Darwin and neutrality

Posted 8 February 2007 by PvM

Various ID proponents have shown a confusion about Darwinism and neutrality, arguing that these concepts are contradictory rather than complementary and that the existence of one negates the existence of the other. Such a false duality is commonly found in the writings and musings of ID proponents who insist on elimination to infer the existence of one of many alternatives. So lets explore in further detail the concept of neutrality and its relevance and importance to evolutionary science (and by logical extension also the vacuity of Intelligent Design).

I am inclined to suspect that we see, at least in some [cases], variations which are of no service to the species, and which consequently have not been seized on and rendered definite by natural selection.... Variations neither useful nor injurious would not be affected by natural selection, and would be left either a fluctuating element, as perhaps we see in certain polymorphic species, or would ultimately become fixed.... We may easily err in attributing importance to characters, and in believing that they have been developed through natural selection;... many structures are now of no direct use to their possessors, and may never have been of any use to their progenitors.... [On the other hand,] we are much too ignorant in regard to the whole economy of any organic being to say what slight modifications would be of importance or not.

From: DARWIN, C., 1872 The Origin of Species, 6th ed. p. 60,88,181,182,184. New American Library of World Literature, New York (1958) As early as 1985, Hartl et al published a paper outlining what they called limits of adaptation: the evolution of selective neutrality and conclude that When considered from a certain perspective, the superficial inconsistency between Darwinian selection and neutral evolution disappears completely.

At this point, many mutations that result in small changes in activity will result in negligible changes in fitness and will be selectively nearly neutral. We propose that this process is a mechanism whereby conditions for the occurrence of nearly neutral mutations and gene substitutions can be brought about by the long-continued action of natural selection. Evidence for the hypothesis derives from metabolic theory, direct studies of flux, studies of null and other types of alleles in Drosophila melanogaster and chemostat studies in Escherichia coli. Limitations and complications of the theory include changes in environment or genetic background, enzymes with sharply defined optima of activity, overdominance, pleiotropy, multifunctional enzymes and branched metabolic pathways. We conclude that the theory is a useful synthesis that unites many seemingly unrelated observations. The principal theoretical conclusion is that the conditions for the occurrence of neutral evolution can be brought about as an indirect result of the action of natural selection.

Ref: Daniel L. Hartl, Daniel E. Dykhuizen , and Antony M. Dean LIMITS OF ADAPTATION: THE EVOLUTION OF SELECTIVE NEUTRALITY Genetics. 1985 Nov;111(3):655-74 Since 1985, much research has shown how neutrality is not only essential for evolvability but that neutrality is subject to selection (Toussaint). It should therefor not come as a surprise that science has found how neutrality or near neutrality plays important roles in evolutionary processes. Whether found in RNA evolution (Schuster, Stadler, Fontana and others), protein evolution, viral evolution, neutrality keeps popping up as an important and essential factor to the success of evolution. And lets not forget Sergey Gavrilets whose work has shown how the high dimenstionality of fitness landscapes of real biological systems opens up a whole new paradigm of 'holey landscapes'

My work (e.g., Gavrilets&Gravner 1997; Gavrilets 1997; Gavrilets 2003, Gavrilets 2004) has lead to understanding that the properties of multi-dimensional fitness landscapes are quite different from those implied in Wright's (1932) metaphor of rugged fitness landscapes. I have been advancing a refined view of fitness landscapes (holey fitness landscapes) focusing on nearly neutral networks of high-fitness genotypes extending throughout the genotype space. These networks provide a way for extensive genetic and phenotypic divergence without the need to cross any fitness valleys. I have shown that nearly neutral networks are a general feature of multidimensional fitness landscapes. I believe this theoretical result is of general and fundamental importance. I have studied the properties of these networks and holey fitness landscapes existing in a number of important population genetic models. See the first chapters of my book for more discussion of fitness landscapes.

Gavrilets work, not surprisingly, has remained ignored by most Intelligent Design proponents as it undermines their major premise that Darwinian evolution cannot explain the diversity of life because of the existence of large valleys that cannot be crossed. So it should not come as a surprise that Sewell Wright's selective landscape pictures of hill climbing are flawed and that the properties of high dimensional fitness landscapes are very different from low dimensional ones (Gavrilets, Harvey) Picture%201.png

Both figures from R Shipman, M Shackleton and I Harvey The use of neutral genotype-phenotype mappings for improved evolutionary search BT Technol J Vol 18 No 4 October 2000 In his PhD thesis, Harvey shows how the concept of 'optimized search' is inappropriate for evolution where the dimension of genetic space increases due to gene duplication and other similar processes. Remember how ID proponents made a 'big deal' out of the 'fact' that evolutionary processes cannot be innovative because of the fixed dimension aspect? Seems that gene duplication is but one way to show how such a position remains scientifically vacuous. As Harvey observes

However, it is generally accepted that the design of robust mobile robot control systems is highly complex because of the extreme difficulty of foreseeing all possible interactions with the environment; and the interactions between separate parts of the robot itself.

In other words, rational design of such systems quickly becomes unfeasible. So how to resolve this? Not surprisingly Harvey shows how evolution comes to the rescue. And while ID proponents have raised various objections to evolutionary algorithms, such as the claim that such algorithms can create apparent but not actual complex specified information (Dembski), a proper application and understanding of the concepts of evolution, high dimensional fitness landscapes, neutrality and drift and the fact that the dimension of the genetic space is variable all help understand why the objections by ID proponents are mostly vacuous. PS: A plug for Gavrilets' book "Fitness Landscapes and the Origin of Species"

Fitness Landscapes and the Origin of Species presents both an overview of the forty years of previous theoretical research and the author's new results. Sergey Gavrilets uses a unified framework based on the notion of fitness landscapes introduced by Sewall Wright in 1932, generalizing this notion to explore the consequences of the huge dimensionality of fitness landscapes that correspond to biological systems.

44 Comments

hoary puccoon · 9 February 2007

This is fascinating. I had considered neutral mutations and genetic drift as alternatives to Darwin's ideas, but, as is often the case in evolutionary theory, the truth is more complicated than that.
That should not, however, get Wells off the hook for playing his endless game of confusing Darwin's contribution to biology with modern evolutionary theory. Even if Darwin were completely in error on this particular point, it would have no effect whatsoever on modern biologists, whose work rests on the contributions of their immediate predecessors, not on taking an historical document, whether the bible or The Origin of Species, as gospel.

