How do evolutionary novelties arise? The conventional explanation is that the first step is the chance formation of a genetic mutation, which results in a new phenotype, which, if it is favored by selection, may be fixed in a population. No one sensible can seriously argue with this idea—it happens. I'm not going to argue with it at all.

However, there are also additional mechanisms for generating novelties, mechanisms that extend the power of evolutionary biology without contradicting our conventional understanding of it. A paper by A. Richard Palmer in Science describes the evidence for an alternative mode of evolution, genetic assimilation, that can be easily read as a radical, non-Darwinian, and even Lamarckian pattern of evolution (Sennoma at Malice Aforethought has expressed concern about this), but it is nothing of the kind; there is no hocus-pocus, no violation of the Weissmann barrier, no sudden, unexplained leaps of cause-and-effect. Comprehending it only requires a proper appreciation of the importance of environmental influences on development and an understanding that the genome does not constitute a descriptive program of the organism.

Background

We know intuitively that the latter is not the case. We can see that any time we look at a developmental mistake: biology is plastic, and tries to accommodate errors, even gross errors, and assemble a functional organism. For instance, it is fairly easy in the lab to induce two-headed organisms (and they happen spontaneously in the natural world often enough). This is obviously a radical change! As one class of problems, think of the plumbing: a single heart needs to supply blood to two brains, and the aorta has to sprout a series of carotid arteries. And it does. Muscles, nerves, guts, respiratory pathways…all have to reorganize themselves in a sensible way in the absence of any central genetic program specifically evolved to cope with such a surprising phenomenon. Development is a process that tries to respond in a constructive way to a series of inputs, and what comes out tends to have a functional logic to it.

This capability of the organism to respond developmentally to changes in its environment allows us to think in a different way about how novelties arise. Instead of appearing first as a genetic change in an individual ("genotype precedes phenotype" evolution), a new morphology may be a consequence first of a consistent response to a common environmental condition which is only later reinforced by the evolution of genetic causes (note: the genetic causes do not arise as a direct result of the environmentally induced condition, but instead the condition makes mutations that support it more favored by selection; this is not Lamarckism!). This is "phenotype precedes genotype" evolution.

The idea may feel counterintuitive to those of us steeped in the genecentric tradition of modern biology, but trust me, it has substantial popularity in the evo-devo crowd. It's a central theme of Mary Jane West-Eberhard's excellent Developmental Plasticity and Evolution, a book I can't recommend highly enough to anyone who wants to get into the details (it's not a book for casual readers, unfortunately—it's fairly dense and technical). There are a number of terms that are used liberally when discussing the concept, so I'm going to take some definitions straight from West-Eberhard's book and try to explain how they work.

Phenotypic accommodation: "the immediate adaptive adjustment of the phenotype to the production of a novel trait or trait combinations." My example of the two-headed animal is an example of phenotypic accommodation, as is the two-legged goat effect. Development will remodel morphology to a remarkable degree around almost any perturbation, whether the cause is genetic or environmental. We are very, very good at working around stresses in development. In a sense, that's why development has evolved.

Given that we can respond to variations in the environment with variations in the pattern of development, we then have the ability to acquire morphological innovations with no specific genetic cause at all. These cannot have any direct, long-term evolutionary effect in the classic sense, of course, because they aren't passed on to offspring (although we do often pass on our environment to our offspring...but let's not think about that right now. There are some possibilities for really radical evolutionary theories here.) What they can do is allow an organism to thrive in an environment which selects for new heritable traits, a phenomenon called the Baldwin Effect: "the idea that phenotypic accommodations to variable or extreme conditions can affect the direction of genetic evolution under natural selection, permitting survival in an unusual environment and allowing time for selection to favor adaptation to it." This is a key idea behind "phenotype precedes genotype" evolution. (Social Learning and the Baldwin Effect, by David Papineau, is a good online source if you want to learn more about the effect.)

