EVOLUCIÓN

DEPARTAMENTO DE ECOLOGÍA, GENÉTICA Y EVOLUCIÓN

FACULTAD DE CIENCIAS EXACTAS Y NATURALES

UNIVERSIDAD DE BUENOS AIRES

2° CUATRIMESTRE 2020

GUÍA DE TRABAJOS PRÁCTICOS

MÓDULO 7

EVOLUCIÓN Y DESARROLLO

1

EVOLUCIÓN Y DESARROLLO

(EVO-DEVO)

“Evolution occurs when ontogeny is altered in one of two ways: when new characters are

introduced at any stage of development with varying effects upon subsequent stages, or when

characters already present undergo changes in developmental timing”.

S. J. Gould en “Ontogeny and Phylogeny” (1977)

BREVE INTRODUCCIÓN

El término “evolución” fue usado por los preformacionistas del siglo XVIII para describir el

proceso por el cual un embrión crece hasta convertirse en un organismo adulto. Esta es la primera

connotación biológica del término y difiere claramente de su significado actual. Los

preformacionistas creían que el embrión estaba ya ubicado dentro de la célula germinal con todas

sus partes ya formadas y simplemente crecía en tamaño hasta alcanzar el estado adulto. El ejemplo

extremo de este punto de vista es el del homúnculo, el hombrecito con proporciones de adulto

dibujado dentro del esperma. Malpighi y Bonnet (ambos representantes del Preformacionismo)

habían estudiado el desarrollo del embrión de pollo y conocían el aumento de complejidad aparente

al microscopio (poco coherente con las ideas preformacionistas). A pesar de ello afirmaban que lo

que veían era ilusorio y estaba sesgado por los instrumentos usados y los sentidos.

En el siglo XIX, con el nacimiento de la Embriología comparada, comienzan a oírse otras voces

que hablan del desarrollo. Ètienne Geoffroy SaintHilaire sugiere que la homología de una estructura

puede ser inferida por las relaciones con otras estructuras durante el desarrollo embrionario. A

diferencia de Cuvier, que dividía los animales en cinco clases sin relación entre sí, Geoffroy sostenía

que todos los animales compartían grandes similitudes en su anatomía.

En el mismo siglo, Haeckel expone su visión recapitulacionista. Considera que la filogenia es

la que determina la ontogenia, ya que los animales pasan durante su desarrollo por las formas

adultas de otras especies “inferiores”. El cigoto humano representa al protista adulto, la blástula

humana representa a los protistas coloniales, el estadio humano de arcos branquiales al pez adulto,

etc. Las nuevas especies evolucionan adicionando un paso más en el desarrollo. Igualmente, Haeckel

manifiesta que es factible un acortamiento del desarrollo en algún tramo para evitar un infinito

tiempo de gestación. En 1828, Karl Ernst Von Baer enuncia algunos puntos importantes en sus

leyes del desarrollo:

1. Las características generales de un gran grupo de animales aparecen antes en el embrión

que las características particulares de un grupo menor.

2. Los animales no pasan durante su desarrollo a través de formas adultas de otros

organismos “inferiores” (contradice a los recapitulacionistas).

3. Los embriones de especies emparentadas comparten estadios tempranos de desarrollo

pero divergen en los estadios más tardíos.

4. Los caracteres más especializados se desarrollan a partir de estructuras generales

compartidas por distintas especies.

2

El trabajo de Von Baer influyó fuertemente en el pensamiento de Darwin, quien consideró

las similitudes en el desarrollo de distintas especies como evidencia de ancestralidad común. Fritz

Müller (un acérrimo defensor del Darwinismo) y Francis Balfour resaltan en sus escritos la

importancia de la Embriología Comparada como herramienta para dilucidar las relaciones

filogenéticas. Afirman también, que la selección natural debe actuar tanto en los estadios larvales

como en los adultos.

En el siglo XX, el advenimiento de la “Teoría Sintética de la Evolución” acerca la Genética a

la Evolución en detrimento de la Biología del Desarrollo. Esta última es uno de los capítulos faltantes

en la “Síntesis”. Las causas de esta importante ausencia pueden haber sido muchas, pero la más

importante parecería ser la falta de entendimiento entre genetistas de poblaciones y embriólogos.

En los ‘40s Richard Goldschmidt, sostiene que la evolución puede ocurrir sólo por cambios

heredables en los genes que regulan el desarrollo. Para él los genes son más que loci y alelos, son

unidades de desarrollo. Las nuevas especies se originan como “monstruos esperanzados” (“hopeful

monsters”) que resultan de mutaciones sistémicas que afectan el desarrollo del animal. Su visión, al

ser contraria a la neodarwinista, no es tenida en cuenta en su época. En 1977, Stephen Jay Gould,

publica el libro Ontogeny and Phylogeny y reaviva en el ambiente científico el interés por la Biología

del Desarrollo como herramienta para estudiar la evolución.

