Pete's Quite Thread post

[Tomk80]

Let me respond to this as if it encompassed everyone's objection.

First, let me agree to some facts:
Can mutations cause indels? yes.
Can mutations cause large indels? yes.

Mutations do not cause indels. Indels are a form of a mutation.

For the sake of discussion, let's ignore the non-indels (as they represent far fewer nt, but far more events, this shouldn't be a problem for anyone).

What do you consider non-indels when referring to the paper?

So, for the sake of discussion, the accumulation of indels represents the difference between a non-human ancestor and human-kind. Clearly, they did not all happen at once. However, just as clearly, these indels are characterized NOT by simple repetition of existing genetic material (if they were, this would be observed in the alignment process, incidentally).

How do you conclude from the data that the accumulation of indels represents the difference between a non-human ancestor and human-kind? We know virtually nothing about the indels we are talking about, other than that they are there. We don't know whether they are coding for anything, we don't know in what kind of DNA region they are. So how do you conclude this? They might all be located in stretches of non-coding DNA for all we know from the paper? So where do you get the conclusion that they represent the difference between a non-human ancestor and human-kind. You're putting the cart before the horse here.

But in the case under discussion we were NOT talking about some random 4000nt insertion or some 4000nt replication. We were talking about 4000nt hunks of NEW CODE. 4000nt that, for all we know, is critical, in its entirety, to construct the creature we know as "man". As Gluadys quotes Dawkins, "Jumping gaps is not what evolution [by which we can probably agree that Dawkins means natural selection] does." 4knt hunks of new code are most certainly gaps. To blythely wave our hand at such an insertion and say "it is just a mutation" is preposterous. As Gluadys correctly says:

Since a mutation is a change in the DNA, and an insertion changes the DNA, an insertion is necessarily a mutation. I really don't get how you can conclude that this would not be the case.

But on to the rest of your post. How do you know it is 'new code'? What is 'new code' according to you, and how does it seperate itself from 'old code'? What do we know of these mutations that leads you to this conclusion? Why can't it be a replication, to name an example? A number of the indels in the paper were already identified as being caused by slippage, especially in the homopolymeric regions. Furthermore, inversion and translocation were also pointed out as mechanisms. Next to that, the 10,000 bases substitution I referred to in the paper on genetic diseases isn't a duplication either. You are making a lot of assertions here, but I have no idea where you get them all from.

 

[jnhofzinser]

Let's consider the probability of an "interesting" 1000nt insertion:

For sake of discussion, let's let the probability of a beneficial (point) mutation be p, the probability of a neutral (point) mutation be x, and that of a deleterious (point) mutation be d. The probability of a (point) mutation is m=p+x+d. Now let's consider random insertions (these are the kind that are interesting -- duplications of hunks of DNA are not interesting).

Also for the sake of discussion, let's imagine that the probability of a single-nt insertion i1 is equal to m. (any clues as to whether this is optimistic or pessimistic?). The probability of a beneficial single-nt insertion is then also b1=p.

Now, the probability of a double-nt insertion (i2) is certainly less than i1=m. Let's let i2=q2*m, q2<1. The probability of a double-nt beneficial insertion is now b2=q2*p*(p+x)/m (that is to say, one of the two nt need not be beneficial, but it must not be deleterious).

Similarly, the probability of a triple-nt insertion is i3=q3*m, q3<q2, and b3=q3*p*[(p+x)/m]^2

The probability of a beneficial 1000-nt insertion is b1000u=q1000u*p*[(p+x)/m]^999 (letting q1000u denote the chance that an insertion is at least 1000 nt in length). Note the "u" -- this indicates that this probability is an upper-bound number for the phenomenon of interest. This is the number for any 1000-or-greater-nt insertion, including those that have only the selective advantage of a point mutation. The lower-bound (also unrealistic, I appreciate) is b1000l=q1000u*p*(p/m)^999.

So let's plug in some numbers. With optimism, let's let only 10% of all (point) mutations be deleterious. This means that b1000u=q1000u*p*2e-46, with p<<1 (according to Pete, p=2.56e-6, for example), and q1000u<<1 as well. Nominally, we have a (very?) optimistic upper bound of b1000u=1e-50.

If you follow the math, you can appreciate why I might say that treating such an insertion as a single mutation (i.e., b1000~b1) is "preposterous" or a "leap of faith".