Larry Moran · 9 February 2007

I'm completely confused by your posting. What does this mean?

Since 1985, much research has shown how neutrality is not only essential for evolvability but that neutrality is subject to selection (Toussaint). It should therefor not come as a surprise that science has found how neutrality or near neutrality plays important roles in evolutionary processes. Whether found in RNA evolution (Schuster, Stadler, Fontana and others), protein evolution, viral evolution, neutrality keeps popping up as an important and essential factor to the success of evolution. And lets not forget Sergey Gavrilets whose work has shown how the high dimenstionality of fitness landscapes of real biological systems opens up a whole new paradigm of 'holey landscapes'

How can "neutrality" be subject to natural selection? That doesn't make any sense at all. And what does it mean to say that neutrality is essential to the "success" of evolution? What "success" are you talking about and how does neutrality contribute? Are you thinking that neutral mutations somehow help natural selection be more "successful"? Neutral mutations as just that—neutral. They are invisible to natural selection. Think of all those substitutions in junk DNA, for example. Neutral mutations can be fixed in a population by random genetic drift. Random genetic drift has nothing to do with natural selection. "Darwinism" refers to the belief that almost everything in evolution is due to natural selection. Thus, neutral mutations and random genetic drift are not Darwinian. Is that what you meant?

PvM · 9 February 2007

How can "neutrality" be subject to natural selection? That doesn't make any sense at all.
— Larry Moran

At first glance, it indeed sounds self contradictory, after all neutrality is by definition 'non selectable' since it has no selectable difference in phenotype. However, and this is important to realize, neutrality does contribute to evolution in at least two very different manners, affecting the potential for evolution also known as 'evolvability'. Walter Fontana is best known for his work in this area. While historically, neutrality has been seen as a conservative force adding to robustness of the genotype, neutrality also adds to the variability of the genotype. In other words, because of neutrality, a significant variability in genotype can exist even though there is no observable variability in the phenotype. What this means is that there exist a set of neutral pathways, which extend throughout sequence space and connecting clusters of similar phenotypes with clusters of different phenotypes. This means that in genotype space, phenotypically differences are connected via vast pathways of neutrality. This has been shown to be the case for instance in RNA where phenotypically different structures are connected via vast pathways of neutral genotype changes. This was already realized much earlier by Altenberg and we now have to distinguish between static and dynamic fitness, the latter one being known also as evolvability or the capacity to evolve. In fact, as Toussaint has shown, neutrality is an essential component to this capacity to evolve and through this, indirect effect, a selectable feature.

And what does it mean to say that neutrality is essential to the "success" of evolution? What "success" are you talking about and how does neutrality contribute? Are you thinking that neutral mutations somehow help natural selection be more "successful"?

In a way, yes. When pathways of continuous improvements are separated by valleys, neutral evolution can improve the ability to cross these gaps as I have attempted to show in the fitness pictures.

Neutral mutations as just that---neutral. They are invisible to natural selection. Think of all those substitutions in junk DNA, for example.

Yes, they are just that neutral and more.

Neutral mutations can be fixed in a population by random genetic drift. Random genetic drift has nothing to do with natural selection. "Darwinism" refers to the belief that almost everything in evolution is due to natural selection. Thus, neutral mutations and random genetic drift are not Darwinian.

But neutral mutations and selection are and since neutral mutations enhance the capacity to evolve, neutral mutations are not only evolutionary relevant but also help understand why selection can be successful. Let's provide for a thought experiment. Selective evolution has reached an island of relative optimality and cannot move further, however in genotype space, sequences can continue to evolve in a neutral manner, increasing the variability in the genotype while maintaining the present phenotype. In other words, neutrality affects evolution in the sense of genetic variability. However, these variabilities, which 'diffuse' through genotype space have no significant effect on phenotypes.... until... poof a single mutation takes the phenotype to a new structure and selection can work again. This means that one expects to see phenotypical stasis followed by rapid phenotypical change in evolution when neutrality plays a significant role.

Is that what you meant?

Nope. I am referring to the work by Alternberg, Fontana, Schuster, Stadler, Toussaint and Gavrilets which show how neutrality is an essential and selectable component of evolutionary theory. Without neutrality, evolution would have gotten 'stuck' on the relative optimum above.

PvM · 9 February 2007

See also Tom Ray's Evolvability page with links to other such pages as well as many relevant papers, including Complex Adaptations and the Evolution of Evolvability by Wagner and Altenberg

The problem of complex adaptations is studied in two largely disconnected research traditions: evolutionary biology and evolutionary computer science. This paper summarizes the results from both areas and compares their implications. In evolutionary computer science it was found that the Darwinian process of mutation, recombination and selection is not universally effective in improving complex systems like computer programs or chip designs. For adaptation to occur, these systems must possess "evolvability", i.e. the ability of random variations to sometimes produce improvement. It was found that evolvability critically depends on the way genetic variation maps onto phenotypic variation, an issue known as the representation problem. The genotype-phenotype map determines the variability of characters, which is the propensity to vary. Variability needs to be distinguished from variation, which are the actually realized differences between individuals. The genotype-phenotype map is the common theme underlying such varied biological phenomena as genetic canalization, developmental constraints, biological versatility, developmental dissociability, morphological integration, and many more. For evolutionary biology the representation problem has important implications: how is it that extant species acquired a genotype-phenotype map which allows improvement by mutation and selection? Is the genotype-phenotype map able to change in evolution? What are the selective forces, if any, that shape the genotype-phenotype map? We propose that the genotype-phenotype map can evolve by two main routes: epistatic mutations, or the creation of new genes. A common result for organismic design is modularity. By modularity we mean a genotype-phenotype map in which there are few pleiotropic effects among characters serving different functions, with pleiotropic effects falling mainly among characters that are part of a single functional complex. Such a design is expected to improve evolvability by limiting the interference between the adaptation of different functions. Several population genetic models are reviewed that are intended to explain the evolutionary origin of a modular design. While our current knowledge is insufficient to assess the plausibility of these models, they form the beginning of a framework for understanding the evolution of the genotype-phenotype map.