En 1978, E.B. Lewis descubre los genes Hox (los encargados de dar identidad a cada parte

del animal a lo largo del eje anteroposterior) y unos años más tarde comienza a conocerse en

profundidad el desarrollo embriológico de Drosophila melanogaster, Caenorhabditis elegans y del

ratón. Paralelamente, la Biología Molecular avanza a pasos agigantados y provee nuevas

herramientas de análisis. Estos hechos recientes marcan el comienzo de la EvoDevo moderna.

En la actualidad la interfase entre Evolución y Desarrollo atraviesa un renacimiento. En él

convergen disciplinas como la Biología del Desarrollo, la Ecología, la Embriología, la Paleontología,

la Genómica y el Análisis Filogenético. Esta combinación de enfoques y metodologías tiene como

objetivo desentrañar los mecanismos y patrones del desarrollo que originan la diversidad de formas

vivientes que existen en nuestro planeta.

BIBLIOGRAFÍA CONSULTADA

Carroll S.B., Grenier J.K. and Weatherbee S.D. 2005. From DNA to diversity, Second Edition. Blackwell

Publishing.

Gilbert S.F. 2003. Developmental Biology, 7th Edition. Sinauer Associates.

Gilbert S.F. 2003. The morphogenesis of evolutionary developmental biology. Int.J.Dev.Biol. 47(78):

46777.

Gould S.J. 1977. Ontogeny and Phylogeny. Belknap Press of Harvard University Press.

Hall B.K. 2003. EvoDevo: evolutionary developmental mechanisms. Int.J.Dev.Biol. 47(78): 4915.

Wilkins A.S.2002. The evolution of developmental pathways. Sinauer Associates.

3

TRABAJO PRÁCTICO N°1: SEMINARIO

Lea atentamente los siguientes trabajos y responda las preguntas:

1. Angelini, D. R. & Kaufman, T. C. (2005). Comparative developmental genetics and the

evolution of arthropod body plans. Annu. Rev. Genet. 39: 95-119. (Fragmento).

1. ¿Cuál es la propiedad de la biodiversidad que aborda este trabajo como problemática general?

¿Cómo la definen estos autores? ¿Se aplica este concepto a una escala taxonómica específica?

2. ¿En qué grupo de organismos se enfoca el trabajo? ¿Qué son los genes Hox, cuál es su función y

cómo operan? ¿Qué particularidades presentan?

3. ¿Qué es la tagmosis y cuál es su importancia sistemática? ¿En qué consiste su evolución desde el

punto de vista morfológico-funcional?

4. ¿Cómo se relacionan los genes Hox con los patrones de tagmosis de los artrópodos?

5. A partir de la Figura 1 del trabajo de Angelini y Kaufman, especule cómo podría haberse originado

evolutivamente el patrón de tagmosis de los insectos a partir de cambios en los patrones de

expresión de los genes Hox en un ancestro con una tagmosis y expresión similar a la de los

miriápodos.

2. Galis, F. (1999). Why do almost all mammals have seven cervical vertebrae?

Developmental constraints, Hox genes and cancer. J.Exp.Zool. 285: 19-26.

1. ¿Cuál es la restricción (constraint) al cambio sobre la que versa el trabajo? ¿Existe variación

intraespecífica del número de vértebras en las distintas regiones de la columna de los mamíferos?

2. ¿Qué distingue una vértebra torácica de una cervical? ¿Qué es una costilla cervical? ¿Cuáles son

las patologías asociadas con las costillas cervicales?

3. ¿Qué otra función de los genes Hox se menciona en este trabajo en relación con el trabajo

anterior? ¿Qué patologías tienen los ratones mutantes de algunos genes Hox o Polycomb?

4. La restricción al cambio en el número de vértebras cervicales: ¿está dada por ausencia de

variación para ese carácter o por selección en contra de variantes de ese carácter? ¿Cómo se

presenta en humanos la selección estabilizadora?

5. ¿Cuál es la conclusión de la autora respecto de la relación entre el número conservado de

vértebras cervicales, el cáncer y los genes Hox en mamíferos? ¿Por qué esta relación no se

presentaría en reptiles y anfibios?

