Talk:Neutral theory of molecular evolution

From Wikipedia, the free encyclopedia
Jump to: navigation, search
WikiProject Genetics (Rated C-class)
WikiProject icon This article is within the scope of WikiProject Genetics, a collaborative effort to improve the coverage of Genetics on Wikipedia. If you would like to participate, please visit the project page, where you can join the discussion and see a list of open tasks.
C-Class article C  This article has been rated as C-Class on the project's quality scale.
 ???  This article has not yet received a rating on the project's importance scale.
Note icon
It is requested that a photograph, photographs or other relevant image be included in this article to improve its quality.
WikiProject Evolutionary biology (Rated C-class, High-importance)
WikiProject icon This article is part of WikiProject Evolutionary biology, an attempt at building a useful set of articles on evolutionary biology and its associated subfields such as population genetics, quantitative genetics, molecular evolution, phylogenetics, evolutionary developmental biology. It is distinct from the WikiProject Tree of Life in that it attempts to cover patterns, process and theory rather than systematics and taxonomy). If you would like to participate, there are some suggestions on this page (see also Wikipedia:Contributing FAQ for more information) or visit WikiProject Evolutionary biology
C-Class article C  This article has been rated as C-Class on the project's quality scale.
 High  This article has been rated as High-importance on the project's importance scale.

Numerous discussions[edit]

I think that the first two lines need clearing up - there is a weasel word in there, and i am not convinced that it should start with a sentence saying what the theory is NOT a criticism of.Hectorguinness 11:52, 16 October 2007 (UTC)

I'm going to edit the following sentence (from the second paragraph in the overview): "That is, these differences do not influence the fitness of either the species or the individuals who make up the species" (emphasis mine) to "That is, these differences do not influence the fitness of the individual organism."

To refer to the 'fitness of the species' is to imply that such a concept exists among species, and thus that selection at the species level exists. While my personal inclination tends to Gould's side of the argument, in favor of species selection, most biologists range from highly skeptical to skeptically agnostic with respect to species selection. To my knowledge, Kimura, Ohta and those involved in the neutral theory discourse take no position on species selection. As such, the current phrasing represents neither the views of the "neutral theorists" nor those of mainstream evolutionary biologists. That said, I make no pretense to have read the entire (vast) body of neutral theory literature, so if the person who contributed this sentence has a contrary reference, she/he is invited to revert and cite it. —Temptinglip 07:27, 1 November 2006 (UTC)

I don't understand why this page is titled "netural theory of molecular evolution", rather than just the "neutral theory of evolution". I think that the idea of neturalism existed before we examined it on a molecular level, and even if it was originally restricted to the molecular level, I think that it is generally applicable to all levels of phenotype. adam

The title is, in some sense, a proper noun. Kimura originally called his theory the "neutral theory of molecular evolution." The phrase "neutral theory of evolution" is a generalization, but one that is ultimately derived from (and exemplified most clearly by) Kimura's theory. The impact of "neutral" change on evolution is fiercely debated, with skepticism increasing as the scale of focus changes (molecular to morphological to behavioral to population and so on); neutral evolution is most widely accepted at the molecular level, so the specificity of scale is not only vestigial, it is currently relevant. —Temptinglip 06:43, 1 November 2006 (UTC)

Is "degerate" a technical term for multiple codons coding for a particular amino acid? If not, this should surely be eliminated, as it is not NPOV. Redundancy need not indicate bad design. --Ryguasu 05:29 Feb 5, 2003 (UTC)

"Degenerate" does not imply a value judgement. It's a technical term in many fields--originating from statistics would be my guess. Distinct quantum states in an atom (which are defined by the values of their quantum numbers) are said to be degenerate if they have the same energy. But these "degeneracies" can sometimes be "split" by sticking the atoms in an electric field, under which conditions the different electronic orientations may no longer be equally stable (i.e. have the same energy). 168... 07:05 23 May 2003 (UTC)

The concept of degeneracy is widespread in evolutionary biology literature. While the particular example of the degenerate genetic code (64 codons but only 20 amino acids) is probably the most common, the concept is a broad one. In general it refers to the property of a system to remain stable in the face of change. Naturally, such a concept is relevant to any discussion of neutral evolution: degeneracy decouples, or at least weakens the link between genetic code and phenotype; since selection acts upon phenotype, not genetic code directly, degeneracy thus also weakens the precision with which selection can influence the genetic code. Degeneracy in-and-of-itself has been the focus of discourse in evolutionary biology, particularly as it relates to the origins of complexity, as this paper in PNAS demonstrates. Interesting stuff, in my view. (see also: Degeneracy of the genetic code) —Temptinglip 05:36, 1 November 2006 (UTC)

I changed the emphasis of the first 'graph to be about the differences we see between species instead of the effects of mutations as they arise. An edit by Lexor suggested to me that he was trying to push it in that direction, which coincides with my own preference. I'm open to reversion if my interpretation is wrong. Meanwhile, I think there has to be some explanation for why changes at the species level accumulate at the rate of mutation. If it's true, my inference is that fixation must be assumed to be fast compared to mutation. 168... 08:33 23 May 2003 (UTC)

The reason that the substitution rate is equal to the mutation rate is this:
Substitution rate = number of new mutations * probability of a new mutation "fixing"
prob fixation = 1/2N (where N = population size), it's simply the initial frequency of a new mutation in a population, which is normally only in one copy. This is only true for neutral mutations, btw. For non-neutral mutations, a more complicated expression is necessary.
number of new mutations = population size * mutation rate = 2N * u (for diploid organisms)
hence K (subst. rate) = 2Nu * 1/2N = u = mutation rate
if you want to add a sentence/section explaining that intuitively, go ahead. I will then add the more technical section at the end.
Fixation normally occurs in 4N generations which is normally << 1/u = (time before next mutation), so you are correct there, but it's not the cause of the fact that the substitution rate = mutation rate. -- Lexor 08:43 23 May 2003 (UTC)

I don't see why P(fixation)=initial frequency. I'd have thought it came from some heavy math, but you seem to be saying it's direct and intuitive. Maybe I'll get it after some sleep. 168... 08:53 23 May 2003 (UTC)

Well it can be understood, if not dervied, both ways (heavy math as well as intuitively). It's intuitive in the sense that if you have a small pop size (N), then your initial frequency 1/2N will be high, and therefore drift is more likely to "fix" an allele that is already in higher frequency (as successive generations of "sampling" increase the frequency of that allele). The actual derivation of this uses diffusion theory, but it's not necessary to talk about that in this article (at least at the beginning), simply note that the smaller the pop size, the higher the prob. that any given new mutation will "drift" to fixation.

