Newman&Müller2010

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Morphological Evolution:Epigenetic MechanismsStuart A Newman, New York Medical College, Valhalla, New York, USA

Gerd B Muller,University of Vienna, Vienna, Austria

Organismal forms have not always been generated by the

highly integrated developmental programmes charac-

teristic of modern multicellular species. Physical forcesand other conditional processes playeda more prominent

role at the earlier stages of evolution, establishing mor-

phological templates that were consolidated by later

genetic change. In particular, with the appearance of

multicellular aggregates, physical effects relevant to

parcels of matter larger than single cells were newly

mobilized by gene products (e.g. the developmental-

genetic toolkit of the animals) that had originally

evolved to serve unicellular functions. These mechanisms

are responsible for continued generation of morpho-

logical novelty, and are ultimately involved in the estab-

lishment of the individualized and heritable constructionunits of morphological evolution known as homologues.

Introduction

Materials of the nonliving world take on forms dictated byexternal forces to which they are susceptible by virtue oftheir inherent physical properties. Water, for example,forms waves and vortices if it is mechanically agitated,

whereas clay bears the record of its most recent physicalimpressions long after they have been exerted. Livingmetazoa multicellular animals seem to obey differentrules: their forms appear to be expressions of intrinsic

developmental programmes. Although organisms must, of

course, exchange energy and matter with the external worldto stay alive, the general architectures andfine details of the

forms they assume are taken to have become independentof the external environment.

But consideration of the mechanisms of morphogenesis

and pattern formation revealed by modern developmentalbiology suggests that at early stages in their evolution theforms of metazoan organisms were not generated in such a

rigid programmatic fashion. Rather, the earliest multi-cellular organisms must have been moulded by theirphysical environments to a much greater extent than con-temporary organisms and, with regard to the generation ofthree-dimensional form, were more like certain materialsofthe nonliving world than are their modern, evolved coun-terparts. See also: Eukaryotes and Multicells: Origin;

Multicellular Organs and OrganismsPresent-day organisms are characterized by redun-

dancies of gene action and highly integrated signallingnetworks which ensure that developmental pathwaysare reliable and resistant to perturbation. In contrast, themost ancient multicellular creatures were simple cellaggregates that arose by adhesion of originally free-livingcells, or by the failure of the same to separate after mitosis.Although the single-celled progenitors were themselves thesophisticated products of a billion years or more of evo-lution, the steps that made them multicellular could havebeen as simple as a single mutation that rendered a cellsurface protein sticky, or even a changein theion content of

the sea that provided a pre-existing protein with this newproperty. Once this occurred, and it probably occurredmore than once in the history of life, living organisms

became susceptible to new sets of determinants: initially theforces that mould what physicists refer to as soft matteralong with the inherent self-organizing capabilities ofchemically and mechanically excitable materials, and laterother conditional form-generating processes, such as tissueinductive interactions. We refer to these conditional, non-programmatic determinants collectively as epigeneticmechanisms (Newman and Mu ller, 2000). Seealso: Beyondthe Genome; Epithelial Branching; Modelling of PlantGrowth and Development; Nonlinear Dynamics andChaos

Keynote article

Article Contents

. Introduction

. Physics of Multicellularity and the Origin of Body Plans

.

Interplayof Genericand Programmatic MechanismsofDevelopment

. Epigenetics of Advanced Development

. Origin of Morphological Homology

Online posting date: 15th February 2010

ELS subject area:Evolution and Diversity of Life

How to cite:

Newman, Stuart A; and Muller, Gerd B (February 2010) MorphologicalEvolution: Epigenetic Mechanisms. In: Encyclopedia of Life Sciences(ELS). John Wiley & Sons, Ltd: Chichester.