Now forward in time to Toussaint's Neutrality: A Necessity for Self-Adaptation (2002)

Self-adaptation is used in all main paradigms of evolutionary computation to increase efficiency. We claim that the basis of self-adaptation is the use of neutrality. In the absence of external control neutrality allows a variation of the search distribution without the risk of fitness loss.

More in depth information can be found in Toussaint's thesis.

David B. Benson · 9 February 2007

PvM --- This is most enlightening! Your comment just above certainly helped...

Popper's Ghost · 9 February 2007

And what does it mean to say that neutrality is essential to the "success" of evolution?

The notion of "success" or "failure" of evolution is incoherent. One can only have a success relative to a goal, but evolution has no goals. There's nothing that counnts as successful evolution or unsuccessful evolution.

Flint · 9 February 2007

The notion of "success" or "failure" of evolution is incoherent.

Seems to me that PvM's context made it coherent. Evolution as a process would stop if the ability to move from one adaptive peak to another were to be lost, and I think it's legitimate in that case to say that evolution has failed - at the very least it has failed to continue occurring.

GuyeFaux · 9 February 2007

In fact, as Toussaint has shown, neutrality is an essential component to this capacity to evolve and through this, indirect effect, a selectable feature.

I think this is saying that neutrality is selectable in meta-evolution.

David B. Benson · 9 February 2007

GuyeFaux --- meta-evolution? Definition, please?

GuyeFaux · 9 February 2007

I can't give a precise one, but I've googled it and this looks reasonable:
link

David B. Benson · 9 February 2007

GuyeFaux --- Roughly, the evolution of new strategies for evolving new operators.

Thank you for the rapid response and for the link.

Sir_Toejam · 9 February 2007

Seems to me that PvM's context made it coherent. Evolution as a process would stop if the ability to move from one adaptive peak to another were to be lost, and I think it's legitimate in that case to say that evolution has failed - at the very least it has failed to continue occurring.

what about if the ability to change was not lost, but if the relative selective pressures on any given population were constant over time? would evolution have "failed" in this sense, since observed phenotypic changes within the population would only be coming from neutral mutations? hmm, i dunno I would word it such a fashion as "failed", I would rather think "stalled". I've seen excellent arguments for the importance of neutral mutation in much of observed phenotypic change. However, none of this limits the potential for selection to act as a far larger force at any given time as well, whether we speak of environmental factors, or social factors (e.g., sexual selection). Let's go back to the "ability" issue for a minute. Couldn't one equally argue that the appearance of a delayed or even non reaction to temporary selective pressures in a given population be adaptive in and of itself? what if there is some unmeasurable "average optima" that has selected for resistance to change to temporary optima that are readily observable? would we conclude, based on any given timeslice of observation, that evolution has "failed" because we see delays or non-movement in the face of observed or calculated immediate optima? hmm. I guess I just don't see the viewpoint of "failed" evolution as particularly useful in thinking of the process overall.

Sir_Toejam · 9 February 2007

... as a kind of long winded version of exactly what GuyeFaux said above in one sentence.

David B. Benson · 9 February 2007

Sir TJ --- Nonetheless, worth it for the term 'stalled'.
This is a common problem in evolutionary computation, at least using the Simple Genetic Algorithm. The term is certainly better than 'lack of evolvability'.

PvM · 9 February 2007

Seems that the term success was poorly chosen and despite its context may have caused some concern to some. Despite all this, I think that the message is clear that neutrality is an essential component to self adaptation (Toussaint). Contrary to some persistent beliefs, neutrality can in fact be under selective pressures and resolve instances where selective evolution alone would have gotten stuck on relative optima.
Although, as the work by Gavrilets shows, most multi dimensional landscapes are nothing similar to the simplistic ones from our youth :-)
Search PT on Gavrilets and you will notice some interesting articles on his concept of Holey Landscapes.

Holey smokes indeed.

Sir_Toejam · 9 February 2007

Contrary to some persistent beliefs

just curious, are you referring to IDers here, or did you have some in the scientific community you are also thinking of? also, this:

neutrality can in fact be under selective pressures and resolve instances where selective evolution alone would have gotten stuck on relative optima.

sounds rather contradictory. How can neutrality be under selective pressures, but not explainable by looking at selection? Perhaps you might reword that a bit? Yes, one can get stuck looking at relative optima, but that does not negate the value of looking at slective pressures, rather it implies a limitation to examing relative optima, along the lines of what I mentioned above.

Henry J · 9 February 2007

Just wondering, does "stalled" in this context just mean that the gene pool has already found all (or at least most of) the easily reached improvements relative to the current environment?

Henry

Sir_Toejam · 9 February 2007

Just wondering, does "stalled" in this context just mean that the gene pool has already found all (or at least most of) the easily reached improvements relative to the current environment?

Just to clarify, in the context i used it, it more applies to the "appearance of current state" under mutliple potential optima, if that makes sense. Also to clarify, this isn't at all my field; I'm a behavioral ecologist (I work on fish behavior mostly), not a modeller, so while I might be familiar with some of the terminology and concepts, and certainly have decent educational background in evolutionary theory, I'm by no means an expert on modelling selection landscapes. I'm trying to work this out along with the rest here. IOW, the appearance of being "stalled" could mean that there is selection for neutrality between various optima (as addressed by Pim in the contribution and by further comments), so it appears as if there is little relative change, or it could mean there has occured some other limiting factor for that particular population (some genetic constraint, for example) that limits its ability to track changing optima. It would in either case appear stalled. In the second case, a neutral mutation might free the population to then continue to track the "otpima landscape" more "accurately". If I am understanding what you are describing correctly in your question, that would be a case where local optima have already been tracked. It need not be the case that optima be tracked 100% necessarily, so long as we see at least some phenotypic change as perceived optima change. I'm specifically applying "stalled" to the case where it does not appear that a population is tracking changes between differing optima. Moreover, getting back to tracking optima, something else I wanted to mention is that one of the reasons "optimal foraging theory" ran into practical difficulty is that it's rather rare to find any given population tracking conceived "optima" 100%. so then the term "otpimal" itself comes under debate as to its usefullness in practice. Not to say it hasn't been VERY useful in working out theory, and providing fascinating predictions to test (which in many cases HAVE further supported the use of optimal foraging theory). I have some great references on that if anybody cares to see field applications of optimal foraging theory (i just can't remember the specific references off the top of my head at the moment, but I do recall one having to do with Russ and Sally Holbrook testing some of the predictions in two species of surfperches, so I'm sure I can dig them up if anybody is interested). However, the concerns end up relating to the question: at what point can we realistically determine whether a population has tracked a particular optima as well as it possibly theoretically "could"? does it mean it is not behaving "optimally", if it only follows a given proposed optima 25% of the time? yeah, yeah, a debate best saved for another time and place, probably.