Also I can't help noticing that the RHS of your first equation seemingly doesn't have units of time, which the LHS suggests to me it ought. 168... 08:55 23 May 2003 (UTC) Nevermind, the units business becomes clear lower down.

IF the article is going to lead by mentioning early resistance to the model, I think it needs some spelling out: who opposed the theory, and why did they think it contradicted Darwinian theory? I think this is important, to make the article more informative. It is my impression that the early opponents came from molecular chemistry and really didn't understand population genetics at all (and thus did not understand the modern synthesis). Am I wrong? Eitehr way, someone please add some specificity -- or just cut it altogether, Slrubenstein

Well, the theory has an air of controversy firmly attached to it even among practioners, so I think it's apt to allude to it in the intoductory remarks. You have a good point though. I think the content you are suggesting would go well in the section about the debate. I'm not really equipped to write it though w/out some reading to freshen my memory. But that MIT external link is a great resource for anybody who wants to look. 168... 19:25 23 May 2003 (UTC)


re: the "this process" sentence, I think i see your point now, but I suspect it's based on hasty thinking. Consider a population of indivuals who all have the same "blank" allele. A mutation arises in one individual. With some probability it drifts to fixation (many don't make it) and swamps out the ancestor allele. The probability of a third allele coming into existence while this process is happening is assumed to be small (see above). At the moment of fixation, or thereabouts, the population or species is what I would call "changed" and evolution, in the common sense, has occured. The population is now back to where it was before: All members have the same allele, and the process repeats. Downward drift doesn't appear in this least as I understand it. 168... 19:56 23 May 2003 (UTC)

You misunderstand the process. Drift is a change in frequencies in alleles (due to random causes). An allele is one variant of a gene. As the frequency of one variant of a gene goes up, the frequency of another variant necessarily goes down; as the frequency of one allele goes down, the frequency of some other allele necessarily goes up. They are part and parcel of the same process. SO: you can say that a specific allele drips "up" or "down." But there is no such thing as "upward drift" or "downward drift," since drift always involves some alleles drifting up, and some drifting down. My change is accurate, and well-written -- and hardly does any damage to the point of this article. On a personal note, you really need to think about your exagerated fastidiousness. SLR

So long as we're getting personal all of a sudden, let me recommend to you that you take disagreements less personally and give people the benefit of not assuming they are idiots and out to get you. No matter how badly you evidently think I misunderstand drift, I truly can't imagine how you could think, if you were to stop and think for just a moment, that I don't understand that it goes both ways. That idea first appeared in the drift article when I put it there. Your statement about there being no downward drift is like saying nobody ever walks out of Macy's b/c people are always also walking in. 168... 05:05 24 May 2003 (UTC)

...There is virtually no article on Wikipedia over wheich all members agree completely about the phrasing and the content. You seem to believe -- in this and the genetic drift article but also on the founder's effect article -- that you must either agree with everything, or not get involved. You should get involved with any number of articles -- but you have to accept the fact that some people have other wasy of looking at things, or other ways of writing, that you do not like but that are valid and must be accomodated. (In this case, on drift, however, I am just right. But my point is, even if you really believe me to be wrong, does including this really damage the article, does it really invalidate the positive points you are making? I think not) Slrubenstein

Are you a cultural relativist on the laws of physics too? Look, we differ on a point of fact here. For some reason, you have not grasped nor specifically responded to the logic of my argument. I have no doubt in my mind that you have committed errors in Founder's effect, but I know you don't believe so, and so I have raised the matter in the discussion for others to decide. Why don't you take the same approach here. Or will we be reverting each other's work to the edges of the Wiki universe?168... 20:11 23 May 2003 (UTC)

About relativism, I have no idea what you are talking about. I take issue with many things you write, especially with how you write them. Believe it or not, I usually just accept them, out of respect for you as a contributor, and the project as a whole. I will only make a change when I am absolutely convinced that my change makes the text much clearer (not just clearer, but much clearer), or when I am certain my change makes the text more accurate or informative. I generally try not to delete content unless I am certain it is wrong. In the case of this article, I did not delete ANY content. I did, however, add content -- accurate content. You keep deleting it. Do not delete accurate content. Also, please consult -- no one owns a page or can dictate absolutely all content. Slrubenstein

I deleted what I view as irrelevant content. The sentence is not about drift per se. It's about the neutral evolutionary process, a special case of drift. Your sentence in effect removes content of mine which I believe is accurate. Hence you are deleting accurate content too, but directly _relevant_ accurate content. 168... 20:23 23 May 2003 (UTC)

Hey, guys, come to some sort of middle ground so the page doesn't have to be protected --Dante Alighieri 20:19 23 May 2003 (UTC)