DOI: 10.1002/9780470015902.a0002100.pub2

ENCYCLOPEDIA OF LIFE SCIENCES& 2010, John Wiley & Sons, Ltd. www.els.net 1
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Physics of Multicellularity and theOrigin of Body Plans

Multicellular organisms first arose more than 600 Ma. Byapproximately 540 Ma, at the end of the Cambrian

explosion, virtually all the bauplans or body types seen inmodern animals (the Metazoa) already existed (ConwayMorris, 2006) (the complex plants arising later). Althoughthe early world contained many unoccupied niches withinwhich new organismal forms could flourish, this alone canneither account for the rapid profusion of body plans oncemulticellularity was established, nor for the particularforms that bodies and organs assumed. In particular,

metazoan bodies are characterized by axial symmetries andasymmetries, multiple tissue layers, interior cavities, seg-mentation and various combinations of these properties.The organsof these creaturesare organizedin similar ways,on a smaller scale. Just as we recognize that liquids, clays,

taut strings and soap bubbles can take on only limited,characteristic arrays of shapes and configurations, it isreasonable to ask what the characteristic spectrumof formswould have been for ancient multicellular matter. Suchmatter consisted of cells producing numerous gene prod-ucts, some of which were released, and some of whichremained at the surface, providing the means for cellaggregation. The highly integrated genetic mechanisms ofpattern formation and morphogenesis seen in present-dayorganisms could not have been present at the dawn ofmulticellularity. Rather, as will be described, the body andtissue forms we have come to associate with modernmulticellular organisms were already inherent in thematerial make-up of their ancient, less programmedancestors (Newman et al., 2006). See also: AdhesiveSpecificity and the Evolution of Multicellularity; Cam-brian Radiation;Chordate and Vertebrate Body Plans

Adhesion, differential adhesion and corticaltension

The advent of cellcell adhesion early in the history ofmulticellular life opened up possibilities for the mouldingof bodies and their tissues that were unavailable to single-celled organisms. The primary reason for this is that dif-

ferent physical processes predominate at different spatialscales the shapes and forms of macroscopic objects, suchas multicellular aggregates, are influenced by physicaldeterminants different from those that noticeably affectmicroscopic objects, such as individual cells.

Cell adhesion is the defining condition of multi-cellularity. When all the cells in a cluster have the samenumber of adhesion molecules on their surfaces, they willform a solid (i.e. not hollow) spherical ball. Many embryos

start out with, or pass through, such a configuration, anduniform balls of cells are found in fossil beds of the Edia-caran periodat thedawn of animal evolution. If cells within

an aggregate have different degrees of adhesiveness, asoccurs in a regulated fashion in later stages of animal

embryogenesis, but would have also arisen in primitive

metazoan ancestors in the course of evolution due to laxregulation of gene expression, a novel configuration auto-matically emerges. As seen in experiments in which cells

which only differ in surface adhesion are randomly mixed,the different populations will sort out, forming a multi-

layered structure with interfaces between the layers, acrosswhichcells will not intermix (Steinberg, 2003). This sorting-out behaviour may be driven entirely by differential adhe-sion, but it is also promoted by differences between the celltypes in the tension the cytoskeleton exerts on the corticalcytoplasm just beneath the cell surface (Krieget al., 2008).Subdivisions of tissues based on differential affinity, if (as isoften the case) they also represent distinct cell lineages, aretermed compartments.See also:Adhesive Specificity andthe Evolution of Multicellularity

This phenomenon is similar to what occurs when twoimmiscible liquids, such as oil and water, are shakentogether and allowed to separate. In cellular systems,in place of the chemical free energy whose minimizationgoverns the phase separation of liquids, an energy functionat the cellcell interface that combines adhesive strengthand cellcortex tension is minimized (Krieg et al., 2008).Gastrulation, the set of developmental processes by whichtissue layers and their relative positions are achieved duringembryogenesis, is a hallmark of most metazoan groups.Although the precise spatiotemporal organization of suchbehaviours has come under the control of gene expressionprogrammes in present-day organisms, they likely origin-ated in the minimization of interfacial energy that drivesthe sorting-out behaviour of different cell populations.