PvM · 9 February 2007

Me: Contrary to some persistent beliefs just curious, are you referring to IDers here, or did you have some in the scientific community you are also thinking of?
— Sir Toejam

Mostly amongst IDers but I believe that some of the recent findings and research related to neutrality are of interest to all. Neutral evolution is not just fixation of genetic drift.

Me: neutrality can in fact be under selective pressures and resolve instances where selective evolution alone would have gotten stuck on relative optima. sounds rather contradictory. How can neutrality be under selective pressures, but not explainable by looking at selection? Perhaps you might reword that a bit?

Sure, I will give it another try. Neutrality is a selectable feature since it can improve evolvability for instance in situations where selection alone would lead to getting stuck on local optima. Because of this, genomes with different levels of neutrality would compete and the one with higher levels of neutrality would be 'more fit' in an ever changing environment. Again, imagine a world where the genotype to phenotype mapping were not degenerate as it is right now. This would mean that any mutation would likely have a positive/negative effect. Once 'stuck' on a local extreme, evolution may not be able to cross the chasm when the environment changes. However, in a world with significant neutrality, the genome can 'explore' genotype space and 'diffuse away' from this island. Now, I understand that these are all very simplistic descriptors of what is happening but it may help understand how evolution 'resolved' the representation problem. Occasionally creationists have argued that this representation problem was a real problem for evolution. Altenberg and Wagner discussed the issue in Complex Adaptations and the Evolution of Evolvability

The problem of complex adaptations is studied in two largely disconnected research traditions: evolutionary biology and evolutionary computer science. This paper summarizes the results from both areas and compares their implications. In evolutionary computer science it was found that the Darwinian process of mutation, recombination and selection is not universally effective in improving complex systems like computer programs or chip designs. For adaptation to occur, these systems must possess "evolvability", i.e. the ability of random variations to sometimes produce improvement. It was found that evolvability critically depends on the way genetic variation maps onto phenotypic variation, an issue known as the representation problem. The genotype-phenotype map determines the variability of characters, which is the propensity to vary. Variability needs to be distinguished from variation, which are the actually realized differences between individuals. The genotype-phenotype map is the common theme underlying such varied biological phenomena as genetic canalization, developmental constraints, biological versatility, developmental dissociability, morphological integration, and many more. For evolutionary biology the representation problem has important implications: how is it that extant species acquired a genotype-phenotype map which allows improvement by mutation and selection? Is the genotype-phenotype map able to change in evolution? What are the selective forces, if any, that shape the genotype-phenotype map? We propose that the genotype-phenotype map can evolve by two main routes: epistatic mutations, or the creation of new genes. A common result for organismic design is modularity. By modularity we mean a genotype-phenotype map in which there are few pleiotropic effects among characters serving different functions, with pleiotropic effects falling mainly among characters that are part of a single functional complex. Such a design is expected to improve evolvability by limiting the interference between the adaptation of different functions. Several population genetic models are reviewed that are intended to explain the evolutionary origin of a modular design. While our current knowledge is insufficient to assess the plausibility of these models, they form the beginning of a framework for understanding the evolution of the genotype-phenotype map.

If the genotype phenotype mapping can be under control of selection, or if the kind of mutation can be under control of selection, then evolutionary theory can explain how evolution has been successful, in a reproductive manner, adapting to ever changing environments and conditions. Note that Wagner wrote their paper a decade or so ago and science has been slowly uncovering the nature of evolvability. Another way of looking at this is described in a 1996 paper Smoothing Representation of Fitness Landscapes the Genotype-Phenotype Map of Evolution (1996)

The genotype-phenotype map transforms the rugged valuation landscape of fitness values of genotypes into a smooth fitness function of phenotypes and thus facilitate the process of evolutionary search.

In other words, whether it be neutrality or high dimensionality, the 'landscape of fitness values' tends to become smoother, and thus facilitating the processes of evolution. The idea that proteins are islands of function within an ocean of disfunction, aka as the ID problem and popularized by Axe and ID proponents, may need to be revised based on these findings. In RNA space there have been some great examples of how neutrality and selectable mutations interact, leading to stasis in phenotype while still exploring genotype sequence space. In other words, stasis at the morphological level, need not mean stasis at the genetic level.

PvM · 9 February 2007

Just wondering, does "stalled" in this context just mean that the gene pool has already found all (or at least most of) the easily reached improvements relative to the current environment?

Stalled in the sense of variability versus variation

Similarly, variability of a phenotypic trait describes its propensity to change in response to environmental and genetic influences. The representation problem is thus about the variability of the phenotype and not directly about the genetic variation within populations. And the concept of developmental constraints (sensu Maynard-Smith et al. 1985) is about the limits of variability of traits caused by the way they are "coded" in the genome.

and

Evidence for genetic control over phenotypic variability is of capital interest to evolutionary theory (Sharloo, 1991). This literature shows that evolution by fixation of spontaneously generated variation does not just happen, but that evolution can also change the "rules" under which heritable variation is produced, i.e. the variability of the traits itself can evolve. Some characters that were variable can become fixed (Riedl, 1975, Stebbins, 1974), while others may become integrated into a tightly coupled complex of characters (Stearns, 1993) or others may gain variability after a developmental constraint was broken (Vermeij, 1970). Perhaps Schmalhausen was the first to clearly see the theoretical implications of a genetic control of variability (Schmalhausen, 1949). His key observations of abundant epistatic effects among mutations is just another way of observing that the genetic variability of a trait is under genetic control. Per definition, epistasis is the influence of the locus at one locus on the effects of alleles at other loci. It thus reflects the fact that the expression of genetic variation is under the influence of other genes.

These concepts are quite fascinating in that they combine robustness and evolvability under the same concept: neutrality. Neutrality is good for robustness as well as evolvability. If you thought that the concept that neutrality can be under control of selection sounds contradictory, the concept that neutrality affects both robustness and evolvability must surely sound even harder to 'swallow' :-) And yet...