OK. It is clear that this page needs intervention. I'll ask nicely that neither Slrubenstein nor 168... make any further edits to the page for the time being. I'm placing this article on the Wikipedia:Current disputes over articles next to Genetic drift. Let's give it a few days to let someone sort this out. --Dante Alighieri 20:31 23 May 2003 (UTC)
I think Dante is right, the page should remain unedited for a while. I tend to agree with Slrubenstein's reasoning here, but that is partly because I don't fully understand 168...'s point. I have to sleep now, but hopefully 168... can explain further and we can reach a consensus -- sannse 21:25 23 May 2003 (UTC)

168... Could you explain again why you believe drift cannot occur in both directions? -- sannse 20:27 23 May 2003 (UTC)

I'll expand on this later when I get the time, but the short answer is that the (very clear) topic of the sentence is allele whose progress we are following from birth until fixation. These are the alleles that change the species--the alleles that are born and become fixed. 168... 21:49 23 May 2003 (UTC)

Most genes have only one allele. As two species diverge from a common ancestor, neutral mutations accumulate in the gene. Why is that? (I ask rhetorically). If substitutions drifted out of existence as often as they drift to fixation, genes certainly wouldn't accumulate these substitutions. They accumulate b/c fixation is fast compared to how long one has to wait for a new mutation to crop up in the same gene. In other words, by the time a new mutation has occured in the version of the gene that one individual is carrying, the only version of the gene that it could be is the one with the mutation that just became fixed. So if the new mutation we waited for itself becomes fixed, we will have a gene with 2 mutations vs what we started with. The mutations will have accumulated. Many mutations will fail to become fixed--they will arise and drift out of existence--but any that succeed (typically) will arise in an "already mutated" gene and so simply to add to what was there. The time scale of ordinary drift is different than the one that concerns us in this paragraph. It's not where the story of this paragraph is. That's my understanding of this subject, which I have never studied formally. I could be wrong, but I can tell that SLR doesn't have a good handle on statistics or this material, and so I'm highly disinclined to simply defer to him, especially in absence of a rebuttal to my specific argument.

You might note how the text looked when Lexor last left it and/or before I lately came to it. On his talk page Lexor mentions that he has taught population genetics, the field which this topic squarely falls. He seemed to find no fault with those early versions, which only mentioned fixation (and that was no doing of mine). Then you could note the sentence that follows the fixation senetence in those versions and in the current one are about the rate at which substitutions accumulate. You might also look at Lexor's explanation in the math above. 168... 23:43 23 May 2003 (UTC)

I don't have figures on the issue, but I think to say "most genes have only one allele" is oversimplifying.
Since "most" can mean 50.00001%, 168 may be technically correct, although even so it is, as you say, an oversimplification. The only relevant study of which I know is a work by Prakash, Lewontin, and Hubby in 1969 in which they compared four separate populations of D. pseudobscura and estimated that 40% of the genes were represented by more than one allele; Dobzhansky considers this a vast underestimate. But even this is beside the point -- if we are talking about a recent mutation, then of course there are now at least two alleles, since mutation creates a new allele (old allele+new allele=two alleles). Until fixation -- which is by no means certain -- there must, by definition, be more than one allele (if there is one allele it is already fixed and there certainly would be no point in talking about "upward drift") Slrubenstein
To take the obvious example, there is more than one version of the eye colour gene. But that aside, I think it is important to express that this is not an inevitable process. The mutated gene may or may not reach fixation. It may become more common for a time, then drift downwards again and disappear from the population. So even if we consider one variation and its progress through this process, some alleles will disappear through drift. The genetic drift article makes this clear in the first paragraph.
It's great that Lexor is a professional in this area, that's a real asset to the Wikipedia, but that doesn't mean that every word he has written must stay exactly as it is. I'm sure he would be the first to agree with that. Everyone's work can be improved, expanded and clarified. I think that explaining that the process results in alleles disappearing from the population is an improvement to the article. Of course the section can no doubt be improved further from this point as well.
I'll unprotect, and let's work towards that improvement :) -- sannse 07:33 24 May 2003 (UTC)

Let me take back my designation of my question as rhetorical, because my explanation seems to have failed to convince you two. I would like you or SLR to explain why a gene, say for hemoglobin (although I don't know that this is a good example), has neutral, mulitple single-nucleotide substitutions in it that distinguish it from chimpanzee hemoglobin and presumably distinguish it from from the hemoglobin of our common ancestor? Why, the farther back you look in time, or the more distant the living relative you look at on the tree of life, the more neutral substitutions you see? Do you or SLR wish to deny that these are facts? I assume you don't. So what's the explanation you have to offer? These facts actually are what the paragraph is about--evolution of sequences. It's not about the basics of drift, which are in another article.

Meanwhile, I wish I had a hard number or a reference for you Sannse, but you will find that genes for which multiple alleles exist are the exception and not the rule. I believe it's something like 10-30%. (Hmmm. Actually, I may be conflating polymorphism statistics with heterozygosity statistics. Heterozygosity is very low, but polymorphism is higher. ANyway, it's not crucial to my argument). I think the reason this paragraph got me into trouble is that it uses the word allele. I should have made the focus the substitution, or the multiple substitutions that distinguish an allele from some arbitrary reference sequence. Yes, as a new allele rises to fixation the old allele declines. But none of that allele's older substitutions are lost, because they are present in the allele that is in ascent, b/c as I said, fixation is fast compared to the rate at which new mutations are "born." What we need for arbitration here is not people who understand drift, but someone who understands the neutral theory specifically. 168... 16:18 24 May 2003 (UTC)