See also: Cleavage and Gastrulation in Leech Embryos;Cleavage and Gastrulation in Mouse Embryos;Cleavageand Gastrulation in the Sea Urchin; Cleavage andGastrulation in Zebrafish Embryos

Diffusion, concentration gradients andlateral inhibition

Diffusion is a physical process that produces eithermolecular uniformity or nonuniformity depending onthe time and spatial scale over which it acts. Over thedimensions of an individual cell diffusion would quickly

erase any heterogeneity. But since the intracellular envir-onment is crowded and complex, free diffusion plays only alimited role in the cell interior. On the scale of a cellaggregate, in contrast, diffusion promotes the formation ofgradients of released molecules (Crick, 1970). In ancientcellular clusters, a group of cells that released a product at ahigher rate than their neighbours either by a spon-taneous, stochastic effect or because something in theirenvironment induced them to do so would have taken on

a privileged, organizing role in the aggregate. It is notnecessary that the organizer cells be predetermined: oncethey arise they have global patterning consequences,

imparting a spatially nonuniform microenvironment to theclusters cells.

Morphological Evolution: Epigenetic Mechanisms

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Thepatterning role of a diffusiblemoleculeis enhancedif

it signals surrounding cells not to acquire the same state orproduce the same molecule, an effect known as lateralinhibition. Since the unicellular organisms that preceded

the Metazoa had biochemical circuitry enabling them toswitch between alternative states (see later discussion), it

would have not taken much additional genetic evolution toform regulatory networks known as reactiondiffusion, orlocal autoactivationlateral inhibition (LALI), systems(Meinhardt and Gierer, 2000). Such systems can generatespatial periodicities such as in the digits of the limbs anddentition of vertebrates, hair follicles in mammals andbristles in insects, and pigment patterns in fish and snails(Turing, 1952; Meinhardt, 2008; Newman et al., 2008).Present-day embryos continue to employ diffusible signalmolecules (called morphogens) to generate regional dif-ferences during development, but the propagation of theireffects have often become, over the course of evolution,integrated with other cell functions.See also:Modelling ofPlant Growth and Development; Vertebrate Embryo:Establishment of Left-Right Asymmetry

Cell polarity, lumen formation andelongation

The first multicellular organisms were likely to have beencomposed of cells with a uniform, or random, distributionof adhesive molecules on their surfaces. Many modern celltypes, in contrast, are polarized, capable of allocating dif-

ferent molecular species to their apical and basolateral

regions. The targeting of adhesive molecules, or anti-adhesive molecules, to specific regions of the cell surface

has dramatic consequences. A tissue mass consisting ofmotile cells that are nonadhesive over portions of theirsurfaces will readily develop cavities or lumens (Tsarfatyet al., 1994). If such spaces come to adjoin one another as aresult of random cell movement, they will readily fuse.Lumen formation could therefore have originated as asimple consequence of differential adhesion in cells thatexpress adhesive properties in a polarized fashion. See also:Adhesive Specificity and the Evolution of Multicellularity;Multicellular Organs and Organisms

Significantly, the first morphologically complex multi-

cellular organisms, represented by the Ediacaran fossildeposits dating from more than 600 million years ago, weresolid-bodied creatures. Among modern groups, the coel-enterates such as comb jellies and hydra are forms witha single lumen, whereas echinoderms (e.g. starfish) andvertebrates have both a digestive tube and a surroundingbody cavity. By around 580 Ma animals with distinct bodycavities appeared in the fossil record. Over the following 50million years all the major animal phyla had arisen. It has

been speculated that the advent of polarized cells, and thestraightforward physical consequences of this step, mayhave provided the basis for the rapid profusion of body

types during the late Precambrian and Cambrian periods.See also:Cambrian Radiation;Diversity of Life