Now let's keep in mind: Britten, looking at just a small fraction of the human genome catalogues no less than six insertion events of 1000nt or greater. It is likely that there are hundreds of such events in the entire genome. The chance of just one such mutation happening in 10 million years with a stable population of 100,000 (Pete's numbers) is (as an optimistic upper bound, mind you) 5e-40.

So are insertion mutations a problem for the traditional natural selection+mutation kind of evolution? Based on limited and conservative data, the answer is an unequivocal, resounding YES

 

[jnhofzinser]

You are putting the cart before the horse

Dude -- those indels represent the majority of the ONLY observable genetic differences between humans and chimpanzees. If they don't account for what it is to be human, then what, pray tell, does?

 

[Manic Depressive Mouse]

The issue is a single common ancestor, its absured.

Because it contradicts your beliefs, not because of the evidence or the logistics of it. Unless you would like to be more specific and tell us exactly what part of the ToE is absurd?

Yes, of course I know, thus my interest in evolutionary biology.

So one second you're arguing that natural selection has been presumed at too high a level (common ancestor), the next you're arguing that it needs to have happened at a higher level for your beliefs to be true.

You do notice the confliction, right? This is the reason nobody takes you seriously, you'll argue anything so long as it supports your beliefs even if it means contradicting yourself let alone the facts.

Read the introduction to Darwin's Orign of Species.

Ahh yes, we get back to your Feudian fixation with Darwin. I'm sorry but Darwin knew next to nothing about evolution, and anything he says on the subject is not considered by anyone, bar yourself, the be-all and end-all of the ToE.

Creationism is one long argument againt Darwinism, make no mistake, it's in the literature if you read it.

Except the parts where they need hyper-darwinism to make their flood model work, right?

Of course we are critical of forensics and archeology, we are examining the evidence for history, we have to be critical.

So do you believe that forensics should be left to theology as well? You don't seem very critical of the Bible as historical evidence either. Funny that.

You didn't understand the literature obviously or you would have quoted it.

Mark if anyone's understanding of biology has been shown to be severly lacking on this forum's it's yours, not mine. Which is another reason why nobody takes you seriously, the number of basic errors you've made (and claim as fact) are momentous. For example the time you claimed that the difference between warm blooded and clood blooded animals, genetically, was to great for evolution to happen.

Yea, the minority that did the most to preserve and mold western civilization.

Right wing Biblical fundamentalists? One of the main aspects of western civilization is liberty, something they actively opposed with slavery.

As long as they argue against the most basic premise of Christian theism 'In the begining God', I'll keep coming back, and I am not alone.

Who argues that? Certainly not scientists. They deal with how the universe formed, not who did it and why.

I presume nothing except the agency of God in creation. The Bible as history has no equal, the Scriptures have stood the test of every psuedo-scientific argument against it. You have nothing but anecdotal evidence and pedantic satire to support your worldview and btw, the Bible does not teach that the world is flat, that is absurd.

What shape is a circle, Mark? And it also says that the sun orbits the earth, as God moved the sun to change the time of day on two occasions in the OT.

The Scriptures are a history of the spiritual retribution of man, not the natural history of the world. As natural history sources they have been shown to be conclusively false. Why do you think most people accept that the world was not created word for word as in the Bible? Because that's wrong?

Do you even know the deffinition of science, Mark? Because the only thing that qualifys as "pseudo-science" in the Crevo debate is creation science and ID. Look up a dictionary, check it out.

There would be no such thing as modern science had it not been for the Protestant Reformation. Your ignorance of history is rivaled only by your substitution of satire for science.

Your arrogence is only rivaled by your ignorance. What do you do Mark? Because in case you havn't guessed I AM A SCIENTIST.

If I'm so ignorant of history Mark, would you kindly inform me of who the Reverand William Buckland was, and what his work in geology disproved?

I'm not going to comment on the immature and derrogatory handwaving in the rest of your post. You have made it clear time and time again you believe NS is a myth. If you will insist on ignoring all the evidence to the contrary at least have the common decency to stop claiming your belief as fact.

 

[jnhofzinser]

How do you know it is 'new code'?

It is certainly a stretch to suggest that what makes us uniquely human is 'old code', don't you think? But hey! "Biochemist" on iidb argues exactly that: he claims that all life was coded into the first single-cell creature by a creator. Is this what you are suggesting?

 

[Manic Depressive Mouse]

So Mark would you kindly tell us what mechanism prevents human speciation that is different from every other organism?