168, if I didn't know any better, your defensiveness, obfuscation, and obsessiveness would make me think you were Lir in disguise. I certainly think you use the same tactics. First: this is just not something to argue about. My change in no way damages the article, and in no way contradicts any of your points. The simple fact that any other contributor thinks it is important should be enough reason to keep it, even if you do not understand it. The basic issue here is simple: you do not own this article. Second, to address your point about mutation -- what I added in no way contradicts the neutral theory of evolution, so further justifications for the neutral theory of evolution have no bearing on the change (your hemoglobin question is meaningless in this context -- the fact that in the course of human evolution some alleles drifted to a frequency of 0% neither contradicts, nor is contradicted by, the fact that humans and chimps are genetically different; on the contrary, it is part and parcel of the process through which humans and chimps diverged). The simple fact is this: evolution involves changes in allele frequencies. Allele frequencies can (and do) go up and down. Any movement up or down is a form of evolution, whether it is caused by random or selective forces, or by mutation. More specifically, drift involves allele frequencies going both up and down. A new allele (caused by spontaneous mutation) can drift up, and it can drift down. Both are forms of evolution. Finally, the fixation of one allele by definition involves the disappearance of another allel from the gene pool, and that diappearance is as much a significant evolutionary event as the fixation. Slrubenstein

Here you go again, SLR, challenging my sincerity and motives rather than responding to the specific argument I have taken the trouble to offer you. You certainly lead me to question your good faith at times, but you don't see me challenging it. Also notice that you haven't answered my question, which indeed is the central question addressed by the theory of neutral molecular evolution, and the topic of this article: How do sequences evolve? We all know what this evolution looks like: Neutral mutations accumulate. So how does that happen? What's _your_ theory?

Meanwhile, let's look at the two sentences:

The last one of mine that you changed:

Through the neutral evolutionary process, spontaneous alleles arise by mutation and, with some odds, drift to "fixation," meaning they come to predominate within a populations.

Notice the "with some odds." That's to say that the sentence addresses only a fraction of the new alleles of a given gene. Notice also that the sentence is describing only one process: "the neutral evolutionary process," which covers both spontaneuos mutations and the fixation of a subset of those.

This is the last one of yours:

Through the neutral evolutionary process, alleles spontaneously arise by mutation and, through drift, some alleles rise to dominance or become "fixed" in populations, while others disappear.

Yours is about new alleles in general and then it moves on to a statement about drift in general. You have deleted an explanation of a specific way in which genomes change, namely by accumulating neutral substitutions over time.

Finally, I don't believe for a second that you believe all opinions are equal. We both believe that there is right and wrong with respect to certain matters of fact (does gravity go as the inverse of r squared or the inverse of r-cubed? there is a right answer to this question). That is why I characterized some of your statements as cultural relativism (are you really an anthropologist? I would find it a bit surprising that you couldn't appreciate this point last time I made it, although clearly you don't give what I write any credence). I note that we also both believe there are some people with a better knowledge of the subject material of an article than others, and we both know that there are people who will opine and fight for their opinion even when its wrong.

Only one independent party has so far expressed any opinion on which of us has a better point here (a person who I don't think is claiming familiarity with the topic of Kimura's theory), and you would not be so ready to declare the election over if the person who just opined hadn't sided for the moment with you. 168... 19:47 24 May 2003 (UTC)

"As two species diverge from a common ancestor, neutral mutations accumulate in the gene. Why is that?" - because some of the mutations that occur become fixed in a population. Divergence from a common ancestor is inevitable (given no inbreeding) because mutations keep occurring, not because every mutation is inevitably fixed. I think we all actually agree on this point. We have said in various ways that not all neutral mutations are fixed. The dispute seems not to be on this point, but whether the paragraph needs to mention this. 168... you say that the paragraph refers only to the general trend of mutations accumulating, and so only to the upward drift (if I have understood you correctly). I feel that to explain the process effectively we need to include the smaller scale, and that means including the possibility of a mutation disappearing from the population. -- sannse

Thank you, thank you, thank you, sannse, for responding to my point. Since you seem to understand me, I admit I'm surprised your preference differs, but anyway I think it's perfectly possible to accomodate your view while retaining a sentence that conveys what I think needs conveying. We just need one sentence or phrase that is about mutations accumulating and one sentence or phrase to make it perfectly clear that others don't accumulate; i.e. the others rise and fall without fixing. But, wait, do you agree that to the general unlikelihood of a mutation that has fixed drifting away? Because if it has fixed, the only place a new mutation of the same gene can crop up is right beside it. 168... 19:55 24 May 2003 (UTC)
Humm, now you have lost me a little. A new mutation anywhere on the same gene results in a new allele by definition. As I understand it, "fixed" refers to a particular version on a gene becoming the norm through a population. It doesn't make a particular gene (or a particular base if we are looking at that level) immune to further mutation.....sannse
FIxed refers to an allele becoming universal in the population, to not any other version of the allele being carried by anybody. You are talking about exactly what I am talking about with the further mutations arising in the same gene. They arise in the eventually-to-be-deposed allele. But talking about allele's gets us or me into trouble. It's alleles that drift, but I have my eye on the mutations, not the alleles. A new mutation arises. It arises in the sequence of the fixed universal gene and with luck it drifts to fixation. Other mutations arise but don't get that far. Then in the fixed gene with one mutation there one day arises another mutation, which doesn't become fixed, but eventually some mutation eventually does and makes it to fixation. The first mutation I talked about is still there, even though the last allele drifted to zero. This is the simplest possible situation, but I believe the theory says it is most often what happens, b/c fixation is fast compared to the rate at which new mutations arise.
What's a more complicated scenario? Imagine a gene with 3 allele's, each with a frequency of 33%. One is an old allele that was fixed but has since drifted downward. The other two each carries a different single substitution with respect that older allele, in which they cropped up. The first cropped up when the old one was fixed. The second cropped up in the old one by chance when the old and the new were each at 50% frequency. What are the possible scenarios that could result in fixation? The old allele could rise back up to 100%. Then none of it's substitutions (i.e. none of the bases that differ from those of some older benchmark version of the gene) are lost. If either of the other two fix, then the species has a gene with one substitution more than the last time this gene fixed. So there is no way to lose a substitution even in this rarer, more complicated scenario. 168... 01:14 25 May 2003 (UTC)
...An allele that has successfully spread through the population may mutate again, and that new allele may spread and become the new norm with the old version of the gene becoming less common (or as we have described it, downward drift).... sannse
Yes, the above is still the scenario I'm describing.168... 01:21 25 May 2003 (UTC)
...Are we confusing two different types of 'drift' here?sannse
Maybe. I think what I made confusing was talking about the drift of alleles, while my focus is the drift of mutations within the sequence context (the "genetic background") of the old allele, so that even as they supplant the old they prop it up, by carrying it with them (minus of course, the one base they carry that's changed)168... 01:21 25 May 2003 (UTC)
We could talk of drift as away from the 'original' gene, in which case drift would always increase (the chances of a mutation restoring the original allele would of course be increasingly unlikely) or we could talk about drift as the increase or decrease of the frequency of a particular allele in a population. From the genetic drift article I understood the second concept to be the one we are concerned with here. -- sannse 21:20 24 May 2003 (UTC)
I like the mechanistic details to be transparent and I also don't want to employ an idiosyncratic use of a technical term like genetic drift. I'm not sure exactly what you're suggesting when you suggest we talk about "drift from the original gene." i.e. I wouldn't want to just leave it at that. Plus after fleshing it out, it might be I wouldn't like to give it that label; i.e. if we were talking about something less general or otherwise different than drift. But I'm not really sure what you're suggesting. 168... 01:29 25 May 2003 (UTC)
Ignore the last. It was an attempt to understand your use of the word 'drift' - I thought you might be using it in that way. But I see now you are not and I agree we don't want to introduce an idiosyncratic use of the term. I understand now how we were using the term differently. The allele drifts downwards; the mutation remains fixed. So the sentence as it stands is correct: "alleles spontaneously arise by mutation and, through drift, some alleles rise to dominance or become "fixed" in populations, while others disappear.", but needs an addition to explain that the mutations remain and accumulate. I don't think we want to use the word 'drift' in terms of mutations, from the genetic drift article the term applies to alleles and, as you say, we don't want to introduce variations on the use of the word. I've added a short sentence to the article to express this accumulation of mutations, perhaps you and Slrubenstein can review and improve it. I have to move house now, many thanks for the educational conversation :) -- sannse 09:17 25 May 2003 (UTC)