Another type of cell polarity pertains to cell shape. The

spherical clusters that comprise the early embryonic stagesof many present-day species and the embryo-like fossils ofthe Ediacaran deposits (Yinet al., 2007) contain cells that

are themselves round or amorphous. But some cells canundergo planar polarization, which causes them to

lengthen in the plane perpendicular to their apico-basalaxis. These planar-polarized cells will tend to maximizetheir adhesive contacts along their long axes. The resultingintercalation will lead to a simultaneous shortening of themulticellular aggregate in the direction of the cells longaxes and (because of mass conservation) a lengthening inthe orthogonal direction, a process termed convergentextension (Keller et al., 2000). The elongated body axes,characteristic of most animals, likely have their evo-lutionary origin in the collective behaviour of cells capableof undergoing planar polarization.

Oscillations, morphogenetic fields andsegmentation

The existence in all cells of positive and negative bio-chemical feedback loops will often lead to temporal oscil-lations in one or more molecular component (Goldbeter,1996). The cell cycle is in fact based on such oscillations.Others of these periodic activities may have no explicitfunctional roles, arising as spontaneous side effects of thegene regulatory circuitryrather than as theexpressionof anevolved network.

Once cells that were capable of exhibiting such oscil-

lations became incorporated into aggregates or primitivetissues, the effect of scale was again played out in terms of

novel, physically determined effects. Weakly interactingoscillators of all kinds tend spontaneously to come intosynchrony, and living cells, ranging from bacteria withartificially engineered biochemical oscillators to heart cellsin tissue culture, are no exception. Since no special mech-anisms areneeded to bring about synchronization, it wouldhave occurred in any primordial cluster of cells that con-tained oscillatory circuits. This phenomenon is employedin the paraxial mesoderm of vertebrate embryos, where itcoordinates cell states and behaviours over broad regionsof tissue (Giudicelliet al., 2007).

Synchronization of oscillating cell states is probably thebasis of many of the phenomena described as morpho-genetic fields by classical embryologists (Newman andBhat, 2009). In certain cases like the vertebrate embryo theoscillation underlying the paraxial mesodermal field ismanifested when tissue cohesivity becomes linked to aparticular phase of the molecular clock (Deque ant andPourquie , 2008). Segmentation (called somitogenesis invertebrates) has apparently been independently evolved

more than once in the history of the animals (i.e. arthro-pods, annelids, vertebrates or arthropods+annelids andvertebrates), andis likelyin some cases to be a byproduct of

developmental dynamics rather than a functional adap-tation. See also: Somitogenesis in Vertebrate Development


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Developmental-genetic toolkit, dynamicalpatterning modules and animal development

The physical processes described earlier that mediatemorphogenesis and pattern formation can only act on cellaggregates and tissues if molecular components capable of

harnessing them are present. In the case of the metazoans,molecules of this kind were already in place before theappearance of multicellularity, in theformof a subsetof theproducts of the developmental-genetic toolkit. Thetoolkit genes, which specify proteins that regulate tran-scription as well as ones that regulate cell attachment,communication and surface and shape polarity, are well-known to perform corresponding roles across all the ani-mal phyla (Wilkins, 2002). Many of these genes are presentin theChoanozoa, a sistercladeof theMetazoa (Shalchian-Tabrizi etal., 2008). Choanozoans are generally unicellularor transiently colonial (Lang et al., 2002). Their geneticsimilarity with animals indicates that their commonancestor with the animals, a Precambrian unicellularorganism, already had the capacity to mobilize forces thatcould mediate the formation of multicellular clusters andthen shape and organize them. See also: ProtozoanEvolution and Phylogeny

