Lack of knowledge is not one of the arguments.

You asked me how much of the genome had been experimentally proven to have a function. Behind that question is the implicit premise that if it hasn’t been proven functional, it must be assumed to be junk. Right? Otherwise, why would you ask? Do you agree if that if a function has not been proved experimentally, it can be assumed to have no function?

@John_Harshman

I’m puzzled. Isn’t this what you say yourself? Mutations that degrade function are much more common than mutations that improve function.

Oh yes, that is certainly the case, but I can never take it for granted that somebody is going to acknowledge that fact. Thank you for acknowledging it. Why would you say it is the case that degrading mutations are so much more common? Why, for example, wouldn’t we expect beneficial mutations to be more common than deleterious ones?

@John_Harshman

Not quite. If Sanford were correct about genetic entropy, the consequences would be different from what he thinks.

Perhaps you disagree with Sanford’s assessment of how GE would play out in the real world over time, but you do seem to agree with him that mutational meltdown would be inevitable, assuming that a sizable percentage (much greater than 10%) of the genome were indeed functional. Is that correct?

@John_Harshman

Not true. Mutations occur mostly during DNA replication. The number of germline generations between individual generations doesn’t vary all that much in metazoans.

What do you mean by “all that much”? I know I’ve been asked about mice before, and mice do indeed have a lower per-generation mutation rate than humans.

@John_Harshman

And such species do not have much lower percentages of noncoding DNA

I’ve read many sources saying otherwise, such as (just one example)

An Ancient Protein Balances Gene Activity And Silences Foreign DNA In Bacteria

Yes, here’s another Wikipedia quote just for ease:

The main reason for the relative density of bacterial genomes compared to eukaryotic genomes (especially multicellular eukaryotes) is the presence of noncoding DNA in the form of intergenic regions and introns.[10]

@John_Harshman

Nor have you shown that functional non-coding DNA is more likely to be evolving nearly neutrally.

According to what I’ve read, it is indeed believed that noncoding DNA has a higher fraction of nearly (effectively) neutral mutations compared to coding regions:

“…as much as 95% and as little
as 50% of mutations in non-coding DNA are effectively
neutral; therefore, correspondingly, as little as 5% and as
much as 50% of mutations are deleterious.”

Eyre-Walker, A., and Keightley P.D., The distribution of fitness effects of new mutations, Nat. Rev. Genet. 8(8):610–8, 2007.
The distribution of fitness effects of new mutations | Nature Reviews Genetics.

Now, once again, where exactly are you arriving at your figure of 90% junk? Based upon what can you claim to actually know that only 10% of our DNA has any function?

[T.j_Runyon]

@PDPrice

I just read it. It does equate non-coding DNA with ‘junk’, just as my citation said. He implies that everything outside of the DNA which “codes for genes” must be junk.

Then you are misunderstanding it. Junk is non-coding. But not all non-coding is junk. I don’t know how you can read that paper and not come to the conclusion that’s what he said.

Edit: @PDPrice you really need to read the paper @RonSewell links to above. It will clear up your misconceptions. Even cites the Comings paper you just mentioned.

[John_Harshman]

@PDPrice

I just read it. It does equate non-coding DNA with ‘junk’, just as my citation said. He implies that everything outside of the DNA which “codes for genes” must be junk.

He says no such thing. Note that he included several sorts of non-coding DNA within the fraction that he called genes, specifically promoters and operators. You have made the additional conflation of “gene” with “protein-coding”, which Ohno didn’t do. He also mentions spacer regions and ribosomal RNAs, all functional and non-coding. You are confused.

@PDPrice

What is your reason for dismissing this citation?

Did you look to see what Gregory, and before him Comings, actually said?

@PDPrice

Behind that question is the implicit premise that if it hasn’t been proven functional, it must be assumed to be junk. Right?

Wrong. I ask because you made a positive assertion, that most of the genome has been found to be functional.

@PDPrice

Do you agree if that if a function has not been proved experimentally, it can be assumed to have no function?

No. What I say is that there is good evidence that most of the human genome is not functional. This is not an assumption but a conclusion from evidence.

@PDPrice

Why, for example, wouldn’t we expect beneficial mutations to be more common than deleterious ones?

Because functional sequences are for the most part already well-adapted for their current functions. Purifying selection is therefore the most common sort. Sequences currently under positive selection are not common, and would generally result from a change in selective regime.