I've expanded the contentious sentence into a two or three new paragraphs, which are meant to make everybody's points clear. I realize that my point in the original sentence was cryptic, but thanks to the thinking I had to do to debate the issue here, I found I was able to make it very explicitly in the article, and because it is evidentally a subtle point, I think the article is much improved as a result. Of course, it would still be good to hear the opinion of Lexor or somebody else really up on this subject. 168... 18:36 25 May 2003 (UTC)

I think the new paragraphs are fine, but I disagree with the statement that "individuals with new substitutions arise rarely." Doing some simple math, if we assume a polymerase error rate of 1e-9 in humans (which is about right, i believe), this means a 3 kilobase gene has a probability of acquiring a mutation of about 3e-6 in a single replication event. Okay, fair enough... now, I don't know how many replication events there are from one fertilization event to the next, but let's be conservative and say 30.... This brings our odds of not having a mutation in our 3 kilobase gene to about 9e-5, in a single individual. If we have 5000 individuals in our population, then this means that there's about a .36 probability of a new mutation arising each generation. Is this rare, or is my math wrong? And this is only assuming DNA polymerase errors, never mind depurination events, thymine dimers and other such nonsense. Graft 00:56 26 May 2003 (UTC)

Graft, you write: "I don't know how many replication events there are from one fertilization event to the next, but let's be conservative and say 30.... " You lose me there. Are you considering sperm/egg probabilities? I can't tell what you have in mind. From my perspective, it seems to me what's relevant are the odds that a gamete contains a substitution in a particular gene of interest, multiplied times the odds that that particular gamete participates in a fertilization event, which contributes a new member to the population. Incidentally, does one really go by the DNAPol error rate? There is correction machinery, after all. Anyway, I'd be interested to know the numbers, if you or anybody else could surf them out or dig them up. 168... 03:52 26 May 2003 (UTC)

In order for a gene to be mutated from one generation (i.e., when I am a zygote) to the next (i.e., when my progeny is a zygote) it may acquire a mutation at -any step- from the point where it exists in the zygote to the point where it exists in the gamete (sperm or egg). So, if every replication event gives some odds of a gene being mutated (and 1e-9 is the error rate after all corrective machinery has been considered), when I go from zygote to blastula cell to mesoderm cell to gamete, every time the cell divides, there is some possibility of error, infidelity in copying. Graft 16:07 26 May 2003 (UTC)

Maybe you're assuming I know more about where sperm and eggs come from than I do. I agree that a mutation can come up anywhere in the lineage of sperm and eggs from embryo on, but if it doesn't arise until meiosis, only one gamete out of many will carry it. How long is the lineage that leads to a gamete? What and/or where are the "stem cells" for the gametes, and after how many cell divisions are they "born." I know e.g. that human females have all their eggs at birth.168... 16:26 26 May 2003 (UTC)

P.S. You can also find people quoting an error replication error rate of10^-10

It doesn't matter what happens in the other gametes. All that matters is, what are the odds that the fertilising gamete had an error in it, when compared to the progenitor zygote? These odds will be the product of the odds of an error at each replication step... i think this is pretty elementary, i'm fairly confident this is correct. As to the numbers I used, they may be off here or there, but I think the essential point still stands. I don't think substitutions in a particular allele can be considered "rare" in a population-wide sense. New mutations must be occuring in a large population all the time. In other words, I think it's probably rare for genes to actually be "fixed", barring tiny populations (like the famous four cheetahs). Fixation occurs when populations become reduced or separated, not when they are large and interbreeding. In such a population, multiple alleles must be rampant, and new substitutions fairly common. Graft 17:21 26 May 2003 (UTC)

Well, I believe I've read that heterozygosity is low in humans. Plus Lexor confirmed my inference that drift was fast compared to the rate at which individuals with new mutations are born. What if we do the math this way:

(10^-10 errors per base) X (1000 coding bases per gene) X (1/2 probability of a neutral substition ) X (5000 individuals per population) x (30 cell divisions per generation) = 0.075 neutral substitions per generation.