Sir_Toejam · 9 February 2007

Neutrality is a selectable feature since it can improve evolvability for instance in situations where selection alone would lead to getting stuck on local optima.

my point in asking was this still seems to be invoking the value of selection, but in this case applying to the relative value of neutrality in a given fitness landscape. hence, getting stuck on a particular local optima could be considered to have negative fitness connotations relative to being neutral in the same fitness landscape. In that case, we can still use standard selection to explain the appearance of neutrality, yes? It would seem to me rather that we simply haven't calculated the relative fitness of neutrality vs. tracking local optima in a given fitness landscape, correct? hmm, or would that be simply positing the neutral position as an optima in and of itself? OTOH, I must be missing something, because this essentially would boil down to be similar to the argument of whether to be a specialist or a generalist in a given fitness landscape, wouldn't it?

Larry Moran · 10 February 2007

In other words, because of neutrality, a significant variability in genotype can exist even though there is no observable variability in the phenotype. What this means is that there exist a set of neutral pathways, which extend throughout sequence space and connecting clusters of similar phenotypes with clusters of different phenotypes. This means that in genotype space, phenotypically differences are connected via vast pathways of neutrality.
— PvM

That's just gobbledygook. It's a view that's based entirely on the adaptationist perspective. What you're doing is rationalizing a way that neutral mutations can help adaptation. Try thinking about neutral mutations in introns or junk DNA and see how your argument applies. Neutral mutations are not subject to natural selection in spite of what you said in your original posting. You would have been better off to just admit you were wrong instead of digging yourself deeper.

Let's provide for a thought experiment. Selective evolution has reached an island of relative optimality and cannot move further, however in genotype space, sequences can continue to evolve in a neutral manner, increasing the variability in the genotype while maintaining the present phenotype. In other words, neutrality affects evolution in the sense of genetic variability. However, these variabilities, which 'diffuse' through genotype space have no significant effect on phenotypes.... until... poof a single mutation takes the phenotype to a new structure and selection can work again. This means that one expects to see phenotypical stasis followed by rapid phenotypical change in evolution when neutrality plays a significant role.

What the heck does your "poofing" have to do with the fixation of nearly neutral mutations by random genetic drift? And what do you mean by the last statement? Is this an incorrect allusion to punctuated equilibria? I'm beginning to wonder whether you understand any of these concepts.

PvM · 10 February 2007

My My Mr Moran, you seem to be awefully negative and combative in your comments

That's just gobbledygook. It's a view that's based entirely on the adaptationist perspective. What you're doing is rationalizing a way that neutral mutations can help adaptation.
— Larry Moran

What I am doing is explain, albeit in a very simplified manner, how neutral mutations are important for the concept of self adaptation. I am glad that you consider this to be a rational approach however and indeed, these findings follow from at least a decade of research by people such as Altenberg, Fontana, Wagner, Schuster and Stadler and more recently by Gavrilets and Toussaint. For instance in RNA, it has been shown that vast neutral pathways exist which connect most any RNA structure (phenotype) making RNA space extremely well connected. This feature, also called scale free, seems to be an outcome of the genotype phenotype mapping as well as the preferential attachment and duplication. Toussaint, in his thesis work, has shown how neutrality is essential for self adaptation and Gavrilets has shown how fitness landscapes of high dimension tend to be 'holey'.

Try thinking about neutral mutations in introns or junk DNA and see how your argument applies.
— Larry Moran

You seem to be asking me to compare apples and oranges. Mutations in introns and junk DNA tend to be neutral because there is no function associated with them, at least as far as we know. Some parts of 'junk DNA' however can be observed to be strongly conserved. Nevertheless, my comments apply mostly to the coding DNA since that's where most of the evolution supposedly takes place.

Neutral mutations are not subject to natural selection in spite of what you said in your original posting. You would have been better off to just admit you were wrong instead of digging yourself deeper.
— Larry Moran

I do understand the confusion since indeed superficially the concept that neutral mutations are not selectable seems a foregone conclusion, but we have to be careful not to conflate two different situations. 1) Individual neutral mutations will not be selected for and will only come to fixation via genetic drift (or perhaps a selective sweep elsewhere) 2) the existence of neutral mutations, which affect the genotype phenotype mapping, however is selectable. In other words, organisms with a higher neutrality will have a higher evolvability.

What the heck does your "poofing" have to do with the fixation of nearly neutral mutations by random genetic drift?
— Larry Moran

Nothing, and that is not my argument. While fixation of neutral mutations by random genetic drift is indeed an additional mechanisms for mutations to become fixated in the genome, I am instead talking about the effect of neutral mutations on evolvability.

And what do you mean by the last statement? Is this an incorrect allusion to punctuated equilibria? I'm beginning to wonder whether you understand any of these concepts.

It helps understand why we may detect apparent stasis in morphology while in fact at the genetic level there is significant evolution going on in the form of increasing variation. Whether or not this has any relevance to PE, which is a slightly different answer to explain the fossil data is something to be determined. I am merely pointing out that neutrality will have effects (or lack thereof) on morphology (phenotype) despite the fact that at a genetic level there is a lot of variation happening. I think that Larry is confusing the concept of genetic drift, which I am not really addressing here, with the importance of neutral mutations on the potential to evolve (aka evolvability). Yes, genetic drift can lead to the fixation of neutral mutations, but that is not what I am considering here. I am considering how neutral mutations may help 'smoothen' the fitness landscape and 'fill in' the valleys between peaks, thus facilitating evolution and especially adaptive evolution. I suggest you read Toussaint, or if you are interested in RNA neutrality, the work by Wagner or Peter Schuster. There are some excellent powerpoint presentations which walk through the foundational concepts in RNA world. The work by Toussaint, and Gavrilets is more mathematical but also more interesting to DNA evolution.

PvM · 10 February 2007

my point in asking was this still seems to be invoking the value of selection, but in this case applying to the relative value of neutrality in a given fitness landscape. hence, getting stuck on a particular local optima could be considered to have negative fitness connotations relative to being neutral in the same fitness landscape. In that case, we can still use standard selection to explain the appearance of neutrality, yes? It would seem to me rather that we simply haven't calculated the relative fitness of neutrality vs. tracking local optima in a given fitness landscape, correct?