The best-characterized choanozoan, the choano-flagellateMonosiga brevicollis, contains several genes spe-cifying cadherins, the family of proteins that mediate cellcell adhesion in theembryonic tissues of allanimal embryos(Abedin and King, 2008). Since cadherins only perform

this function in the presence of sufficient concentrations ofcalcium ion, ambient conditions can have caused single-

celled organisms bearing these molecules to becomemulticellular aggregates. Choanozoan genomes also spe-cify lectins (glycan-binding proteins), domains of theextracellular matrix (ECM) protein collagen and integrin-typeECM receptors, functional portions of the morphogenHedgehog, as well as cell surface and intracellular com-ponents of the Notch pathway, which mediates lateralinhibition in metazoan embryos (Ehebauer et al., 2006;King et al., 2008; Shalchian-Tabrizi et al., 2008). Sincelateral inhibition is an intrinsically multicellular function,the Notch pathway may have evolved in single-celledorganisms to perform the related role of influencing thechoice between alternative cell states. See also: Cell Surface

Glycoconjugates; Drosophila Patterning: DeltaNotchInteractions; Extracellular Matrix; Hedgehog Signalling;Integrin Superfamily;Lectins

The Wnt pathway, including families of secreted ligandsand receptors, has two branches, one that mediates apico-basalcell polarity and theother planar cell polarity (Angersand Moon, 2009). Although no Wnt components have yetbeen identified in a choanozoan, two divergent basal

metazoans with simple but distinct body plans, the spon-ges, with a characteristic labyrinthine morphology, and aplacozoan, a solid-bodied three-layered organism, contain

Wntpathwaygenes. Thespongeshave both branches of thepathway (Adell et al., 2007) and the placozoan only theapico-basal polarity branch (Srivastava etal., 2008). These

findings suggest that a single-celled common ancestor ofthese organisms either contained elements of both Wntpathways or that the planar cell polarity branch was lost inthe Placozoa lineage. See also:Mammalian Embryo: Wnt

Signalling;Placozoa;Porifera (Sponges)The presumed single-celled ancestors of the Metazoa

therefore contained genes that took roles in the multi-cellular context different from the ones they had evolved to

perform, due to their products entering into associations(termed dynamical patterning modules; Newman andBhat, 2009) with particular physical processes, forces oreffects. The results cellcell adhesion, lumen and com-partment formation, generation of morphogen gradients,convergent extension, segmentation, appendage formationand skeletogenesis facilitated rapid morphological evo-lution during the early history of the animals. The mor-phological motifs that arose from the action of dynamicalpatterning modules have been constant themes in thegeneration of body plans and organ forms over the suc-ceeding half billion years.

Interplay of Generic and Program-matic Mechanisms of Development

The combined effects of the various physical properties thatwere generic to the earliest multicellular aggregates madevirtually inevitable a profusion of layered, hollow, elong-ated, segmented, appendage-bearing forms early in the his-

tory of metazoan life. Although the somatic organization of

these ancient organisms resembled in many respects that oftheir modern counterparts, their developmental modes and

mechanisms were very different. In particular, the con-ditional and interactive nature of the physical forces thatmoulded these early organisms are likely to have renderedthem morphologically plastic (West-Eberhard, 2003), withgiven genomes often being consistent with reversibly inter-convertible forms. Only with the subsequent evolution ofgenetic redundancy and biochemical integration, leading togenetic co-optation of forms that originated with strongphysical dependence by hardwired regulatory circuitry,would organisms of the more familiar modern variety haveemerged: entities in which bodily form is achieved with

decreased participation of external physical forces andincreased dependence on programmatic genetic control(Newmanet al., 2006;Figure 1).

Although natural selection, particularly of the stabil-izing andcanalizing variety, plays an importantrole in suchgenetic assimilation, the basic morphological motifs andphenotypes which are subject to selection were largelymanifestations of the inherent properties of cell aggregatesand tissue masses rather than incrementally achieved

adaptations. The recognition that the origination of mor-phological motifs may be different from the means of theirrealization in present-day organisms represents a contri-

bution of evolutionary developmental biology (EvoDevo)that departs from classical evolutionary narratives.


