Goldschmidt called this a change in “reaction pattern.”
Anthropologist Gregory Bateson (1904-1980) later saw this in terms of a change in genome context. So there can be the conventional mutations that can change individual genes (and be manifest as such), and other mutations that can build up (without external manifestation) until they cumulatively change the “reaction pattern” of a chromosome or set of chromosomes. To distinguish the latter from individual micromutations Goldschmidt called them macromutations. Until manifest in a change in phenotype, these macromutations are invisible.

So people are mixing up Goldschmidt and de Vries. Goldschmidt’s ideas have roots in ideas William Bateson (Gregory’s dad) was enunciating in the early decades of the 20th century. People tend wrongly to conflate William Bateson and de Vries, and hence create even more problems. More on this may be found in our new biography of William Bateson, due to be released by Springer (New York) in April (see: http://post.queensu.ca/~forsdyke/book04.htm)

I should perhaps begin by noting that, although Coyne and I shared, at different times, the same graduate adviser, Coyne was and is a geneticist, while I was and am a herpetologist. Thus my views, and the overlap between them and Coyne’s, do not stem from some shared disciplinary chauvinism, or over-commitment to the centrality of genetics. (I don’t think Coyne’s do either, as some commenters seem to suggest, but it’s harder to make the case that a non-geneticist is too much devoted to genetics.)

Coyne makes two of the chief (and traditional) criticisms of hopeful monsters: mutations of large effect are usually accompanied by deleterious pleiotropic effects, which would make such mutations selected against; and the existence of a simple genetic basis for a trait does not mean that the evolution of the trait was correspondingly simple. The first point is universally acknowledged, at least at some level, which is why even proponents of hopeful monsters suppose their occurrence to be rare. As regards the latter, let me give an example not used by Coyne. One of the earlier-known homeotic mutants in Drosophila converts the halteres into wings. But this does not mean that halteres (or wings!) arose via a single mutation; rather, the gene switches on (or off, depending on your point of view) parts or all of a developmental process. The origin of the trait is the origin of the developmental process, not the switch. To give another example, Sewall Wright studied a condition in guinea pigs called otocephaly which, in its most extreme form, results in the affected guinea pig lacking eyes. The condition has a relatively simple (but not single gene) genetic basis. But the mammalian eye did not evolve in one or two steps on this genetic basis, and there is a long series of eyes with varying features in extant chordates (as well as some relatively recently found and tantalizing fossils) which provide a firmer basis for inferring the history of eyes. That current mutational effect does NOT equal evolutionary origin is by now so well known, that to argue that it does is a fallacy worthy of its own name- and Coyne calls it the ‘macromutationist fallacy’.

There are at least two other traditional criticisms of macromutation that Coyne does not fully address. The first is that evolution is a populational process- in diploid sexual species, individuals with mutations must find mates with whom to pass their new traits on to the next generation. While a macromutation does not necessarily debar an individual from finding, attracting, and successfully mating with another individual, it might make it more difficult, and the greater the phenotypic effect of the mutation, the greater the difficulty. Thus hopeful monsters need to be worried not just about surviving the deleterious effects, they also have to worry about finding a mate. (In plants with vegetative reproduction, polypoidy, which seems the closest thing genetically to Goldschmidt’s systemic mutations, does occur much more commonly than it does in animals.)

The second concerns the relationship between the organism and its environment. Macromutationism supposes that structure precedes function- an individual finds it has some drastically restructured body, and it must find a place it can live. The famous herpetologist G.K. Noble was a mutationist, and supposed that the expanded toe tips of tree frogs arose mutationally, and that the frogs then had to find their way into the trees. This is the flip side of naive versions of adaptationism- the environment poses problems, which the organism must solve by evolving adaptations. Under macromutationism, an organism finds it has a solution, and then must look around for an environment that poses the problem it just happens to have the solution to.

Let’s take the evolution of whales as a not entirely arbitrary example. Under naive adaptationism, some early artiodactyls are pitched out to sea, and must evolve flippers, tail flukes, etc. to solve the hydrodynamic problems of locomotion. Under macromutationism, some poor, hopeful artiodactyl is born on land with flippers, tail flukes, etc., and must find its way to water (and also hope there’s another hopeful artiodactyl out there to mate with). But neither of these views seems right. The organism’s environment is not purely imposed by external circumstances, but arises as a complex interaction between the organism’s structures and behaviors, and environmental characteristics (R.C. Lewontin likes to say, perhaps overstating a bit, that organisms create their environments). Structure and function are intertwined.