I believe your observation is a correct one, organisms which have no neutrality in their genotype phenotype mapping will have a different fitness landscape which would tend to be more rugged, while an organism with neutrality would have a smoother fitness landscape. Fitness is a complex issue though since fitness landscapes depend also on the mutation(s) involved. The fitness value will be similar for both organisms, however the shape of the fitness function will be smoother.

Sir_Toejam · 10 February 2007

Try thinking about neutral mutations in introns or junk DNA and see how your argument applies.

leaving aside for the moment that we aren't exactly sure what the real answer to that implied question is, it does not address the fact that while neutral mutations don't HAVE to affect the ability to track a given fitness slope, they in theory, COULD. It wasn't Pim who was raising this point, per se, but rather the authors of some of the references posted. So, I woul pose a question to you, Larry: Couldn't an apparent neutral mutation affect the ability to track a given fitness optima, say by removing some sort of genetic constraint that previously existed? I agree with you that it seems contradictory to say that truly neutral mutations themselves are subject to selection (otherwise, they wouldn't be neutral, which was one of the points I was trying to raise), however, that doesn't exclude the possibility that neutral mutations themselves might still lead to an overall increase in fitness indirectly, given the mechanisms posed by the papers above, and the simple one I posit above, yes? I guess the only real argument, and the thing i keep coming back to, is that what is being described might not actually fall under the definition of "neutral mutation", depending on how you define what a neutral mutation is.

Scott · 10 February 2007

This is fascinating stuff. Let's see if this layman understands correctly.

Individual neutral mutations are themselves (and by definition) not "selectable", ie are not effected by natural selection. However, the ability of a system of inhertitable traits (the genetic system, or genotype) to allow for neutral mutations is itself selectable.

For example, take an environment with two families of organisms. One family of organisms has a genetic system that has a low level of neutrality (few "neutral" mutations are possible). A second family of organisms has a slightly different genetic system that has a higher level of neutrality (many "neutral" mutations are possible). We're not just talking about differences in a few genes, but different *kinds* of genes or a different mechanism for expressing those genes. If both families reach the same local optimum for the given environment based solely on natural selection, the family with the higher neutrality has a greater ability to evolve further or faster than the other, able to take advantage of a different environment or change in the environment. Thus, the *ability* to have neutral mutations can be effected by natural selection.

Is that about right?

As for evolution being "successful", I think the definition is pretty obvious. Survival of the genetic line. If a genetically related group of organisms goes extinct, evolution has "failed" for that gene line. (Barring massive physical destruction of the environment itself, ala a massive proto-planet strike. You can't blame evolution for "failing" in that context.) If a group of organisms successfully survives a change in the environment through adaptation, evolution was "successful". Taken in its broadest sense, one could say our current means of evolution has been very "successful", as witnessed by the success of "life" in so many different environments. If we ever manage to move life to environments other than Earth, one could say that evolution has been ultimately "successful", able to live in any environment.

PvM · 10 February 2007

Individual neutral mutations are themselves (and by definition) not "selectable", ie are not effected by natural selection. However, the ability of a system of inhertitable traits (the genetic system, or genotype) to allow for neutral mutations is itself selectable.
— Scott

Yes, yes yes... you have done well grasshopper...

Henry J · 10 February 2007

In other words, if I'm understanding this, a tendency to produce neutral mutations may well be advantageous to the species. (The technical discussion kind of went over my head.)

Henry

Larry Moran · 10 February 2007

Individual neutral mutations are themselves (and by definition) not "selectable", ie are not effected by natural selection. However, the ability of a system of inhertitable traits (the genetic system, or genotype) to allow for neutral mutations is itself selectable.

Yes, I think that's what PvM is saying but it's totally ridiculous when you think about it for more than a second or two. The concept postulates a primitive organism that had no neutral mutations (or fewer neutral mutations). All of a sudden a mutation arose that allowed for more neutral mutations. The individual carrying that mutation was more "fit" than other individuals in the population because its descendants had the possibility of evolving faster at some point in the distant future. If you believe that, I'd like to talk to you about some swampland in Florida. There's no evidence that you can have variability in the rate of neutral mutations but variability is a requirement for natural selection. Not only do you need variability but it has to be under genetic control. Would anyone like to create a just-so story that does this? I'd like to identify the genes that are being positively selected in order to maintain a high rate of neutral mutations to enhance evolvability. Which genes should we look at?

GuyeFaux · 10 February 2007

...may well be advantageous to the species.

Indeed, what units of selection are we talking about? Certainly not genes, and not even individuals (hence the term "neutral"). So what, are we talking about populations? Species? Or, species having the same operators?

Henry J · 10 February 2007

Re "Indeed, what units of selection are we talking about? Certainly not genes, and not even individuals (hence the term "neutral"). So what, are we talking about populations? Species? Or, species having the same operators?"

Unless I missed the point of the article, it's the genes that cause the increase in neutral mutations, not the neutral mutations themselves, that are advantageous and therefore selected. Therefore it is (if this hypothesis is correct) selected on an individual basis, if an individual has genes that make it and its descendants more apt to produce neutral mutations.

Henry

Anton Mates · 11 February 2007

The concept postulates a primitive organism that had no neutral mutations (or fewer neutral mutations). All of a sudden a mutation arose that allowed for more neutral mutations. The individual carrying that mutation was more "fit" than other individuals in the population because its descendants had the possibility of evolving faster at some point in the distant future.
— Larry Moran

I'm not sure the "distant future" part is particularly a problem. Isn't that the favored explanation for sexual reproduction? Sexual organisms have an edge because their descendants have the possibility of picking up beneficial traits from the rest of the population, rather than having to acquire everything new through mutation--they can evolve faster. Why couldn't it work similarly with a tendency toward neutral mutations? Certainly it's hard to imagine a genetic mechanism for promoting all sorts of neutral mutations--if organisms could vet their own mutations as good/bad/neutral, natural selection would be unnecessary. But couldn't certain classes of mutations which are particularly likely to be neutral, like synonymous substitutions, be favored? The Toussaint papers suggest codon bias as an example of this.

I'd like to identify the genes that are being positively selected in order to maintain a high rate of neutral mutations to enhance evolvability. Which genes should we look at?

You wouldn't need to know that to demonstrate selection. There's a lot of empirical work on parasitism pushing hosts to switch from asexual to sexual, which doesn't depend on knowing the actual genes involved. Likewise, if there were genes raising the neutral mutation rate I would think they'd be selected for by high parasite/pathogen densities, or some other source of rapid variation in the fitness landscape. I haven't seen any actual evidence for this, though.