4

ANRV260-GE39-06 ARI 15 October 2005 11:51

ComparativeDevelopmental Geneticsand the Evolution ofArthropod Body PlansDavid R. Angelini1 and Thomas C. Kaufman2

1Department of Ecology and Evolutionary Biology, University of Connecticut, Storrs,Connecticut 06269-3043; email: david.angeliniguconn.edu2Department of Biology, Indiana University, Bloomington, Indiana 47405-3700;email: kaufman@bio.indiana.edu

Annu. Rev. Genet.2005. 39:95–119

First published online as aReview in Advance onJune 21, 2005

The Annual Review ofGenetics is online athttp://genet.annualreviews.org

doi: 10.1146/annurev.genet.39.073003.112310

Copyright c© 2005 byAnnual Reviews. All rightsreserved

0066-4197/05/1215-0095$20.00

Key Words

comparative developmental genetics, Arthropoda, body plan,Hox genes, insect wing modifications

AbstractThe arthropods display a wide range of morphological diversity,varying tagmosis, as well as other aspects of the body plan, such asappendage and cuticular morphology. Here we review the roles ofdevelopmental regulatory genes in the evolution of arthropod mor-phology, with an emphasis on what is known from morphologicallydiverse species. Examination of tagmatic evolution reveals that thesechanges have been accompanied by changes in the expression pat-terns of Hox genes. In contrast, review of the modifications to wingmorphology seen in insects shows that these body plan changes havegenerally favored alterations in downstream target genes. These andother examples are used to discuss the evolutionary implications ofcomparative developmental genetic data.

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Contents

INTRODUCTION. . . . . . . . . . . . . . . . . 96Comparative Developmental

Genetics and the Hox Genes . . 97What is the Meaning of the

“Body Plan” Concept? . . . . . . . . . 97What Defines the Arthropod Body

Plan? . . . . . . . . . . . . . . . . . . . . . . . . . 98DEVELOPMENTAL GENETICS

OF ARTHROPOD TAGMOSIS . 98Evolution of the Arthropod Head . 98Hox Genes and Tagmosis . . . . . . . . . 99The Recruitment of Maxillipeds in

Crustacea . . . . . . . . . . . . . . . . . . . . . 101Reduction of Tagmata in Some

Lineages . . . . . . . . . . . . . . . . . . . . . . 102EVOLUTION OF LESSER BODY

PLAN FEATURES IN INSECTS 103The Origin of Wings . . . . . . . . . . . . . 104Suppression of Prothoracic and

Abdominal Wings in ModernInsects . . . . . . . . . . . . . . . . . . . . . . . . 105

Differentiation of Forewings andHindwings . . . . . . . . . . . . . . . . . . . 105

The Evolution of DipteranHalteres from Hindwings . . . . . . 106

The Evolution of Elytra fromForewings in Coleoptera . . . . . . . 106

Phylogenetic Homeosis Among theStrepsiptera? . . . . . . . . . . . . . . . . . . 107

The Appearance of WinglessnessAmong Insects . . . . . . . . . . . . . . . . 107

The Evolution of Foreleg Combs . 109DISCUSSION . . . . . . . . . . . . . . . . . . . . . 110

Implications of DevelopmentalSystems Drift . . . . . . . . . . . . . . . . . 110

Integrating ComparativeDevelopmental Conclusionsinto Evolutionary Biology. . . . . . 111

Evidence for Hopeful Monsters . . . 112Genetic Evidence for Infinitesimal

Morphological Evolution . . . . . . 112Future Directions . . . . . . . . . . . . . . . . 113

INTRODUCTION

The diversity of animal life is one of ourworld’s most mysterious and intriguing qual-ities. Individual species have multiplied to fillecological niches through a dizzying arrayof physiological and morphological modifica-tions. Modern evolutionary biology has be-gun to understand the mechanisms involvedin speciation (28, 98). However, one of theprincipal and persistent mysteries remains theorigins and evolution of the novel morpholo-gies and body plans that arise among diversespecies (71). In recent decades, investigatorsof comparative developmental genetics haveapplied tools and ideas from molecular anddevelopmental biology to some of the ques-tions of morphological evolution with heart-ening success. This new field has also beenknown as phylontogenetics, or more com-monly “evo-devo”—the truncated catchall

named for two of its most influential parentdisciplines, evolutionary and developmentalbiology.

One of the animal groups that has beena major beneficiary of comparative devel-opmental genetics is the Arthropoda. [Theothers are vertebrates, basal chordates, anddeuterostomes (e.g., 43, 66, 79).] Since theirappearance in the Cambrian, approximately530 mya, arthropods have dominated the an-imal world. They have evolved myriad vari-ations on an anatomical theme. In practi-cal, experimental terms, arthropod evo-devohas flourished as it has drawn on the well-established fields of entomology, carcinology(the study of crustaceans), and genetics. Thefirst two have described a wealth of diversemorphology and body plans, while the latterhas provided tools and new developmental hy-potheses for their investigation.