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See also:Evolutionary Developmental Biology: Develop-

mental and Genetic Mechanisms of Evolutionary Change;Evolutionary Developmental Biology: Gene Duplication,Divergence and Co-option;Genetic Redundancy

Epigenetics of Advanced Development

Once basic body plans were established, selection for bio-

chemical integration, promoting physiological homeo-stasis and developmental reliability stabilized therelationship between genotype and phenotype. The dom-

inant role of genetic control in these more advanceddevelopmental systems is undisputed, and its proximateworkings in modern species represent the primary researchfocus of modern developmental biology. But even in highlycontrolled forms of development the realization ofmorphology, particularly at the level of organogenesis,

continues to depend on nonprogrammatic, epigeneticmechanisms. Among these are physicochemical, topolo-gical and biomechanical factors, as well as generic, sto-chastic and self-organizational properties of developingtissues, and the complex dynamics of interactions betweenthese tissues (Salazar-Ciudadet al., 2003). Although thereis ample empirical evidence for the participation of thesefactors in individual ontogenies, their influence in settingtrajectories of morphological evolution is only recentlycoming to be incorporated into the framework of evo-lutionary theory (Mu ller, 2007; Salazar-Ciudad, 2006).See also:Morphology and Disparity through Time

Nonprogrammed processes of development

Genetically controlled development acts through a host ofbiomolecules by which cells regulate one anothers activities(Davidson, 2006). At the initial stages of development therelationship between gene expression in a given cell and theresulting behaviour of that cell and its neighbours can bedirect and rather immediate. Subsequent phases of devel-opment, however, involve increasing numbers of differen-tiated cell populations that produce molecularenvironmentsof ever greater variety and complexity. The composition ofthese local microenvironments influences cells in a broad-

ening, combinatorial fashion and the behaviour of indi-vidual cells becomes highly context dependent. Withintensifying complexity of interactions, the developmentalprocesses become increasingly removed from direct andexclusive control by the genome. And unless specific mech-anisms exist to oppose their actions, the material propertiesof tissue primordia willcontinueto be of decisive importancein the organization of embryonic structures.

Many of these contextual and generic determinants of

development are the same as or related to the dynamicalpatterning modules described above. Others are due tomore complex tissue properties (Larsen, 1992). Instruc-

tions for general processes and even for very specific eventsin development can arise from the internal environment,

Figure 1 Schematic representation of evolutionary partitioning of a

morphologically plastic ancestral organism into distinct morphotypes

associated with unique genotypes. (a) A hypothetical primitive metazoan isshown with a schematic representation of its genome in the box below it.

Developmental-genetic toolkit genes, specifying both transcription factors

and molecules involved in form-and-pattern-determining dynamical

patterning modules are shown as coloured geometric objects; interactions

between them by lines. Determinants of the organisms form include the

products of expression of its genes (blue arrows extending from genomes

to forms) and the physico-chemical external environment (broad purple

arrows pointing to forms) acting on its inherent physical properties.

At this stage of evolution the organism is highly plastic, exhibiting

several condition-dependent forms that are mutually interconvertible

(dark horizontal arrows). (b) Descendants of organism in (a) after some

stabilizing evolution. Gene duplication, mutation, etc. have led to

genetic integration and assimilation of some outcomes that were

previously more dependent on the environment, as well as some

subpopulations being biased towards subsets of the original morpho-

logical phenotypes. Determinants of form are still gene products, inherent

physical properties and the physical environment, but the effect of the

latter has become attenuated (smaller, fainter purple arrows from the top)

as development has become more programmatic. There is also an influence

of the form on the genotype (orange arrows from forms to genomes),

exerted over evolutionary time, as a well-established morphological

phenotype acts as a selective filter against those variant genotypes that are

not compatible with it. Some morphotypes remain interconvertible at this

stage of evolution, but others are not. (c) Modern organisms descended

from those in (b). Further stabilizing evolution has now led to each

morphotype being uniquely associated with its own genotype. Physical

causation is even more attenuated (faint purple arrows), but influence of

the form itself over acceptable genetic and gene interaction changes is

increased. Note that in this idealized example the forms have remained

unchanged whereas the genes and mechanisms for generating the forms

have undergone extensive evolution. Adapted, with changes, fromNewman et al. (2006).