PvM · 12 February 2007

Yes, I think that's what PvM is saying but it's totally ridiculous when you think about it for more than a second or two. The concept postulates a primitive organism that had no neutral mutations (or fewer neutral mutations). All of a sudden a mutation arose that allowed for more neutral mutations. The individual carrying that mutation was more "fit" than other individuals in the population because its descendants had the possibility of evolving faster at some point in the distant future. If you believe that, I'd like to talk to you about some swampland in Florida.

So is this the only scenario you can imagine? There are quite a few more steps to the origin and the evolution of the genetic code, and no, it's not the organism that evolves, but we all know this don't we? I have provided various relevant papers and names of authors who have done the in depth research that Larry seems to be unaware of and thus ridicules. But our ignorance need not be a reason to not further educate ourselves.

There's no evidence that you can have variability in the rate of neutral mutations but variability is a requirement for natural selection. Not only do you need variability but it has to be under genetic control. Would anyone like to create a just-so story that does this? I'd like to identify the genes that are being positively selected in order to maintain a high rate of neutral mutations to enhance evolvability. Which genes should we look at?

Uh, you are familiar with the degenerate nature of the genetic code aren't you? Now I understand that these novel concepts may be quite confusing but the research on this topic have gone to great length to show the relevance, and necessity of neutrality on evolvability but I have to admit it's not your granddaddy's version of population dynamics anymore. Check out the work by Mark Toussaint, his thesis is online. Also check out the work by Wagner and Schuster on RNA evolution.

PvM · 12 February 2007

In other words, if I'm understanding this, a tendency to produce neutral mutations may well be advantageous to the species.

And essential to self adaptation/evolvability

Anton Mates · 12 February 2007

Uh, you are familiar with the degenerate nature of the genetic code aren't you? Now I understand that these novel concepts may be quite confusing but the research on this topic have gone to great length to show the relevance, and necessity of neutrality on evolvability but I have to admit it's not your granddaddy's version of population dynamics anymore. Check out the work by Mark Toussaint, his thesis is online. Also check out the work by Wagner and Schuster on RNA evolution.
— PvM

So far as I can see, none of your cited papers actually present evidence for neutral-mutation-promoting alleles which have been favored by selection. They generally argue that a high neutral mutation rate is beneficial to a population; but that doesn't imply that the rate is actually under selection, merely that it would be under selection if such alleles existed. The degenerate code could well be a product of such selection, but: a) there's at least two other competing families of hypotheses for its origin, namely stereochemical and biosynthetic; and b) that code went to fixation a couple billion years ago in most organisms, so I don't see that it could provide much evidence for neutrality selection in modern organisms.

Roland Anderson · 12 February 2007

A layman's understanding: please feel free to correct.

First, the error I made when I read this post to start with was confusing "neutral mutation" with "mutation in junk DNA". I have a feeling other commenters might have made the same mistake. Of course neutral mutations happen in coding DNA as well.

It seems to me that this could be used as a good example of selection acting at the level of the gene.

The trait which is being selected is the trait of coding for proteins in the way which allows for the most neutral mutations. Let's call it the "flexible coding" trait. We assume for the sake of the argument that this trait is under genetic control. I don't know how such control would be exerted.

In a population some of which have flexible coding and some of which don't, a new mutation arises which changes a coding section of DNA which in some members is flexibly coded and in others isn't. The mutation is such (a frame shift, perhaps?) that the mutations which previously were neutral are now no longer so: the proteins produced by the differing versions of the gene are now different, or have differing effects.

Now, it seems to me that the part of the population with flexible coding is more variable than the other part, which means that it is more likely that among them will be variants which can take advantage of potential beneficial effects of the mutation (although there will be others who are much worse off - which is why this is gene-level and not individual-level selection). There may not have been a one-step-at-a-time path through the space of genotypes which would have brought about this change, but the flexible coding allows "hidden" variation which can come in useful in the presence of other mutations. The new selectable traits have come about thanks to the hidden variation, which makes the variation itself a selectable trait. This is how the fitness landscape is "smoothed".

The point for me is that it is the trait of flexible coding which is being selected for through the differential reproduction of the individuals who do or do not carry it, and therefore the genes (if genes they be) which code for it. Obviously it's necessary that variation in flexibility of coding is a heritable trait for this to work, and also that the genetic code itself is degenerate, otherwise neutral mutations in coding DNA might be too rare for this effect to happen.

It's also selection at the gene level (assuming that genes are responsible) because (in sexual populations at least) individuals don't replicate - they only reproduce.

M.A. · 13 February 2007

I wouldn't mind if somebody here speaks English for a while.

My take of Darwin's statement is that there are things that appear in an organisms Phenotype that may or may not be uniformly present in all members of a species, and may or may not be due to Natural Selection. These things, more common in complex organisms, might be handy in the future in response to selective pressures. We just don't know.

I don't understand the article by D. Hartl, where he states:
"occurrence of nearly neutral mutations and gene substitutions can be brought about by the long-continued action of natural selection."
I thought that gene mutations were just a natural part of life, that they occured regularly, and might (or might not) have Any effect upon the Phenotype of the organism vs. Mr Hartl's view where these genetic mutations/gene substitutions are caused by natural selection.

Is neutral mutation a description of genes (genotype), or looks and function of an organism (phenotpye)?

If Genetic, these neutral mutations are expressed Less in large organisms, Right? Due to either influence of other genes, or recessive/dominance stuff.

Little things have fewer genes, and Any mutation is less likely to be a neutral mutation, as each gene is likely to be expressed in its Phenotype.

Small populations (and Little things) are likely to be affected by Selective Pressure of various types.

Large populations (and Large Organisms carrying more neutral mutations) are more likely to survive Selective Pressure. Individuals may not survive, but the species is more likely to survive,and adapt.

Do I have it right... or close?

I'm not even going to comment on multi-dimentional fitness landscapes, I thought we would have been able to support Evolution agains't ID even without this. I would like to say though, that Evolution shouldn't have to explain the large diversity of life on Earth... I think this planet is made to support large numbers of diverse organisms.
It is only the presence of "Man" that is selectively reducing the numbers and kinds of organisms.

If we ("man") leaves, nature will fill in the niches by itself.