For whales, we in fact know from fossil evidence that they evolved through a long series of intermediate morphologies and ecologies, and not via a hopeful monster. There are, indeed, in mammals, teratological flipper-like limbs that occur in normally-legged species. But that’s not how whales got flippers. Nor, probably, did seals, manatees, etc., although the fossil record is not so compelling for these groups. The living sea otter provides us with an example of a step in the origin of flippers from feet, and shows the corresponding function/ecology.

Perhaps the best argument against hopeful monsters is that we have, at least in vertebrates, many fossil sequences documenting the origin of higher taxa via numerous intermediate steps. We have long known that tetrapods evolved from lobe-finned fishes. The discovery of fossils near the transition such as Panderichthys ,and the very recent discovery by Neil Shubin, Ted Daeschler and Farish Jenkins of Tiktaalik, is filling in the structural differences between fish and amphibian, so that we can see exactly how legs gradually arose from fins. The fossil record is a far cry from Richard Goldschmidt’s notion that simple changes in thyroid hormone levels might turn a fin into a foot in a single step. Another excellent example is the transition between reptiles and mammals. As long ago as the 19th century the herpetologist E.D. Cope identified early synapsids as the closest relatives of mammals. At the time, it could be asked (and is asked to this day by creationists who either don’t know or deliberately ignore the fossil record), “how could reptilian jaw bones become mammalian ear bones?” A macromutation (or a miracle) might have seemed a plausible answer, but in fact we now know, thanks to the work of Fuzz Crompton, Farish Jenkins, and many others, more or less exactly how this occurred- by many steps, over millions of years.

Metameric (segmentally repeated) structures allow production of whole new segments without great alteration of the developmental machinery, and this might allow changes that could perhaps be described as macromutational (although arguably not; and variation in plate number in sticklebacks, although extremely interesting, would be rather small consolation to Goldschmidt). In vertebrates, though, although vertebral number has varied considerably (along with the corresponding segmented muscles, nerves, blood vessels, etc.), limb number, despite occasional teratological variation, has never varied from four, except for losses of limbs, which in all well known cases have been by gradual reduction (e.g. lizards, whales).

The take home lesson of vertebrate paleontology and comparative morphology is that much of evolution is the gradual adaptive modification of pre-existing structures and their underlying developmental programs.

One specific example of Judson’s that Coyne addressed from a genetic point of view that I would like to address form a comparative morphological point of view is cephalic baldness in chickens and vultures. Judson supposes the first indicates how the latter arose, but admits to not knowing for sure. My first thought, as someone who has actually measured birds’s heads (I’ve dabbled in ornithology), is that exactly how much feathering there is on a bird’s head varies considerably within and among species. A few minutes reflection and checking some pictures confirmed that there is a wide range of nakedness of the head. Caracaras lack feathers around the eyes and cheeks, picathartes are bald to about the middle of their heads, guinea fowl are mostly naked but have lines of feathers running up the neck and head, and vultures are bald on head and neck. A real ornithologist could probably provide more examples. Now the examples I give do not form a phylogenetic series, but like many of Darwin’s arguments, they provide a “how possibly” argument for how baldness can arise gradually. As for Darwin, such arguments are an effective response to the “argument from personally incredulity” (which is not what Judson used; but it does exclude accepting macromutation in default of any alternative). Thus study of comparative feathering does not cry out for a macromutational origin of baldness.