Could you also explain the other humans species we know exsited, such as:

Homo floresiensis

Homo habilis

Homo georgicus

Homo erectus

Homo ergaster

Homo antecessor

Homo sapiens (archaic) (also Homo heidelbergensis)

Homo sapiens neanderthalensis

Homo sapiens sapiens

 

[Tomk80]

It is certainly a stretch to suggest that what makes us uniquely human is 'old code', don't you think? But hey! "Biochemist" on iidb argues exactly that: he claims that all life was coded into the first single-cell creature by a creator. Is this what you are suggesting?

Nope. But most of the indels were in Alu repeats and homopolymeric sequences. In other words, these are either sequences that repeat themselves a number of times or sequences that consist of only one base. A duplication event in this leads to an increase in the chromosomal length, but would only consist of copied code. Is that what you mean with 'new code'. Another interesting indel was the result of a reversion insertion. So that is a part of the genetic code that is first reversed and then inserted in another part of the chromosome. Is that what you mean with 'new code'? Other indels can be caused by unequal crossing over. That means that in the recombination process the crossing over does not take place at the same place on the recombinating chromosomes. Is that what you mean with 'new code'?

Not all of the indels were described in the paper, but as of yet we have no reason to assume that processes like these can account for all of the insertions that are longer than a certain number of basepairs. That is your assertion, but it has no back-up from the paper in any way.

 

[Tomk80]

Dude -- those indels represent the majority of the ONLY observable genetic differences between humans and chimpanzees. If they don't account for what it is to be human, then what, pray tell, does?

But they do not represent the majority of the mutation events. There is a big difference there. Yes, they represent the majority of the difference in exact base pair sequence, but the difference in length in the base pair sequence is not the most important thing causing differences between organisms.

We don't know what the indels do that are described in the paper. For all we know, the majority might be in non-coding regions, in which case they will be completely neutral. They might be insertions in regulatory regions, in which case all they do is cause a difference in gene expression, not in which genes are expressed.

Personally, I think we have to search for most differences between apes and humans in differential gene expression. Ie, some genes are expressed more or less than others. Similar findings have been given in dogs and wolves, were the difference in brain structure is especially connected to differences in the expression of certain genes at certain points, not to differences within the genes. But we just don't know at this point. We do know that there is a disconnect between the number of mutations and the morphological differences, because a lot of mutations can be neutral or have effects that do not directly translate in different morphology. As we have no information on the precise location in the genomic sequence of the indels talked about here, we just cannot draw the conclusion from this paper that they are the cause of the difference between humans and chimpanzees. To do that, we will need more in depth knowledge on the location of the indels, whether they are in expressed regions and what the genes do that are affected by these indels. You are putting the cart before the horse by drawing such conclusions.

 

[Tomk80]

Let's consider the probability of an "interesting" 1000nt insertion:

For sake of discussion, let's let the probability of a beneficial (point) mutation be p, the probability of a neutral (point) mutation be x, and that of a deleterious (point) mutation be d. The probability of a (point) mutation is m=p+x+d. Now let's consider random insertions (these are the kind that are interesting -- duplications of hunks of DNA are not interesting).

Also for the sake of discussion, let's imagine that the probability of a single-nt insertion i1 is equal to m. (any clues as to whether this is optimistic or pessimistic?). The probability of a beneficial single-nt insertion is then also b1=p.

Now, the probability of a double-nt insertion (i2) is certainly less than i1=m. Let's let i2=q2*m, q2<1. The probability of a double-nt beneficial insertion is now b2=q2*p*(p+x)/m (that is to say, one of the two nt need not be beneficial, but it must not be deleterious).

Similarly, the probability of a triple-nt insertion is i3=q3*m, q3<q2, and b3=q3*p*[(p+x)/m]^2

The probability of a beneficial 1000-nt insertion is b1000u=q1000u*p*[(p+x)/m]^999 (letting q1000u denote the chance that an insertion is at least 1000 nt in length). Note the "u" -- this indicates that this probability is an upper-bound number for the phenomenon of interest. This is the number for any 1000-or-greater-nt insertion, including those that have only the selective advantage of a point mutation. The lower-bound (also unrealistic, I appreciate) is b1000l=q1000u*p*(p/m)^999.

So let's plug in some numbers. With optimism, let's let only 10% of all (point) mutations be deleterious. This means that b1000u=q1000u*p*2e-46, with p<<1 (according to Pete, p=2.56e-6, for example), and q1000u<<1 as well. Nominally, we have a (very?) optimistic upper bound of b1000u=1e-50.