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Comparative DevelopmentalGenetics and the Hox Genes

The homeotic complex (Hox) genes haveemerged from genetic studies of the fruitfly,Drosophila melanogaster, as crucial early reg-ulators of segment identity, and thus bodyplan organization, in arthropods. Hox genesare homeodomain transcription factors, re-markably well conserved in sequence and ex-pression across the arthropods and other ani-mals. Therefore, they provide a reliable andaccessible experimental inroad to the studyof diverse body plans. In general, Hox genesare expressed alone or in overlapping do-mains of adjacent body segments. They ex-hibit the intiguing feature of “colinearity,”appearing in the gene complex in the or-der in which they are expressed along theanterior-posterior (AP) body axis. Ten Hoxgenes are expressed along the body of mostarthropods, where they are usually named fortheir orthologues in Drosophila. From ante-rior to posterior, these are labial (lab), probosci-pedia (pb), Hox3/zen, Deformed (Dfd ), Sex combsreduced (Scr), Hox6/ftz, Antennapedia (Antp),Ultrabithorax (Ubx), abdominal-A (abd-A), andAbdominal-B (Abd-B). In the insects, Hox3/zenand Hox6/ftz have been modified and do notfunction as typical Hox genes in this group(48).

Hox genes specify the identity of bodysegments and structures where they are ex-pressed, and mutations result in a homeotictransformation to some other fate, often to amore posterior identity (reviewed in 47). In1978, characterization of the homeotic bitho-rax mutations of Drosophila led Ed Lewis topresage the growth of comparative Hox workthat would come decades later:

Flies almost certainly evolved from insectswith four wings instead of two and insectsare believed to have come from arthropodforms with many legs instead of six. Duringthe evolution of the fly, two major groups ofgenes must have evolved: “leg-suppressing”genes which removed legs from abdomi-

AP:anterior-posterior, asin anterior-posteriorbody axis

Hox: homeoticcomplex. A cluster ofhomeodomaintranscription factorsrequired to specifythe identity of bodysegments along theAP body axis ofarthropods and otheranimals

Homeosis: thetransformation of thenormal identity of ananatomical structureor body segment toanother’s identity.Homeosis is usuallyconsidered in thecontext of mutationsin developmentalregulatory genes.Homeotic,regulatory mutationsin these genes havealso been proposedas a factor in someinstances of bodyplan evolution

nal segments of millipede-like ancestors fol-lowed by “haltere-promoting” genes whichsuppressed the second pair of wings of four-winged ancestors. If evolution indeed pro-ceeded in this way, then mutations in thelatter group of genes should produce four-winged flies and mutations in the formergroup, flies with extra legs. (57)

This evolutionary scenario described byLewis has not been borne out quite as heenvisioned it—rather than the evolution ofnew genes, the evolution of regulatory inter-actions appears to have been key to body planchanges. As we discuss below, the details ofHox expression domains and timing, as wellas the target genes controlled by specific Hoxgenes, have been associated with greater andlesser aspects of body plan evolution in a rangeof arthropod groups.

Several excellent reviews covering differ-ent aspects of Hox genes and their con-nections to arthropod evolution have beenpublished in recent years (8, 47, 69). Thesearticles have emphasized the commonalitiesand themes seen across the arthropods andother animals. Here, we have attempted to or-ganize our discussion in terms of several of themajor novelties in arthropod body plan evo-lution. In the course of this, we revisit some ofthe same topics and update their considerationwith recent data. Principally, we hope to illus-trate the diversity of arthropod morphologyand review developmental genetic data rele-vant to its evolutionary plasticity. With thisin mind, we do not limit ourselves to discus-sions of tagmosis or to the Hox genes. Thesehave been fruitful lines of research, but theyare necessarily just the beginning.

What is the Meaning of the“Body Plan” Concept?