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for example, maternal factors present in the egg (Badyaev

and Uller, 2009), or the external environment (includingthe uterine environment in mammals), which can stronglyinfluencedevelopment via its chemical composition, energy

supply, temperature, humidity, gravity, mechanical stress,spatial confinement, illumination intensity and periodicity,

etc. (Gilbert and Epel, 2009).Many events of early development, such as the initiation

of the body axis or of neural tube formation, or of latedevelopment, such as muscle individuation, innervationpatterns or blood vessel growth, depend on inductiveinteractions between tissues. The sites of these interactionsare not necessarily predetermined, but may simply requirethe meeting of a sender and a receiver tissue. Where thisactually occurs can depend on stochastic factors, such ascell number, sizes of the primordia, distance betweencompetent tissues, etc. The activity of the embryo itself canalso contribute to the appropriate development of the size,shape and arrangement of body components (Mu

ller,

2003a). In consequence, the deployment of genetic infor-mation itself during all stages of development is underepigenetic control (see also Jablonka and Lamb, 2005).

Rapid change and the origin ofmorphological novelty

Because of thepervasive role of epigenetic processesin bothancient and modern developmental systems, accounts ofmorphological evolution cannot be reduced to the evo-lution of molecules and genes. Epigenetic determinants of

tissue morphogenesis are responsible for many heretofore

puzzling phenomena in morphological evolution, such asinstances of rapid morphological change and the emer-

gence of new structural features at the subphylum level.See also:Evolutionary Ideas: Darwin;Evolutionary Ideas:The Modern Synthesis

Since gene change by mutation is relatively constant, thegeneral expectation of thestandardtheory was that therateof morphological change within a phylogenetic lineageshould also remain fairly constant. But, in strong contrastto this prediction, the fossil record documents numerouspunctuated events (Eldredge and Gould, 1997; Jablonski,2005). Molecular phylogenies, moreover, provide no indi-cation that episodes of rapid morphological change in

recent species diversifications must be accompanied byaccelerated genetic change. Analysis of inbred mousestrains and of developmental perturbation experimentslead to similar conclusions: rapid, extensive changes ofmorphology are not necessarily linked to correspondingamounts of genetic change. The epigenetic character ofdevelopmental systems supplies the critical explanatorymode missing from exclusively gene-centred accounts ofthe tempo and mode of evolution (Newman, 2006; Mu ller,

2007). See also:Molecular Phylogeny ReconstructionThe epigenetic dimension of developmental systems can

also provide insight into another characteristic of mor-

phological evolution that has up till now eluded explan-ation, namely the appearance of new characters in a

phylogenetic lineage. The generic, self-organizing and

conditional, interactive character of the epigenetic deter-minants discussed earlier provide a natural account forsuch innovations (Newman and Mu ller, 2000; Mu ller and

Newman, 2005). Genetic change, intraembryonic tissueinteractions and interaction of the organism with the

external environment can all lead to the crossing ofthresholds in the equilibria of developmental interactions,and the reactive properties of the affected tissues createkernels of new morphological structures. Explanations ofnovelty that invoke genetic change alone fail to address theactual basis of phenotypic change. See also:Macroevolu-tion: Overview;Origin of Novelties

For example, the relation between alteration in tensileinteractions among embryonic tissues and the appearanceof novel skeletal structures in the vertebrate embryo(Mu ller and Streicher, 1989; Mu ller, 2003a) provide amechanism by which gradual evolutionary changes in theproportions of pre-existing elements can abruptly generatesuch novelties when developmental thresholds are crossed.These system-specific byproducts of the evolutionarymodification of developmental processes take the form ofphenotypic innovations. Once in place, they are susceptibleto becoming reinforced and stabilized in their realizationby additional genetic change under standard Darwinianselection regimes. The process described represents a firststep towards the establishment of new homologues inphylogenetic lineages.