@PDPrice

you do seem to agree with him that mutational meltdown would be inevitable, assuming that a sizable percentage (much greater than 10%) of the genome were indeed functional. Is that correct?

There is actually some argument about whether this is true, but that is in fact the mutational load argument.

@PDPrice

What do you mean by “all that much”?

I mean that it doesn’t vary nearly as much as generation time does. Despite a lower per-generation mutation rate (which is in fact a bit puzzling to me), the per-year mutation rate is much higher in Mus musculus than in Homo sapiens. So mice should have deteriorated at a much higher rate than humans and should be extinct by now.

@PDPrice

I’ve read many sources saying otherwise

Bacteria are different. Most of them have very small genomes with almost no junk DNA. Apparently, their very high reproduction rate makes the cost of replication a much greater selective force than in eukaryotes. We haven’t been talking about bacteria, though if you had read you would have seen that I mentioned that they have little junk.

@PDPrice

According to what I’ve read, it is indeed believed that noncoding DNA has a higher fraction of nearly (effectively) neutral mutations compared to coding regions

Sorry, but you are still confusing “non-coding” with “junk”. That was a comparison of coding regions with non-coding regions in general, not with functional non-coding regions.

@PDPrice

Based upon what can you claim to actually know that only 10% of our DNA has any function?

This is the nth time you have ignored the arguments for junk DNA and asked for the evidence you have already been told about.

[Rumraket (Mikkel R.)]

@PDPrice

Now, once again, where exactly are you arriving at your figure of 90% junk? Based upon what can you claim to actually know that only 10% of our DNA has any function?

Read the papers referenced in the link I gave in my first post in this thread.
The evidence for junk comes from multiple independent categories of evidence. In no particular order, they are:
A) Understanding biochemistry and looking at how functional genes work(and what causes them not to), and seeing that much of our DNA looks like things that used to be functional really long ago, but accumulated exactly the types of mutations that make functional things stop functioning(frameshift mutations, premature stop codons, lack of functional promoters, deletion of exons, and innumerable other examples).
B) Interspecies genome-size comparisons, aka the C-value paradox.
C) Conservation.
D) Calculations of genetic load.
E) The mutual corroboration of these different lines of evidence, as in the things that look like broken versions are also generally much less conserved, and contribute the most to excess genome size (such as broken transposons, of which >40% of your genome appears to consist).

To truly understand each of these arguments, I have merely mentioned them here, not really explained them in any appreciable detail, you need to read the papers.

[PDPrice (Paul Price)]

@John_Harshman

He also mentions spacer regions and ribosomal RNAs, all functional and non-coding. You are confused.

Yes, that’s fine, and I can accept this as a more precise answer. But it also appears to be a nitpick, rather than something substantially different from what I originally said (that the term ‘junk DNA’ was being applied to the whole non-coding region). There are some exceptions that are ‘noncoding’ and ‘non-junk’, but those are exceptions to the generalization that non-coding = junk. And moving on to my next citation:

@John_Harshman

Did you look to see what Gregory, and before him Comings, actually said?

You’re asking me a question without first answering the one I asked you. Why are you dismissing this citation as inaccurate? If it’s inaccurate, then so be it. Maybe somebody can even make an edit to the wikipedia page to reflect that.

@John_Harshman

Wrong. I ask because you made a positive assertion, that most of the genome has been found to be functional.

Did I? I recall saying that the opposite claim has been shown wrong (by things such as ENCODE, for example). I don’t recall making the claim that most of the genome has been directly, experimentally shown to have a function. I think there’s still a lot to learn in this area.

@John_Harshman

What I say is that there is good evidence that most of the human genome is not functional. This is not an assumption but a conclusion from evidence.

Much of this evidence seems to be “it cannot be functional, or evolution would be impossible”, which is circular. Your mutation load argument being a case in point there.

@John_Harshman

Because functional sequences are for the most part already well-adapted for their current functions.

The mutations are independent of the sequences they’re acting on (otherwise we’re talking about guided evolution / intelligent design, not unguided). Meaning, your above statement is not really an answer to my question of why we would not expect most mutations to be beneficial. Just because something is “well-adapted” doesn’t mean it’s impossible to add new information and new functions, right? Otherwise, we could never get from well-adapted bacterium all the way up to well-adapted human.

@John_Harshman

There is actually some argument about whether this is true, but that is in fact the mutational load argument.