Disregarding briefly The Monkey Man’s sage advice, let me briefly address two specific criticisms of Coyne. One is that Coyne is following a discredited Lyellian view of geology. If Coyne mentioned geology, I missed it. I will mention though that our modern theory of the earth, plate tectonics, would have made Charles Lyell quite happy, because it provides not only for uniformity of process, but uniformity of state- the cycling of continental agglomeration and splitting over hundreds of millions (if not billions) of years would fit nicely in his view of the earth in dynamic equilibrium. This uniformity of state is something which, as Lyell finally admitted, eluded him for the condition of life on earth. The other is that Coyne disregards Darwin’s lessons on the importance of the study of variation under domestication. Quite the contrary, Coyne’s points are precisely Darwinian. Darwin used artificial selection and variation under domestication as vera causae for the power of cumulative selection of variations; Darwin did not think the particular variations under domestication especially germane. Indeed, the reason Darwin, unlike Wallace, used arguments about domesticated forms is because Darwin saw that the domesticated breeds would usually be at a disadvantage in nature, and that selection would quickly revert them to “wild type”. Wallace saw this reversion as indicating changes under domestication were unstable, rather than the result of changed selection pressures as Darwin did.

Finally, I note that creationists are already here in the comments touting macromutation as showing creationism is correct. This has more to do with the ignorance of creationists than anything Coyne’s critics have said. The ability of creationists to misconstrue the views of evolutionists is legendary- P.Z. Myers has noted a debate with a creationist in which the creationist insisted S.J. Gould didn’t believe in evolution, but rather punctuated equilibrium!

Another error is that some say classical darwinian selection rules for evolution within smaller clades (microevolution, for instance), but that saltationism is needed to explain the differences between higher taxonomic orders. This is not true, you are simply more different if you share a more remote common ancestor. Prud’Homme et al 2006 (PNAS) find developmental mechanisms affect both macro and microevolution in basically the same way: Both reveal “regulatory regions” that constrain evolution. “Saltation” was as important when big clades diverged eons ago (when they were the newest “branchtips”) as it is nowadays in ongoing processes of evolution and speciation.

On the phenotype side we know that there have also been dramatic changes. Does anybody think that the incorporation of mitochondria to make eurcayotes happended one base pair at time?

No, but it is overwhelmingly likely that it happened by smaller steps from facultative to obligate endosymbiosis, including loss of mitochondrial genes or their transfer to the nucleus in smaller chunks. Unless you have some reason to assume that it was nothing like the endosymbionts where we can observe “evolution in action” today.

“Unfortunately, the hype about hopeful monsters is not deserved, because there are several errors in inference made in this piece. First, just because a mutation has a big effect WITHIN a species does not by any means imply that difference between species in the same trait are due to that mutation. There are mutations in humans causing dwarfism, for example, but it

If he had merely addressed the weaknesses in Dr. Judson’s piece, which are significant, then we’d have a valuable contribution from a heavyweight. Instead, he pulled out a grenade, and the mess he made is, in part, yours to clean up.

In his frenzied assault on unwarranted extrapolation, I wager he’s done damage to experimental evolutionary biology of every kind, but I couldn’t help but wonder whether he thinks that studies of Drosophila genetics can tell us anything about the evolution of anything other than Drosophila. His paragraph on the difficulty of understanding the past gave the impression that he would exercise care in addressing controversies in evolutionary biology. What followed was overwhelming evidence to the contrary.

What I found particularly disgusting was the cavalier dismissal of studies of domestication. (Paging Mr. Darwin. Mr. Darwin?) Exactly what is different about selection at the hands of humans, vs. selection influenced by, say, fruit flies? And I laughed out loud when he dismissed corn because it “would never thrive in nature because the seeds don’t disperse.” Wait, a plant that depends on an animal for reproduction?! Stop the presses! I wonder if there are any plants that depend on FRUIT FLIES for seed dispersal or pollination…

I’m sure that the debris from Coyne’s grenade will soon be providing a feast for the anti-evolution vultures that dog his field. But that’s not why his rant pissed me off. He’s a brilliant scientist, and his Cassandra syndrome is understandable given the prominence of evo-devo ideas. His voice is too important to ignore, and that means he has to be more careful than this.

In a paper by Gene Hunt in the Proceedings of the National Academy of Sciences, he reports on a study of the fossil record for statistical occurrences of three evolutionary models: directional change, random walk, and stasis. (“The relative importance of directional change, random walks, and stasis in the evolution of fossil lineages” http://www.pnas.org/cgi/content/abstract/104/47/18404) Hunt examined evolving traits and reports the following:

“Evolution in these traits was rarely directional; in only 5% of fossil sequences was directional evolution the most strongly supported of the three modes of change. The remaining 95% of sequences were divided nearly equally between random walks and stasis.”