ID has been proven, legally, to be a religious theory. Let's get it out of Scientific debate.

Henry J · 13 February 2007

Re "Little things have fewer genes,"

Nope - some microbes have far more genes than we do.

Re "Large populations (and Large Organisms carrying more neutral mutations) are more likely to survive Selective Pressure."

Having lots of variation across the species is (I gather) what makes that species more adaptable than one with less variety. It isn't the just a large number of individuals, but a larger population is more likely to have a larger variety. Neutral mutations provide variety without directly affecting success in the current environment; if conditions change there's always a chance that some of the varieties will gain an edge over their relatives.

Henry

Sir_Toejam · 13 February 2007

*sigh*

I wish Pim wouldn't keep abandoning these threads right when the comments start getting interesting.

I still see a wide open debate on topic here that has yet to even progress beyond the opening salvos, let alone to any satisfactory resolution.

oh well.

PvM · 15 February 2007

I wish Pim wouldn't keep abandoning these threads right when the comments start getting interesting.

And interrupt my vacation in Spain? No Way

The degenerate code could well be a product of such selection, but: a) there's at least two other competing families of hypotheses for its origin, namely stereochemical and biosynthetic; and b) that code went to fixation a couple billion years ago in most organisms, so I don't see that it could provide much evidence for neutrality selection in modern organisms.

Perhaps they are not all alternative hypotheses to the origin and evolution of the genetic code. I am not sure what you mean by 'neutrality selection' in modern organisms. The existence of significant redundancy in the DNA code confers significant advantages in the area of both robustness to mutation as well as to evolvability. How did evolvability via neutraly arise? The fact that it is itself selectable may be one explanation. Of course, in the end it does not matter if it was chance or selection that has made the genetic code degenerate. What does matter is the impact of this evolvability. More when I get back

Anton Mates · 16 February 2007

Perhaps they are not all alternative hypotheses to the origin and evolution of the genetic code.
— PvM

Certainly they're not exclusive. But since those alternatives do exist, I think it's premature to conclude that genetic code degeneracy developed for the sake of neutrality.

I am not sure what you mean by 'neutrality selection' in modern organisms.

Simply what you said: "Neutrality is a selectable feature since it can improve evolvability." That may not be the case today, simply because there may not be any neutrality-impacting but otherwise...er...neutral alleles to be selected for. Mutations that alter the genetic code are almost certainly lethal in modern organisms, so far as I know. (Not that I've looked into this in detail.)

Sir_Toejam · 16 February 2007

Mutations that alter the genetic code are almost certainly lethal in modern organisms, so far as I know. (Not that I've looked into this in detail.)

I keep thinking about mutations that could alter linkages. I.e., one trait might be genetically linked to another, but a mutation might break that linkage, not be lethal, and allow for the two traits to track a given fitness space independently. I still would consider the mutation that breaks the linkage to be "neutral" in and of itself, even if the resulting unlinked traits might be then able to respond quicker or more completely to the effects of any given selective pressure.

PvM · 18 February 2007

Certainly they're not exclusive. But since those alternatives do exist, I think it's premature to conclude that genetic code degeneracy developed for the sake of neutrality.

I am not sure if that is what I argued. I stated that neutrality is a selectable feature and that neutrality is required for self adaptation. If another process led to degeneracy of the genetic code, we still have the fact that neutrality is required for self adaptation.

Simply what you said: "Neutrality is a selectable feature since it can improve evolvability." That may not be the case today, simply because there may not be any neutrality-impacting but otherwise...er...neutral alleles to be selected for. Mutations that alter the genetic code are almost certainly lethal in modern organisms, so far as I know. (Not that I've looked into this in detail.)

Then again, I did not argue necessarily that such a selection was still taking place. Mutations that alter genetic codes are certainly rare although not non existant. There are also other ways such as codon bias. For instance there are 9 triplets that code for Arganine. The triplet CGA has a 4/9 chance that a single mutation is neutral, while AGA has a probability of 2/9. HIV sequences have been shown to exhibit different biases depending on the location in the genome. Knight, Landsweber, Freeland all have excellent papers on this issue. Other sources Evolving code Wiki Knight's Evolution of the genetic code website Standard Genetic Code Non standard codes

Non-standard genetic codes are, quite simply, genetic codes in which one or more codons have a different amino acid assignment from that found in the standard genetic code. The issue of exactly how codons can become reassigned ("codon reassignment") remains controversial), but the fact remains that it has happened. The diversity of non-standard genetic codes found int he modern biosphere has been well reviewed by Knight et al (Knight 2001). In this review, Knight et al. provided the figure shown below, which collates the phylogeny of all the known non-standard genetic codes. The tree illustrates three general features of the non-standard genetic codes.

Neutrality a necessity for Self Adaptation: Toussaint M. Toussaint (2003): On the evolution of phenotypic exploration distributions . Foundations of Genetic Algorithms 7 (FOGA 2003), Eds: Ken De Jong et al., Morgan Kaufmann, 169-182. [order the book ISBN 0-1220-8155-2]

Abstract. In nature, phenotypic variability is highly structured with respect to correlations between different phenotypic traits. In this paper we argue that this structuredness can be understood as the outcome of an adaptive process of phenotypic exploration distributions, similar to the adaptation of the search distribution in heuristic search schemes or Estimation-of-Distribution Algorithms. The key ingredient of this process is a non-trivial genotype-phenotype mapping: We rigorously define non-triviality, in which case neutral traits (as a generalization of strategy parameters) influence phenotype evolution by determining exploration distributions. Our main result is the description of the evolution of exploration distributions themselves in terms of an ordinary evolution equation. Accordingly, the "fitness" of an exploration distribution is proportional to its similarity (in the sense of the Kullback-Leibler divergence) to the fitness distribution over phenotype space. Hence, exploration distributions evolve such that dependencies and correlations between phenotypic variables in selection are naturally adopted by the way evolution explores phenotype space.

Anton Mates · 24 February 2007

I.e., one trait might be genetically linked to another, but a mutation might break that linkage, not be lethal, and allow for the two traits to track a given fitness space independently.
— Sir_Toejam

Hm. Seems to me that gene duplications would often qualify as such. I wonder if there have been any studies on, say, fluctuations in the gene duplication rate of a lineage experiencing various amounts of parasitism, inbreeding, etc.