That implies 13 generations would pass on average between the birth of each new allele. 168... 17:48 26 May 2003 (UTC)

(Not that this counts as fast, since Lexor said the prob of fixation is 1/2N, or 1/10,000 for the population in the above example. I guess that means that on average 10,000 generations would have to pass to fix and allele. But I'm not sure.168... 17:57 26 May 2003 (UTC))

Actually, Lexor writes above that it's 4N generations on average that pass, or 20,000 in this case, before the next new allele arises. Also, though he replies "you are correct there" seemingly in response to my post saying "my inference is that fixation must be assumed to be fast compared to mutation", he may have understood me to be saying the reverse, because he writes "4N generations which is normally << 1/u = (time before next mutation)"; i.e. he reverses the "much greater than" symbols.168... 18:27 26 May 2003 (UTC)

Just to warn all concerned: I'm afraid I have little time left for this conversation, I'm in the process of moving house and my new home has no connection yet (sob!). I have to disconnect this computer tomorrow and will only have very limited on-line time for a while (when I can sneak onto someone else's computer ;) -- sannse 19:22 24 May 2003 (UTC)

What's your problem now, SLR? WHy are you deleting my explanation of how mutations accumulate? 168... 16:17 26 May 2003 (UTC)

I have not deleted your "explanation of how mutations accumulate," I have merely made a minor correction to your reference to drift. If you are refering to this line, "Because individuals carrying new substitutions in a gene are born rarely, all genes tend to become fixed for periods of time, which last until individuals with new substitutions arise," I deleted it for two reasons. First, it is not genes, it is alleles that become "fixed. Second (the reason I didn't just change gene to allele) I think the sentence is just wordy and redundant. I think the article already makes this clear, and it is not needed in this paragraph to make the point. It really goes without saying that things stay the same until they change. In any event, it seems to me that the article still provides an account of how mutations accumulate. On another note, re: the opening paragraph: I am not sure "genetic drift" is a "theory" -- I haven't seen it identified that way, although I haven't read all the literature. Do the people proposing the NTE call genetic drift a "theory?" It seems to me that the Modern Synthesis is a theory; population genetics is a field, a drift is a phenomenon or process, but in any case an empirical event that itself is an object of study and theorization. Slrubenstein

Maybe I just invented the usage of "fixed" in application to "genes." I'm not sure how it arrived in my head. I agree it doesn't belong if it turns out to be idiosyncratic, but on the face of it it's a sensible term: If an allele fixes there is no gene but the allele, and the gene isn't going anywhere soon, so "fixed" seems to apply. Regarding the deleted sentence, you have deleted some explanation, but I take your point that it may not be necessary. Regarding "the theory of," I don't think these words apply only to totally discrete and explicit intellectual products like Newton's theory of gravitation. Perhaps you'd prefer "on genetic drift theory", as in "diffusion theory." Even though physicists are more liable to say "diffusion theory" than the "theory of diffusion" to refer to the mathematics various people have developed for various types of diffusion problems, I wouldn't have thought there's a problem or a serious ambiguity created in an article like this to say "the theory of diffusion." As long as it's not capitalized. 168... 16:40 26 May 2003 (UTC)

When I wrote "The neutral theory is closely tied to and rests in part on the theory of genetic drift," what I meant was that the theory draws on the mathematics and principles of genetic drift,and that the phenomenon it describes is an elaboration on drift that includes drift. In any event, since the mathematics of drift is the work of population geneticists by definition, it strikes me as redundant and perhaps even misleading to cite the "work of population geneticists" as if it were an independent contributor to the theory. I also don't understand the desire to invoke the modern synthesis. Would the proponents of these two ideas mind telling me what they have in mind?

A separate issue is that I don't think the history of ideas and the apportionment of credit to fields is particularly interesting _first paragraph_ material for an article about a subject like this (a theory that people use every day). Citing drift in the way I did I thought was worthwhile, because drift describes what the neutral theory _is_; also because drift is more general and more important to biology arguably than is the neutral theory, so that readers should be invited to link out to learn about drift before they read more about the neutral theory (or they should be signalled to an area of ignorance that, given their interest in the neutral theory, they should consider repairing later). Obviously, one could go to town if the goal were to cite all the linkable ideas or fields to which drift pertains: genomics, molecular biology, evolutionary biology, phylogeny, taxonomy, genetics, evolution, statistics, homology, bioinformatics, DNA.... But that wouldn't make a very interesting entry point for an article like this. 21:06 27 May 2003 (UTC)

Drift is an observable phenomena, not a theory. The theory that the "Neutral Theory" relies on is the modern synthesis. Slrubenstein

You seem to be making a nomenclatural point, but I don't think it's justified. Search google with "theory of genetic drift" and you will get a lot of hits--a lot of academic hits. e.g. "Ecology & Evolutionary Biology 310" at U Conn and the "Mathematical Genetics" group at Oxford It's not a capital T theory, but there is a theory of genetic drift, by which I suppose people mean there's a coherent mathematical tradition, a family of equations and results attached to it.