The end result of all this, the part that brings this mode of evolution into full compatibility with neo-Darwinian ideas, is genetic assimilation: "a process by which a phenotypic character, which initially is produced only in response to some environmental influence, becomes, through a process of selection, taken over by the genotype, so that it is found even in the absence of the environmental influence which had at first been necessary." Where canalization refers specifically to increasing constraints on a developmental pathway, genetic assimilation is a broader term that refers to the acquisition of a genetic mechanism to support any developmental outcome; we could imagine assimilation of a genetic factor that widens flexibility, for instance.

A related concept is canalization: "an evolved reduction in developmental flexibility that renders the development of an adaptive phenotype resistant to environmental and genetic (e.g., mutational) perturbations that would produce deviations from optimal form." This is an idea advanced by Waddington. If a particular organismal morphology is particularly successful, mutations that make it robust and resistant to change would be advantageous; canalization is a conservative process that would oppose evolutionary change. One of the biases inherent in with working with many lab animals, such as Drosophila or the zebrafish, is that we suspect that development in these fast-growing model systems is highly canalized, i.e. relatively rigid and very strongly determined. Focusing on these organisms gives us an underestimate of the range of variation present in the development of less tightly constrained species.

There lies a problem. Demonstrating the details of the influence of the environment on the organism has been somewhat elusive, since lab animals have been chosen for the property of minimizing such influences, and most lab research involves reducing variables by reducing environmental variation. Expressing an adaptive trait in response to environmental influences exclusively should also be a transient feature in the evolution of a species, perhaps found only in localized populations.

Symmetry breaking

I hope that overview convinces everyone that there is nothing unreasonable or heretical about genetic assimilation, and that there is no obstacle in principle to it occurring. The only question here is whether it is a significant factor in evolution, and that is where Palmer's paper comes in: he argues that we can see evidence of genetic assimilation in the evolution of a rather important feature in evolution, bilateral asymmetry.

A hallmark of the Bilaterians, like us and flatworms and fish and cows, is bilateral symmetry: we have left and right halves that are at least superficially mirror images of one another. However, underlying that is a secondary asymmetry. Our hearts are lopsided because one half has a harder job to do than the other; our livers are mostly on one side of our body; and some organisms, such as snails, have a characteristic handedness to their spiral form.

However, emerging from this diversity are two fundamentally different, yet easily distinguished, types: antisymmetry, in which dextral and sinistral forms are equally common within a species, and directional asymmetry, in which most individuals are asymmetrical in the same direction. These two asymmetry types differ in an important way. In antisymmetric species, direction of asymmetry is almost never inherited, whereas in directionally asymmetric species, it typically is.

Antisymmetry is the key case. There are organisms that exhibit bilateral asymmetries which are not determined genetically; different individuals have right- or left-handed organs, and the parental pattern is not passed on to their progeny. One of the things the paper does is catalog fossil and extant species that exhibit antisymmetry and ask how often a period lacking genetic control precedes the establishment of a fixed handedness, a situation illustrated diagrammatically below.

Two evolutionary routes to directional asymmetry. (Route a) Conventional evolution (genotype precedes phenotype). Initially, a mutation induces asymmetry in a particular direction. Before fixation, two phenotypes coexist: symmetric and dextral or symmetric and sinistral. (Route b) Genetic assimilation (phenotype precedes genotype). Initially, a mutation induces asymmetry without directional bias. Before fixation, three phenotypes coexist: dextral and sinistral (individuals carrying the mutation) and symmetric (individuals lacking the mutation). Upon fixation, dextral and sinistral phenotypes persist in equal frequencies (antisymmetry). Along the second (right) leg of route b, an additional mutation arises that biases asymmetry in one direction. Before fixation, dextral and sinistral phenotypes coexist but one is more abundant (e.g., for a dominant dextral mutation, dextral individuals include antisymmetric and dextral genotypes, whereas sinistral individuals represent only the antisymmetric genotype). The second leg of route b corresponds to genetic assimilation because a conspicuous phenotype (e.g., dextral) that is not heritable is replaced evolutionarily by one that is. Notably, if no antisymmetric species occur within a clade, either living or as fossils, then genetic assimilation cannot be inferred. Such evolutionarily ephemeral, undetected antisymmetry yields "ghosts of genetic assimilation past" and may be much more common than currently believed. Numbers outside parentheses include only reliably inferred phylogenetic transitions; numbers inside parentheses include all inferred transitions regardless of reliability.