If you follow the math, you can appreciate why I might say that treating such an insertion as a single mutation (i.e., b1000~b1) is "preposterous" or a "leap of faith".

Now let's keep in mind: Britten, looking at just a small fraction of the human genome catalogues no less than six insertion events of 1000nt or greater. It is likely that there are hundreds of such events in the entire genome. The chance of just one such mutation happening in 10 million years with a stable population of 100,000 (Pete's numbers) is (as an optimistic upper bound, mind you) 5e-40.

So are insertion mutations a problem for the traditional natural selection+mutation kind of evolution? Based on limited and conservative data, the answer is an unequivocal, resounding YES

In these calculations you are treating every new basepair inserted by an indel as a singular event. But from observations on genomic sequences, we know that a lot of insertions are copies, rearrangements etc. So an insertion of more than 1 nucleotide is often not a combination of singular events, but it is one event. This assumption you make does not add up with reality, hence your whole probability calculation becomes a moot point.

 

[jnhofzinser]

But they do not represent the majority of the mutation events.

If we do not know the mechanism that cause the indels:

Thus, no consistent single cause can be identified for even the longer indels, and several mechanisms must be responsible

then we cannot assume the standard assumption of event=indel holds. (I thought that this was obvious, but based on the responses I've got, it clearly needs to be said).

but the difference in length in the base pair sequence is not the most important thing causing differences between organisms.

Quite right. This is why I was only interested in the "interesting" indels -- i.e, the ones that did cause differences between organisms!

We don't know what the indels do that are described in the paper.

Fair enough.

But we just don't know at this point.

Fair, too.

we just cannot draw the conclusion from this paper that they are the cause of the difference between humans and chimpanzees.

Also true, which is why I always said "for purposes of discussion" -- it was not an assertion. Nor was it a "conclusion" as you repeatedly claim.

 

[jnhofzinser]

In these calculations you are treating every new basepair inserted by an indel as a singular event.

False. I am treating every new basepair as a component of a single event.

But from observations on genomic sequences, we know that a lot of insertions are copies, rearrangements etc. So an insertion of more than 1 nucleotide is often not a combination of singular events, but it is one event.

Yes, but those aren't particularly "interesting" -- that is, not many would claim that those represent the differences between organisms

This assumption you make does not add up with reality, hence your whole probability calculation becomes a moot point.

The "interesting" insertions are the information-rich ones. These are the ones (if any) that represent differences between organisms. Are you saying that these do not exist? Are you saying that just because researchers can account for simple insertions that only simple insertions are "real" -- i.e., until researchers can explain each genomic phenomenon, we don't have to consider it as part of our reality?

 

[jnhofzinser]

How about a status check -- let me know if I am close...

What I've called "interesting" indels are so very unlikely via mutation that:
- you think they don't exist (you assume that mutation is the default/only? mechanism)
- I think that they must arise via some as-yet-unknown-mechanism (I assume they do exist)

Fair?

The good news is that genomic research will eventually determine whether significant difference-critical insertions exist. Then we'll know. I'll gladly change my mind when the evidence calls for it.

 

[mikeynov]

How about a status check -- let me know if I am close...

What I've called "interesting" indels are so very unlikely via mutation that:
- you think they don't exist (you assume that mutation is the default/only? mechanism)
- I think that they must arise via some as-yet-unknown-mechanism (I assume they do exist)

Fair?

The good news is that genomic research will eventually determine whether significant difference-critical insertions exist. Then we'll know. I'll gladly change my mind when the evidence calls for it.

Not to re-point out the obvious, but indels (insertions/deletions) ARE mutations. So asking whether mutations caused indels is like asking whether the distortion of space/time by some mass caused gravity.

 

[jnhofzinser]

indels (insertions/deletions) ARE mutations.

Since you haven't been following, let me reiterate:

If there exists one significant insertion that is "information-rich" in the sense that it contributes to the difference between organisms, then the probability of this occurring as a single mutation in the available time is very small. If such an insertion exists, it would be one of those "big jumps" that Dawkins says don't happen. My claim has been all along (but I admit that I haven't been very clear, since I didn't appreciate the source of the misunderstanding) that Pete wasn't playing fair when he treats the probability of these events occurring as the same as any other mutation. They are not. All mutations are not created equal!