I'm willing to accept that the modern synthesis is a theory of sorts too, even though I think "synthesis" hits the nail more squarely on the head. The weakness of the term in the context of this article, if one is using it only to allude to the mathematics of drift, is that it's a lot less specific than referring to drift.168... 21:38 27 May 2003 (UTC)

Well, I really don't think this is worth quibbling over -- I think both of us could make a case, and it isn't worth the effort on either part. I do think the current opening paragraph is an improvement over the previous version; I think it is clear and informative, and that is what is important. Given your own priorities, as best I understand them, I didn't think it could bother you.
I think drift is an observable phenomena and that (along with the empirically testable claim or hypothesis that most mutations are neutral) are what makes the NT compelling. I think the "modern synthesis" is a theory in that it provides a model for how evolution occurs, from which one may derive predictions and thus hypotheses. It is a clearly relevant theory in that someone who accepts only Darwin's theory of evolution via natural selecion will reject the NT, but someone who accepts the modern synthesis will not. Slrubenstein

You seem to have segued from nomenclature to philosphy of science. Or perhaps that's where you were coming from all along. Anyway, I appreciate you attempting to cater to my priorities, but I guess I didn't spell them out clearly enough. In fact, I do think the pop. gen. and modern synth. references would be better at the end of the intro section, and that they make the first paragraph less on-point and interesting. 168... 22:47 27 May 2003 (UTC)

I just posted a version that makes what I think are your points farther down in the article. Work for you?168... 22:59 27 May 2003 (UTC)

SLR, you said in the subject line of your reversion that you like your version because it "reads better." Do you think the sentences I put farther down read badly? Or do you think that inserting your points into the first paragraph reads better? If the latter, I'm surprised, because the points actually come as an interruption of the idea of the provocative effect that the theory had, and separate two sentences that used to be together. It seems undeniable to me that your paragraph is thematically more complex, and that it moves back and forth between ideas. If there's a case to be made for what I imagine is your perspective, I think it would have to be along the lines of "this is really important, it has to go up top," and then if that point prevailed, I think you'd have to rewrite the paragraph to make it "read better." But let's see if there are any independent opinions out there. 168... 00:00 28 May 2003 (UTC)


I don't think we should include that "cooling off of debate" sentence, because I don't think it fairly characterizes current understanding. Specific substitutions are more neutral than others, depending on situation - e.g. population size. That is, it's unfair to say one allele is "neutral" and another is "non-neutral" - rather, a specific substitution may be neutral, weakly selected, or not-at-all-selected depending on how the environment shapes selective pressure. There's thus no question of relative percentages since it's impossible to decide if a specific substitution would be neutral, and to what extent, outside of a given context. Graft 16:40, 10 Aug 2003 (UTC)

After looking at the MIT Web site on the history of the debate and this page in particular I'm reassured that it's reasonable to talk about percentages. It's not obviously apt, because the debate is so complicated, but in the end I think it's reasonable and probably the best solution. In contrast to your position that because of Ohta we can't say whether a mutation is neutral or not in the abstract, here's what Ohta says herself on that site

"If we look at all cases, there are some neutral mutations, some nearly neutral mutations, and some selective mutations."

Also look at the concurrance of opinion at the end of the page:

"we have John Gillespie's comments on my question about...He basically sides with Warren Ewen's comments...that it really does not make sense to talk about the truth, the correctness, of the neutral theory, or the nearly neutral theory, or even his particular selectionist models. It comes down to a matter of proportions...."

to which Richard Lewontin replies "I think his [Gillespie's] comment is right on"

and James Crow says "Me too."

In fact, I talked to Gillespie once and my characterization of the debate as having cooled and being about percentages was my recollection of how he summed it up to me, as someone new to the topic. 168... 17:25, 10 Aug 2003 (UTC)

Not that I think Ohta's comment implies that she assessed the neutrality her "cases" without regard to context. I only think it shows that after doing so she feels free to label them individually as neutral/non-neutral/nearly neutral, which seems to contradict your point. 168... 17:48, 10 Aug 2003 (UTC)

Excellent Review Article on subject[edit]

I suggest editors examine this excellent review article by Nei. I think it is a free publication. Regards GetAgrippa 16:48, 22 March 2007 (UTC) Nei M. Related Articles, Selectionism and neutralism in molecular evolution. Mol Biol Evol. 2005 Dec;22(12):2318-42. Epub 2005 Aug 24. Erratum in: Mol Biol Evol. 2006 May;23(5):1095. PMID: 16120807 [PubMed - indexed for MEDLINE]

Link! Graft 17:07, 22 March 2007 (UTC)
I don't think that this 'review' necessarily provides a NPOV, apart from the fact that the author views neither natural selection nor genetic drift as the primary driver of evolution. -AC

Another contiguous subject that I added the abstract for readers to determine do they want to bother to read it is related to directed mutations :Crit Rev Microbiol. 2003;29(1):25-35. Links The directed mutation controversy in an evolutionary context.Brisson D. Dept. Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794-5245, USA.

"Neo-Darwinists have long held that random mutations produce genetic differences among individuals, and selection increases the frequency of advantageous alleles. In 1988, Cairns et al. claimed that an environmental pressure can cause advantageous mutations to occur in specific genes to alleviate that particular pressure. Directed mutation, as proposed by Cairns, has been all but eradicated from evolutionary thinking. However, more than a decade of research spurred by the Cairns et al. paper has cast doubt on three neo-Darwinian principles: (1) mutations occur independently of the environment, (2) mutations are due to replication errors, and (3) mutation rates are constant. This mini-review explores the history of the controversy and the decade of research that followed so as to place it in an evolutionary context. Several of the cellular mechanisms and models that explain the increased genetic diversity in populations experiencing adverse environmental pressure are described. In most cases it is clear that the increased genetic diversity is due to breakdowns of cellular machinery or alleles evolved for a purpose other than increasing genetic diversity, rather than to cellular systems that have been evolutionarily selected to increase the genetic diversity in times of stress." Regards GetAgrippa 20:19, 22 March 2007 (UTC)

Well, I'm not impressed. The review is weak on ecological genetics, and the author claims facts which are disputable or just plain wrong. For example, after the significant claim "truncation selection apparently occurs very rarely in nature" he quotes two of his own papers which are full of mathematical population genetics, but derisible on the issue of field-based ecological genetics. This is important because the many, many claims of neutrality with respect to selection have been so very rarely shown to be the case in reality. Most claims have simply not been investigated empirically. Where they have been, it is often the case that selection is not only present, but hugely significant. In the field of polymorphism (which he summarises poorly and incorrectly) readers might like to check our Polymorphism (biology) article, which lays out some of the evidence from actual field experiments. Macdonald-ross (talk) 07:55, 22 February 2009 (UTC)

Nonsynonymous changes can be neutral![edit]

I didn't find any reference to nonsynonymous changes in this article.