What he found was that roughly half the time, evolution has followed route b, with no sign of tight genetic control at first, followed by a more consistent handedness, indicating that genetic assimilation had occurred. The other half, route a, directional asymmetry is always present. However, genetic assimilation is going to be typically undercounted for reasons I've already mentioned, so occurrence in half of the cases is almost certainly going to be an underestimate.

Another analysis carried out in the paper is an examination of the molecular pathways behind known chordate asymmetries. There is an array of genes that are activated asymmetrically in the development of the heart, for instance, a pathway called the nodal signalling cascade. There are four highly conserved genes, Nodal, Lefty1, Lefty2, and Pitx2, that seem to be universal in function in the vertebrate lineage; you can think of them as the heart of the heart pathway. The curious thing, though, is that the genes that precede the nodal pathway vary in different animals, and also, there are many non-conserved genes downstream of nodal. While the core module is the same, it is activated in different ways and has divergent effects!

Genes expressed or functioning asymmetrically during early development. Each colored column applies to one taxon. Each row applies to a single gene or trait. Colored entries indicate asymmetrical expression or function as indicated in column 2. Noncolored entries mean expression or function differed from that indicated in column 2. Gene order from bottom to top parallels temporal order of expression as closely as possible. LPM, lateral plate mesoderm; sym, symmetrical expression; no expr., no expression; ?, no data or not known; n/a, not applicable; L, left; R, right; perinodal/paraxial, on the periphery of or adjacent to the node or its equivalent in amphibians, fish, and lower deuterostomes; CNS, central nervous system; *, table entry requires clarification or expression order differs from that in the figure.

We've seen this pattern before, as the author notes.

Variation in the nodal cascade among vertebrates, like variation in mechanisms controlling primary axis formation, resembles an hourglass: a short, conserved core in the middle of the signaling pathway, the Nodal-Lefty1-Lefty2-Pitx2 pathway, with divergent elements upstream and downstream. Vertebrate embryos, therefore, appear to pass through a molecular phylotypic stage, a conserved stage that may provide clues about ancestral developmental pathways, during ontogeny, just as they appear to do morphologically.

How interesting and how odd. How could this have happened?

One suggestive observation is that urochordates and cephalochordates have some differences in the core heart genes, and that ascidian larvae have symmetrical hearts, while lancelet asymmetries seem to be the result of an asymmetrical cleavage pattern. The nodal pathway isn't used to generate heart asymmetries at all; instead, it seems to be crucial in defining brain asymmetries. The idea is that the heart initially exhibited antisymmetry, and that the mechanism of genetic assimilation involved the independent recruitment of a core brain pathway to add a layer of genetic control to the process.

I think Palmer has made a good case that at least some fundamental properties arose in evolution as a result of genetic assimilation, and that it ought to be better appreciated as a factor. He concludes by mentioning other examples of the process.

Is genetic assimilation as common among other traits as among biological asymmetries? Regrettably, because compelling evidence is difficult to obtain, rather few natural examples are known. They include (i) the shell shape in freshwater snails, which responds plastically to turbulence in some populations but not others; (ii) viviparity in reptiles, in which some optionally retain eggs in the oviduct and others consistently do so; (iii) sex determination in turtles, in which environmental control is ancestral, but genetic control has evolved six times; (iv) leaf form in buttercups, in which some populations produce aquatic or aerial leaves in response to growth conditions, but others grow only aerial leaves; and (v) antattracting extra-floral nectar secretion in Acacia trees, which occurs only after insect attack in some species but is continuous in derived (obligate ant-hosting) species. Genetic assimilation may be much more widespread than currently believed.

Palmer AR (2004) Symmetry breaking and the evolution of development. Science 306:828-833.