Let’s not beat around the bush. You just put forward the mutational load argument yourself. Do you not stand behind it as a valid argument? You seem to be agreeing with Sanford’s conclusion that mutational load is a problem (or would be), but then using Junk DNA as a rebuttal, since most of the mutations must be of no effect if they land in this useless region. But the citations I’ve provided you actually call these mutations effectively neutral, not strictly neutral. In fact, the population genetics experts I’ve cited have explicitly said that essentially no mutations are of no effect, which is in stark contrast to your claims.

@John_Harshman

So mice should have deteriorated at a much higher rate than humans and should be extinct by now.

Don’t you think mice have a lot more purifying selection going on compared with human beings?

@John_Harshman

We haven’t been talking about bacteria, though if you had read you would have seen that I mentioned that they have little junk.

You actually said, “there wouldn’t be a mouse, fly or paramecium left in the world.” In any case, little junk [correction, noncoding DNA] means fewer nearly neutral mutations, which means more effective purifying selection, which in turn means less of a problem with genetic entropy.

@John_Harshman

This is the nth time you have ignored the arguments for junk DNA and asked for the evidence you have already been told about.

Can you cite a source promoting your 90% junk claim, just so I can know what you’re drawing from? I am still not sure what you’re talking about. I’m in this discussion with you, not with other people posting here. I am keeping it focused.

[Rumraket (Mikkel R.)]

@PDPrice

Yes, that’s fine, and I can accept this as a more precise answer. But it also appears to be a nitpick, rather than something substantially different from what I originally said (that the term ‘junk DNA’ was being applied to the whole non-coding region).

No, that’s exactly why you’re wrong. You can’t just declare that the reason why you’re wrong is a “nitpick” and the pretend you’ve rebutted the argument.

@PDPrice

There are some exceptions that are ‘noncoding’ and ‘non-junk’, but those are exceptions to the generalization that non-coding = junk.

But then you’re the one making the generalization, not Ohno.

[Rumraket (Mikkel R.)]

@PDPrice

I’m in this discussion with you, not with other people posting here.

Why? They are giving you what you are asking for. Why must what you are asking for be present in a rectangular space of your browser window with the name John Harshman at the top of it, when it is what you are asking for?

@PDPrice

I am keeping it focused.

The responses you are getting from other people are in fact on topic, so you’re not “keeping it focused”, you’re wasting time distracting from and ignoring relevant evidence and arguments.

[John_Harshman]

@PDPrice

But it also appears to be a nitpick, rather than something substantially different from what I originally said

That only means you don’t understand the difference. The point is that junk DNA is a subset of non-coding DNA. It doesn’t matter whether junk is a small or large fraction of non-coding DNA; they are not synonymous, and are not defined that way. In the human genome, most non-coding DNA is junk. The part that’s functional brings the fraction of functional DNA from 2% (protein-coding) to 10%.

@PDPrice

You’re asking me a question without first answering the one I asked you.

Considering that you almost never answer my questions, this doesn’t seem like a good point for you. I’ve never looked at Comings, but I know what Gregory thinks junk DNA is. Wikipedia repeats a common misconception; that’s hardly the first time.

@PDPrice

I recall saying that the opposite claim has been shown wrong (by things such as ENCODE, for example).

ENCODE, at one point, claimed that 80% of the genome had been shown to be functional, and suggested that further work would change that to 100%. But they’ve walked that way back since. Further, the definition of function used in that first paper is bogus, as random sequences would generally show function baed on their methods. No hope for you from that direction. What evidence can you produce to contradict the claim that most of the genome is junk?

@PDPrice

Much of this evidence seems to be “it cannot be functional, or evolution would be impossible”

No, none of the evidence says any such thing. More evidence that you don’t read for comprehension: you consistently fail at attempts to paraphrase my arguments.

@PDPrice

Just because something is “well-adapted” doesn’t mean it’s impossible to add new information and new functions, right?

No, but it does mean that it’s unlikely. As creationists often say, there are more ways to break something than to improve it. Nor does “unlikely” mean “impossible”. The great thing about natural selection is that it preserves and amplifies beneficial mutations while eliminating deterious ones. The prior distribution is quite unlike the posterior distribution.

@PDPrice

You just put forward the mutational load argument yourself. Do you not stand behind it as a valid argument?

It’s valid if the model of evolution on which it’s based is correct. There’s some controversy about that. As I’ve said before, it’s the least of the arguments for junk. But you have ignored all the others, for some reason.