 

[Tomk80]

If we do not know the mechanism that cause the indels:

Thus, no consistent single cause can be identified for even the longer indels, and several mechanisms must be responsible

then we cannot assume the standard assumption of event=indel holds. (I thought that this was obvious, but based on the responses I've got, it clearly needs to be said).

But that is not what Britten concludes. There are several mechanisms causing indels, and Britten tells us in his conclusions that not one of those mechanisms but a multitude of those mechanisms are responsible. Meaning that for one indel, one mechanism is repsonsible and for another indel another mechanism. That is what he is saying. Nowhere does he state that they cannot be mutations, and nowhere is that conclusion as of yet justified.

Quite right. This is why I was only interested in the "interesting" indels -- i.e, the ones that did cause differences between organisms!

But nowhere is it stated that particular indels did or did not cause differences between organisms. The interesting indels are only interesting because of their length, we know nothing about their function. Even the long indels could be neutral, we just don't know.

Fair enough. Fair, too. Also true, which is why I always said "for purposes of discussion" -- it was not an assertion. Nor was it a "conclusion" as you repeatedly claim.

Fair enough, that was what you seemed to state to me.

 

[Tomk80]

False. I am treating every new basepair as a component of a single event.

The problem is that you are treating the insertion sections as if each base pair in that section is completely unrelated to the other. But especially with the larger insertions, we have no reason to think that this is the case.

Yes, but those aren't particularly "interesting" -- that is, not many would claim that those represent the differences between organisms

Nonsense. We do not know what caused the specific differences between the organisms. We do know that in the divergence insertions have occurred. And we know that insertions and deletions can affect large regions of the genome in one go. Whether they were or weren't responsible for the difference between the organisms isn't even relevant in discussion of the paper.

The "interesting" insertions are the information-rich ones. These are the ones (if any) that represent differences between organisms. Are you saying that these do not exist?

No, I am saying that we know mechanisms that can be responsible for such insertions and that we cannot conclude from the paper that these mechanisms were not responsible for the differences we see.

Are you saying that just because researchers can account for simple insertions that only simple insertions are "real" -- i.e., until researchers can explain each genomic phenomenon, we don't have to consider it as part of our reality?

Nope, I'm saying that we see quite complex insertions in nature of large pieces of genome. I am stating that we have observed the insertion of large pieces of genome due to natural mechanisms, and I've stated some of these mechanisms more than once now.

 

[Tomk80]

How about a status check -- let me know if I am close...

What I've called "interesting" indels are so very unlikely via mutation that:

But every indel is a mutation. It's really very simple. No matter what mechanism we will find that has caused these indels, if we do indeed need to find mechanisms that aren't yet discovered that cause them, will still be a mutation. Ie, something that changes the genome.

- you think they don't exist (you assume that mutation is the default/only? mechanism)

Because any change in genome is called a mutation. What's so hard about that? We don't know all mechanisms causing mutations yet, we don't know all mechanisms responsible for the specific indel mutations in the paper yet (the last because we haven't looked in depth yet). But all changes in genome are called mutations, so any new mechanism discovered will also be called a mutation. It's really that simple.

- I think that they must arise via some as-yet-unknown-mechanism (I assume they do exist)

And I have no idea why.

Fair?

The good news is that genomic research will eventually determine whether significant difference-critical insertions exist. Then we'll know. I'll gladly change my mind when the evidence calls for it.

 

[jnhofzinser]

In the context of Pete's Quiet Thread post, the only mutations that were under consideration (called "beneficial") are those that contribute to organism (in this case human) uniqueness. More recently, you have (on a number of occasions now) correctly pointed out that there are plenty of mutative mechanisms that result in insertions and deletions. But you don't address whether or not these mutations contribute to organism uniqueness. This appears to be the source of most of our disconnect. It is as if you won't let us talk about genomic phenomena that contribute to the uniqueness of an organism because we don't know which phenomena those are. Now while that may be true, we can likely infer which phenomena are NOT "interesting" -- and many of the mutative mechanisms that you have mentioned result in phenomena of that sort.

 

[jnhofzinser]

I'd like to bridge the current disconnect (which is likely my fault), if possible.

Consider, please, two cases on "equivalent" divergence:
Case A: the divergence between chimpanzee and human genomes was "maximum entropy" (i.e., spread across point mutations only)
Case B: the divergence between chimpanzee and human genomes was "minimum entropy" (i.e., essentially one big substitution [=insertion/deletion])

Now it is clear that the reality as has been observed is somewhere in between these two cases.