Article non-accessible / Hard to Understand[edit]

I don't know about others, but I think this article is difficult to understand for a non-expert; it's pretty technical, but perhaps more importantly, it seems to discuss the history and development of the theory mixed in with the ideas itself. What do you think? I think it would clarify the article greatly to separate out the history into a section, and make another section that discusses the theory as it stands. Cazort 13:56, 14 October 2007 (UTC)

Correct: that development is definitely needed. Macdonald-ross (talk) 07:49, 26 February 2009 (UTC)

Imprecise formulation of the theory?[edit]

which states that the vast majority of genetic variation is selectively neutral.

Although this gets at a key idea in the theory, I don't think that this is precisely correct. In The neutral theory of molecular evolution (Cambridge U. Press, 1983), Kimura states: "The neutral theory asserts that the great majority of evolutionary changes at the molecular level...are caused not by Darwinian selection but by random drift of selectively neutral or nearly neutral mutants" (page xi). In other words, this is an answer to the question: "Of those alleles that arise through mutation and become fixed in a population, by what mechanism(s)/process(es) did they become fixed (and in what proportions)?" Kimura's answer to this question does not mean necessarily that a vast majority of genetic variation in a given population is selectively neutral. It means that most evolutionary changes (on the molecular level) occurred through stochastic processes. -AC —Preceding unsigned comment added by (talk) 03:12, 26 February 2009 (UTC)

This suggestion should be read with the previous comment about the benefits of an historical approach. 1) Kimura's original ideas must be accurately stated, b) Its weaknesses and defects listed, and c) Present status of theory, including significant differences of opinion, stated. This is indeed not an easy subject, and our account must be carefully planned. Macdonald-ross (talk) 07:57, 26 February 2009 (UTC)

While some scientists had hinted that maybe neutral mutations were widespread, like Sueoka (1962), a coherent theory of neutral evolution was first formalized by Motoo Kimura in 1968

This is not correct, either. Sewell Wright had a fairly detailed theory of neutral evolution prior to 1960. One of the main differences between Wright and Kimura is that the latter was doing his math during/after we started to learn about the molecular mechanisms of genetics. But Wright saw neutral processes as the major driver of evolutionary change. Like Kimura, Wright did not deny the role of selection in guiding adaptive evolution. But that's really the crux of the matter: how much evolution is adaptive? -AC —Preceding unsigned comment added by (talk) 15:53, 26 February 2009 (UTC)

Graur & Li (2000) Quote[edit]

I think this quote reads like a bad after-dinner speech, where somebody's aging professor, an intransigent and unyielding selectionist, was present, and you didn't want to embarrass him about it. Don't most of the summaries of the history of the debate finally admit that the neutralists won and the debate is over? Metzenberg (talk) 05:54, 20 May 2009 (UTC)

My reading of the literature since 2000 is that this is still a live area of debate and research. In any event, quotes and opinions in a WP article must be pinned to reliable sources published in refereed journals and publishers of repute. There is nothing wrong with Graur & Li as a source. Macdonald-ross (talk) 08:50, 20 May 2009 (UTC)
I'll second that. Although I get the sense that the question is becoming: "How much?" rather than "Which one?" --Pugettia (talk) 16:41, 25 May 2009 (UTC)
Graur & Li is an excellent source. The problem is, the quote is out of context. Metzenberg (talk) 09:58, 26 May 2009 (UTC)

Synonymous mutations not always neutral[edit]

Can a professional address recent discoveries showing that synonymous mutations are not neutral and may be quite beneficial or detrimental, and that such situations are not extremely rare? I have only read the Scientific American article by Chamary and Hurst (the latter seems to be the primary investigator for most of the studies alluded to in the piece). Aldebrn (talk) 15:00, 15 June 2009 (UTC)

Dating methods[edit]

Palaeoanthropologists typically use palaeomagnetism, uranium series dating, and cosmogenic isotope dating. If radiocarbon dating is to remain in the artical, then please site a reference. (talk) 01:25, 5 December 2010 (UTC)

Implications for evolvability in asexual populations[edit]

I'm sorry, it's absurd that one should have a detailed exposition of a single, unremarkable, paper dominating a significant portion of this subject's page. Since when were researchers allowed to advertise their work on Wikipedia? Perhaps it would be better to have a sentence on his work, with others, in a new section "recent research". But to have a big bulk of text on one paper (have a look at the where it's cited to see it's "influence") belittles the subject. — Preceding unsigned comment added by (talk) 09:58, 29 February 2012 (UTC)

I agree, this section should be deleted. From what I remember, the paper is about neutrality, but not about the neutral theory at all. I had been going to do the deletion, but first I had wanted to be thorough, and check my memory by looking at the paper. Meantime, I stashed the text in question into its own section as a holding device. This page needs a lot of work, I hope to get around to it some time. Joannamasel (talk) 14:34, 29 February 2012 (UTC)


This article needs a definition of "neutral" (or a wiki link) in the lead section. -- (talk) 20:02, 9 April 2014 (UTC)

Done Joannamasel (talk) 02:12, 13 April 2014 (UTC)