@PDPrice

But the citations I’ve provided you actually call these mutations effectively neutral, not strictly neutral. In fact, the population genetics experts I’ve cited have explicitly said that essentially no mutations are of no effect , which is in stark contrast to your claims.

That’s one citation, and the authors’ opinion that there are no strictly neutral mutations is an unreferenced, unsupported opinion tossed off in the introduction. The rest of the paper shows that there is no way to distinguish nearly-neutral from strictly neutral mutations.

[John_Harshman]

@PDPrice

Don’t you think mice have a lot more purifying selection going on compared with human beings?

Of course they do; more frequent generations and a higher population size. But that would also require lots more excess reproduction than is observed if they didn’t have junk DNA.

@PDPrice

You actually said, “there wouldn’t be a mouse, fly or paramecium left in the world.”

Which of these, in your estimation, are bacteria? I can’t make any sense of your statement unless you somehow think that at least one of them is.

@PDPrice

Can you cite a source promoting your 90% junk claim, just so I can know what you’re drawing from?

I have made the arguments, which you have ignored. Some others have made the same arguments at somewhat greater length, which you have ignored. I have directed you to links provided by others, which you have ignored. And I can’t see why this discussion needs to be private. The fact that you ignore most of what I post gives me no reason to go into greater detail.

[PDPrice (Paul Price)]

@John_Harshman

I have directed you to links provided by others, which you have ignored.

I asked you to provide me one citation for your claim, but for some reason you keep dodging and refusing to simply do that. I didn’t ask “others”, I asked you. Nobody’s forcing you to respond, but by continually refusing to back up your assertions you appear to be less than genuine.

So far you haven’t quoted anything, and you haven’t cited anything. You’ve claimed my citations are wrong, but you haven’t actually substantiated any of those claims (with the exception of the aforementioned minor clarification regarding Ohno’s paper–which I also provided). Thanks for your time, but I’ll be going now. I’m not going to just keep repeating the same questions to have you keep dodging them or expecting others to do your heavy lifting for you.

[PDPrice (Paul Price)]

@John_Harshman

That’s one citation, and the authors’ opinion that there are no strictly neutral mutations is an unreferenced, unsupported opinion tossed off in the introduction.

That’s one more expert citation than you’ve provided.

[Rumraket (Mikkel R.)]

@PDPrice

I asked you to provide me one citation for your claim, but for some reason you keep dodging and refusing to simply do that.

When he says others have given links to what you’re asking for, and that this is demonstrably correct, he’s not dodging. You are.

[PDPrice (Paul Price)]

@John_Harshman

I’ve never looked at Comings, but I know what Gregory thinks junk DNA is. Wikipedia repeats a common misconception; that’s hardly the first time.

The Wikipedia is citation is about Comings, not Gregory. If you haven’t ever looked into it, then that means you cannot claim it’s a misconception. You’re just dismissing the citation out of hand because it doesn’t fit the narrative you’re siding with. You want me to play a rigged game, and I am not going to continue doing so.

[T.j_Runyon]

@PDPrice

The Wikipedia is citation is about Comings, not Gregory. If you haven’t ever looked into it, then that means you cannot claim it’s a misconception. You’re just dismissing the citation out of hand because it doesn’t fit the narrative you’re siding with. You want me to play a rigged game, and I am not going to continue doing so.

It’s about Gregory talking about Comings. You will see Gregory mention Ohno’s definition (same one @John_Harshman has mentioned) and then mention that later on Comings applied it to all non-coding DNA.

[John_Harshman]

@PDPrice

The Wikipedia is citation is about Comings, not Gregory.

It’s about what Gregory said about Comings. I have access to neither publication.

I don’t know if anyone else has ever put this up here, but this will tell you what Gregory thinks about junk DNA.

[RonSewell (RonS)]

@PDPrice

To quote once again from the Wikipedia page,

According to T. Ryan Gregory, the nature of junk DNA was first discussed explicitly in 1972 by a genomic biologist, David Comings, who applied the term to all non-coding DNA.[39]

Umm… T. Ryan Gregory is the coauthor of the paper I linked earlier, “The Case for Junk DNA”, definitely pro junk. Without access to the original referenced Comings paper, it is difficult to construe exactly what he said.

@PDPrice

The Wikipedia is citation is about Comings, not Gregory. If you haven’t ever looked into it, then that means you cannot claim it’s a misconception.

Do you have a copy of the original cited Gregory?