The fossil record does not support gradualism. That concern goes all the way back to Darwin. The dogma of gradualism is so fiercely defended because any alternative would give comfort to creationists. But why not go to where the data leads? Isn’t that the way science is supposed to work? The creationist model is a better fit of the empirical data than Darwinian gradualism. Science needs to acknowledge that and move on.

Now, admittedly, I’m more of an embryo and fossil kind of guy. I am NO expert on the genetics of adaptation. Yet, it is unavoidable to notice statements like this from Orr Nature Reviews in Genetics 2005 (6: 119)

“Early empiricists, including Theodosius Dobzhansky, Hermann J. Muller, Kenneth Mather and Julian Huxley, claimed that there was considerable empirical support for micromutationism. For example,Huxley argued that

One comment cited melanism as an example of a trait controlled by a few genes of major effect. The key is that several genes have been implicated in melanism, not just one. Goldschmidt insisted that new lineages arose from major saltations caused by a single gene of large effect because he believed that gradual changes couldn’t connect microevolution to macroevolution. But do we have evidence for just one mutation causing a new adaptation distinguishing two species?

This question can only really be addressed is with proper genetic data about adaptations within species and among species, which I’m willing to say we don’t have enough of yet. (Enter Coyne’s comment about needing to do genetics to discover genes for adaptations). The more we know about the genetic basis of traits, the better we’ll be able to adjudicate the relative importance of gradualism and saltationism.

Get yourself a blog, now!

My only advice would be not to get caught up in every potential argument from those posting afterwards, as every single element of your article will find disagreement with someone.

Isn’t Gould Mr. Hedge-his-bets-backtrack-and-say-everything? What I’ve read of him, he comes across as a person who, if discussing the question of whether or not black is white, would say “Black is completely different from white, but really they’re the same and it’s only a matter of difference in degree between, but in fact they’re identical and they’re also the same as 65,533 shades of grey in between, each of which are completely distinct from each other and black and white.” I note others (e.g. Steven Pinker) have commented on this tendency of his.

In this instance, Coyne plays the bull. The issue of macromutations has a status with some evolutionary biologists akin to High Dogma, and they rush to attack any heresies in this direction. This process started as soon as evolutionary biology itself – Darwin was influenced by Lyell’s revolution in geology that tiny incremental changes over eons could literally move mountains. In that era dramatic change was equated with creationism, or more broadly with missing the fundamental point that evolution could accumulate tiny changes and achieve big results.

More recently it has become clear that Lyell was wrong – specifically that a strictly incremental and slow version of geology is wrong. Dramatic catastrophes can play a role in landforms – often they play the dominant role.

Within biology the matter of macromutation continues to resurface repeatedly – as Coyne points out. Coyne clearly believes that the idea has no merit – which is fine, he is entitled to his opinion.

But he goes way overboard when he accuses Judson of being irresponsible. The fact is that very smart people do reexamine the idea periodically. It is ridiculous to suggest that Judson is “irresponsible” for airing this debate.

Indeed the very fact that Coyne goes on say that the idea comes up time and again, or that some of Judson’s points are “common in the evo devo community” refutes the notion that it should be off limits. Regardless of whether you consider Judson a scientist or a journalist, there is nothing irresponsible here.

Coyne is a partisan of one side in an ongoing debate, and he doesn’t like it that the other side has gotten some press.

Coyne may be right (or not, see below), but it is hardly irresponsible to suggest that he isn’t.

Judson concludes by saying that there is only a “suggestion” that hopeful monsters have some valid basis. She is more than entitled to express her opinion without Coyne getting high and mighty.

That is mostly about his tone. However, I suspect that Coyne and his camp also wrong on the facts. Judson does not make the following points, but they are further suggestion that some aspects of macromutation MIGHT play a role in evolution. I will briefly list a couple.

There are two separate kinds of “macromutation” one can talk about. One is a large change in the genotype. The other is a large change in the phenotype. The two may or may not be correlated – one can imagine a huge dramatic shift in the geneome that has no corresponding change in the phenotype. Or a big change in the phenotype that was caused by a single base pair change. Each deserve to be considered as a macromutation of a sort.