Origin of Morphological Homology

The evolution of morphological phenotypes is a continuing

process of generation and organization of anatomicalstructures. Recurrent units of morphological organizationwith common ancestry have traditionally been calledhomologues, and have been used for systematic and tax-onomical purposes for centuries. Their establishment andthe basis of their stability, however, have eluded explan-ation within the classical evolutionary framework. But newconcepts provided by EvoDevo, including the relationship,described earlier, between genetic and epigenetic factors ofmorphogenesis, enable a causal-mechanistic account ofmorphological evolution and homology. Homology has

thus become a core component of an expanded evo-lutionary framework (Pigliucci and Mu ller, 2010). Seealso:Homology in Character Evolution

Three steps have been described in the establishment ofmorphological homology, namely the generation, the fix-ation and the autonomization of individualized con-structional elements (Mu ller and Newman, 1999). Asdiscussed earlier, the first step, the generation of newbuilding elements, will often be a consequence of dynam-

ical patterning modules and other epigenetic propertiesof developmental systems under changed conditions(Figure 2a). Next, the fixation of new elements within

existing body plans will occur with the progressive inte-gration of phenotypic, developmental and genetic levels of


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interaction, typically as a result of standard scenarios ofnatural selection. Phenotypic novelties initially broughtabout by epigenetic mechanisms will increasingly come torely on genetic control for their ontogenetic realization.Since selection favours the genetic linkage of functionallycoupled characters (Bu

rger, 1986), functional inter-

dependencies that become established at the phenotypic

level will contribute to a further locking in of new char-

acters and will gain increasing organizational importanceas increasingly elaborate design features are incorporated.The result is an ever closer mapping between genotype and

phenotype (Figure 2b).But the evolution of homology does not stop at this

point. Once new building elements have become integratedinto thebody designof a taxon,they cangain independencefrom the mechanisms responsible for their initial estab-lishment. This is suggested by those cases in which differentontogenetic pathways are employed for the realization ofthe same structures in different species. Skeletogenesis insea urchins, for example, involves the use of different pro-genitor lineages in direct developing species than it does inthose that pass through a larval stage (Wray and Raff,1989). The orbitosphenoid, a component of the skull,develops as membrane bone in worm lizards but asreplacement bone in other vertebrates (Bellairs and Gans,1983). Meckels cartilage of the mandibular arch is inducedby the endoderm in amphibians but by the ectoderm inhigher vertebrates (Hall, 1983). Segmental developmentin long germ band insects such as the fruitfly differsconsiderably from this process in short germ band insectslike beetles, whereas the resulting structures are clearlyhomologous. In other cases the expressed genes and even-tual molecular make-up of embryonic structures havechanged during evolution of a lineage (Kiontke et al.,

2007). See also: Evolutionary Developmental Biology:Homologous Regulatory Genes and Processes

These examples demonstrate that the same phenotypicend-point can be reached by alternative developmental

modes and pathways. In other words, morphologicalhomology persists while its molecular, genetic and devel-opmental components become free to drift (True andHaag, 2001), a process that has been termed autono-mization (Mu ller and Newman, 1999;Figure 2c). But sincethe homologues themselves are maintained as con-structional units of the phenotype, they assume a role asindependent organizers of body design and of the evolvinggene regulatory hierarchy (the Organizational HomologyConcept; Mu ller, 2003b). In this account, phenotypicorganization and the evolution of morphological formbecomes strongly determined by the specific set of homo-logues that a phylogenetic lineage has acquired.

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Mu ller GB and Newman SA (eds) (2003) Origination of Orga-

nismal Form: Beyond the Gene in Developmental and Evo-

lutionary Biology. Cambridge, MA: MIT Press.

Raff R (1996) The Shape of Life: Genes, Development, and the

Evolution of Animal Form. Chicago: The University of Chicago

Press.

Sole R and Goodwin B (2000) Signs of Life. New York: Basic

Books.



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