But let's (hypothetically, now) imagine Case B. The evidence (in Case B, not in real life) is that a single mutation has caused the evolution represented by the divergence between chimpanzees and humans. How do we respond? Do we say, "sure: an insertion is a mutation, no problem" or do we say "wow! the likelihood of that mutation is infinitessimal [as it represents a 'hopeful monster' type of evolution]".

Ok, now back to reality. I am assuming (yes, assuming: this is NOT a conclusion from the paper, and I have never made such a claim) that, represented in the divergence between chimpanzee and humans there are insertions that are representative of Case B. You folks are saying "sure: an insertion is a mutation, no problem." I am saying "wow! the likelihood of that mutation is infinitessimal [as it represents a 'hopeful monster' type of evolution]"

I recognize that the disconnect might very well be due to the fact that my underlying assumption (that is, that there are Case-B insertions) may be in error. However, we do not yet have the evidence to determine this one way or the other.

 

[Tomk80]

In the context of Pete's Quiet Thread post, the only mutations that were under consideration (called "beneficial") are those that contribute to organism (in this case human) uniqueness. More recently, you have (on a number of occasions now) correctly pointed out that there are plenty of mutative mechanisms that result in insertions and deletions. But you don't address whether or not these mutations contribute to organism uniqueness. This appears to be the source of most of our disconnect. It is as if you won't let us talk about genomic phenomena that contribute to the uniqueness of an organism because we don't know which phenomena those are. Now while that may be true, we can likely infer which phenomena are NOT "interesting" -- and many of the mutative mechanisms that you have mentioned result in phenomena of that sort.

There are a number of reasons for the disconnect I think. The first is your refusal to call insertions and deletions mutations, though I have no idea why. I have no idea what you would consider in insertion that is not a mutation, since per definition all insertions are mutations, regardless the mechanism behind it.

Second, we have no reason to think that the mechanisms we know now that are responsible for insertions and deletions cannot contribute to organisms 'uniqueness'. Now, a problem with this, as with Pete's original post, is the small availability of information on the subject.

As Pete originally pointed out, information on rates of beneficial mutations is scarce. The reason for this is that they are so hard to point out. The only mutations that are easy to investigate are those that give a major disfunction. Even mutation that give a slight disadavantage are hard to spot. So his use of mutation rates was some of the only information available.

Now, with the problem of deletions and insertions, we encounter the same problem, but on two fronts. First, insertions and deletions are only recently looked at in comparisons between organisms, so there is very little information on the subject. I have found some references on different varieties of maize, and insertions that are spotted in those. But as of yet, I could find very little information on how often substitutions occur in comparison to deletions or insertions and how insertions relate in different organisms. And then there is the problem of estimating a beneficial mutation rate, which is the same as with substitution mutations. Most information we have on these insertions and deletions is from studies on diseases where genes malfunction because of the insertions. This is because these are easy to spot, as the disease is easily recognized. This does not mean that these insertions cannot have other effects when they occur on other places in the genome, just that we haven't done much research on that (for two reasons, the first is that we have no idea how we should look for that, the second is that at present that knowledge just isn't very usefull for things that people will give funding for).

But I'm still curious as to why you think the mechanisms we know as present that cause insertions and deletions cannot contribute to organisms 'uniqueness'. I'm very much at a loss as how you describe 'uniqueness' and what you think contributes to that 'uniquenss'. I'm also very much at a loss as to what you consider 'new code' and why you think the current mechanisms of insertions that we know cannot account for this.

To give an example. Dogs and wolves differ a lot in their brain structure, both in the brain mass relative to the dog/wolf and in specific structures that are bigger or smaller. Would you describe such a difference as 'uniqueness'? Now, we know that a lot of this difference is especially caused by a differential expression of the genes responsible for different areas of the brain. Would you accept that as a cause for the 'uniqueness'? Now, we know that differential gene expression can either be caused by a duplication of genes (which, interestingly, can sometimes be regulated by the cell itself) or by regulatory sequences of the cell. The lenght of such a regulatory sequence seems to make a difference there, or the space between different regulatory sequences. So an insertion or deletion could in that way have an effect on the expression on the gene, hence contributing to the organisms 'uniqueness'. We know of insertions causing such increases and decreases in regulatory sequences from diseases. Is it then strange to think that we can explain the divergence between organisms, and organisms 'uniqueness' with that mechanism? And what particular reason do we have to think that insertions cannot have accounted for such divergences, other than personal incredulity?