On the genome side we know that individual genes are duplicated – that is clearly a huge change. The most dramatic form of this is whole geneome duplication, which we know has occured muliptle times in evolutionary history.

That can’t have happened one base pair at a time – instead some copying error duplicated large stretches of the geneome, or all of it. That surely qualifies as a macromutation at the genomic level. There may (or may not) have been a correspondingly large change in the phenotype but that is a separate issue.

Other macromutations of the genotype include incorporation of foreign dna, for example via retroviruses and reverse transciptase. Many cases have been documented.

On the phenotype side we know that there have also been dramatic changes. Does anybody think that the incorporation of mitochondria to make eurcayotes happended one base pair at time? No, the current theory is wholesale adoption of a foreign organism, likely enabled by some genetic mutations in the host cell.

Work with knock-out animals, RNAI and gene splicing have shown that changing single genes, or even groups of genes, very dramatically can sometimes have no effect and sometimse have a big effect.

These cases are only suggestive – but that is the point here. I agree with Coyne that ultimately genomic research will figure this out. Until that research is done and the answer is in definitively it is worth discussing.

More generally the view of the micromutation crowd, ranging from Fisher to Coyne is that macromutations are unlikey to survive. This is the great and glaring unproven hypothesis – almost a religious point – with this camp

This is a quantitative issue, yet Coyne and others hand wave it away with no proof. They assert that “most” macromutations are harmful and could not survive (or could only in a greenhouse with human help).

How do they know?

The point here is one of competing rates – or probabilities – of very rare events.

First, we don’t have any good way to measure the likelihood of survival of an animal with a macromutation (of either genotype or phenotype). Second, we don’t know how often these macromutations occur. Without knowing those rates (which can depend on context and environment etc), how can Coyne be so dogmatic?

Even if the rate of survival is very low, nature is rolling the dice a lot of times. Even a miniscule probability of success will occur if you do sufficiently many trials. One in a billion tries is actually a high probability here – becuase nature has had way more than a billion trials. Indeed one can imagine situations where probabilities like one part in 10^20 or even lower could be important.

Fisher should have known this, but in his day they held incorrect views of the genome and its fragility to mutation. We know better now – small mutations can have big impact on the phenotype, and big mutations can have none.

Coyne accuses Judson of logical errors – his error is that he provides no proof for the assertion that macromutation must always have such a low probability of survival that it can’t have played a role in evolution. It is a ridiculous position to take.

Ancedotal observation of a few sick bald chickens (an example he uses) do not count against this quantitative issue.

I am not aware of vulture development to know whether their headfeathers grow at first, are stunted, fall out, or progressively fall out as they feed on carcasses.

The flounder is an interesting issue. An eye progressing towards the (new) dorsum is of no advantage until it ’rounds the corner’. Whence comes the selection pressure for this gradual movement?

I once heard this expressed this way: At a table full of scientists and scientist types (groupies?), someone quoted Ptolemy (perhaps apocryphally; I can’t find it anywhere):

“The goal of science is finding the most compelling story consistent with the facts.”

Someone else at the table said,

“No! It is finding the simplest story consistent with the facts.”

Betwixt lies all sorts of room for disagreement, including, it seems, this one. I’m not saying both Coyne and Judson are consistent with the facts on this one. (I’m no qualified judge, but Coyne convinces me Judson wandered astray.) But you see that tension here — and elsewhere, constantly. In the pivotal 19th-century argument over evolution, for instance, which pitted two beautiful, compelling narratives against one another: Louis Agassiz’s creationist yarn, which was a gorgeous narrative, and Charles Darwin’s story of evolution by natural selection, which also had a great narrative drive (if no teleological ‘motive’) and a compelling aesthetic unity. Darwin’s won out, of course (well, mostly …) because he proved his more consistent with the facts.

But the same tension was at play. We find attractive narrative explanations that are simple — but not TOO simple. And we like NOVEL things (or apparently novel things). This affects both scientists and scientific journalists. I would say, by the way, that sci journalists, just like others, DO have an obligation to describe a field accurately. Doesn’t mean they can’t go out on a limb with their own opinion or reading of something, though, as long as they make clear that — and not reporting — is what they’re doing. This has its dangers, of course, which Judson has encountered in Coyne’s post.

Thanks to Coyne for writing this and Carl for putting it up there.

David Dobbs
Contributor, NY Times Magazine and others
blog at Smooth Pebbles

As a paleobiologist, I myself have in mind several lineages in the evolution of life that show changes such as homeotic transformations, hometic frameshifts, and other that are clearly qualitative, not fitting any gradualistic story. So my mind is pretty much made up, and I sort of smile at the “demonization” of saltationism.

I think the datum of the naked necks of african chickens mentioned by Greg laden clears up THAT case pretty well. This whole thing about the “horrific side effects” put forward by gradualists is always very speculative and adaptationist, based on mere correlations but rarely any actual mechanism. The naked neck of vultures being the result of a single mutation is a completely plausible hypothesis.

Those african chickens are probably one more of several documented cases of big differences in WILD populations. Usually it is a matter of a single or a few alleles; such as the melanism in Biston, for instance. This was no fading of several genes with small effect going to grey then black. It was….well, a MUTANT. With a DRASTIC effect on pigmentation.

The whole domestic vs wild argument of Mr. Coyne is completely unconvincing.

I would very much like to know what case would Mr. Coyne consider the best case study of the microevolutionary origin of an adaptation by gradual accumulation of several genes. Allen Orr, another expert on the genetics of adaptation, thinks that the documentation for this is lacking, whereas cases of single or few genes with large effects are much more common.

“The issue remains alive because evolution is a historical science.”

“But you can’t blithely extrapolate from rare large-effect mutations within species [...]”

You can indeed blithely extrapolate when speaking in “may well be” mode – in other words, while brainstorming hypotheses. Dr Judson expressed considerable uncertainty about whether a single saltation actually denuded the vulture’s head.

I guess the vulture idea may not contribute very much support to Dr Judson’s suggestion that the hopeful monster doctrine is currently resurgent, since it’s merely an idea, by Dr Judson’s own admission. But at least she was clear about it being just an idea.

Overall, Dr Judson’s essay seems to be quite far from suggesting that the existence of any mutant phenotype in any taxon proves, or strongly implies, that any similar phenotype that’s fixed in any other taxon must have arisen as a saltation. Whereas Dr Coyne’s essay, perhaps mostly by accident, seems overall to incorrectly attribute to Judson this position – a position which I don’t think anyone would want to be associated with.

More importantly, it seems Dr Coyne may have refuted Judson’s understanding of the ultrabithorax and sex comb stuff. Assuming so, I’m glad that was pointed out, and am grateful for Dr Coyne’s piece.

The original incarnation of punctuated equilibriumwas made more than just a claim of rapid allopatric speciation. The theory explicitly invoked instantaneous macromutational change. Here is a quote from Gould (1980, Paleobiology 6:119):

“I envisage a potential saltational origin for the essential features of key adaptations. Why may we not imagine that gill arch bones of an ancestral agnathan moved forward in one step to surround the mouth and form proto-jaws.”

To me, this seems like a pretty big saltational change! Gould and Eldrdge later backed off on this, saying that “Opponents now accept that punctuated equilibrium was never meant as a saltational theory . . ” (Gould and Eldredge Nature 366:326).

I am not sure to whom this response is intended — if it is intended to answer my call for Jerry Coyne to display the same responsibility he calls for in others, I am afraid it falls quite short, for it offers little to justify the spirit of statements such as:

After getting a severe drubbing from geneticists…

(and that is one example).

To address the text from Coyne quoted above, note that Gould writes:

Why may we not imagine that gill arch bones of an ancestral agnathan moved forward in one step …

It is also worthy of note that Gould’s text above [unintentionally] anticipates Coyne’s demands for burden of proof i.e., who can blithely claim what.

That Gould can “envisage a potential saltational origin” does not commit “punctuated equilibrium” to be a “meant as a saltation theory”.

1. Re neil’s comment: I didn’t say that doing genetics was the only way to “investigate the nature of evolution.” Rather, I said that it’s really the only way to find out what GENES were involved in evoutionary change. I can’t think of any other way to do this besides crossing species (impossible between distant relatives) or doing transgenics. If anybody knows another way, I’d be glad to hear it.

Can’t argue with that one!