A body plan is a basic pattern of anatomi-cal organization shared by a group of animals(71). However, there is sometimes disagree-ment over what constitutes a body plan. Partof this confusion may be historical, but much

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Tagmosis: thespecialization and/oranatomicalunification ofadjacent bodysegments into“tagma” to facilitatecertain behaviors,often through similarmodification ofappendages. Suchbehaviors mayinclude gatheringsensory information,feeding, locomotionof some sort, gasexchange, orbrooding

of it doubtlessly stems from ambiguity inher-ent in the term. The first such conceptualgrouping based on anatomy was the archetypedefined by Richard Owen, who also estab-lished the more enduring idea of homology.An archetype was envisioned as all the possi-ble variations upon an anatomical theme (64).However, in rejecting Darwin’s theory of evo-lution by natural selection, Owen’s archetypenever addressed the relationships betweendistinct morphologies. In 1945, Joseph HenryWoodger first proposed the bauplan (literally a“structural” or “building” plan) as the collec-tion of homologous anatomical features seenacross the natural history of a group (70). Thisrecast Owen’s idea in an evolutionary context,and became translated as “body plan.” Theterm is still sometimes erroneously used todenote an anatomical grade of organization.However, body plans remain a useful conceptbecause they summarize a collection of an-cestral and synapomorphic characters withina group, while accepting their various deriva-tions, and asserting an implied hypothesis thatthese similarities appear due to the mono-phyly of the group.

Given this definition, where is it appro-priate to apply the concept? Does it only ap-ply at greater levels of classification, such asphyla? Can we speak of the arthropod or chor-date body plans, but not apply the term tothe anatomy of insects or tetrapods? We sug-gest that a useful concept should not be artifi-cially limited, and see no problem in speak-ing of the body plan of any presumptivelymonophyletic group sharing a characteristicanatomy. It should be possible to consider“greater” or “lesser” levels of body plans. In-deed, this seems appropriate, given that signif-icant morphological innovation has appearedwithin many phyla since their appearancein the Cambrian, and these may be no lesssignificant to their natural history. Fitch &Sudhaus have made a similar argument basedon changes in the body axes of nematodegroups (35). Other examples of such innova-tions include the evolution of jointed limbsin sarcopterigid vertebrates, the appearance

of wings in pterygote insects, and the lossof segmentation in higher mollusks. There-fore, body plans may be related by degrees tosynapomorphies seen within any clade.

What Defines the Arthropod BodyPlan?

The arthropods have traditionally been de-fined as segmented, appendage-bearing pro-tostomes, protected by a cuticle that is pe-riodically shed with growth (22). They arefurther distinguished from related groups,such as the onychophorans and tardigrades,by the fact that the appendages consist ofpodomeres with separate musculature andinnervation (82). The specialization and/oranatomical unification of adjacent body seg-ments, or tagmosis, helps to facilitate certainbehaviors and varies greatly among arthro-pod groups. Tagmosis may also have followedconvergent patterns along separate arthropodlineages, and several recent studies, based onmolecular sequences and cladistic treatmentsof morphology, have questioned traditionalarthropod groups, such as the Uniramia (54),Mandibulata (49), and Hexapoda (62). It hasalso fueled much debate over the phyloge-netic relationships and monophyly of the ex-tant arthropod classes (20, 21, 49, 73, 103).We frame our discussions in what we favoras the least controversial and most consen-sual of these phylogenies (20, 37, 72), summa-rized in Figure 1. Our favored phylogenetichypothesis of arthropod relationships groupsthe insects, crustaceans, and myriapods intothe Mandibulata. This group is unified bymouthpart homologies, and excludes thechelicerates.

DEVELOPMENTAL GENETICSOF ARTHROPOD TAGMOSIS

Evolution of the Arthropod Head

The union of anterior body segments intoa well-developed head characterizes many ofthe extant arthropod groups. This presumably

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provides the advantages of gathering the sen-sory and feeding appendages at the forwardend of these active animals. Cephalizationseems to have been associated with the re-cruitment of posterior segments into the head,coupled with a reduction of anterior seg-ments. A recent morphological study by Budd(23) examined the head anatomy of severalfossil arthropods in an attempt to address thehomology of the large frontal appendages thatcharacterize fossil crustacean-like species,such as Yohoia and Fortiforceps, as well aslobopods, such as Aysheaia. This phylogeneticstudy included specimens that could be confi-dently assigned as basal members of the Che-licerata and Mandibulata, thereby includingrepresentatives of the extant crown groupswithout the interference of too many mod-ern synapomorphies. In Budd’s analysis, thecrown groups (Mandibulata and Chelicerata)and trilobites formed a well-supported cladethat includes fossil species lacking the frontalappendages, such as Emeraldella and Cam-bropachycope. Based on this and other anatom-ical data, he suggests that the labrum seen inMandibulata and Chelicerata may be evolu-tionarily derived from the frontal appendage.This is consistent with the expression of ap-pendage patterning genes in the labrum (41)and with their functional requirement forproper labral development in insects and che-licerates (9, 80).

Hox Genes and Tagmosis

From genetic studies in Drosophila, Hox geneshave been well characterized as high-levelregulatory transcription factors, which act toimpart specific identities upon the body seg-ments and other structures in which theyare expressed (reviewed in 47). In certain in-stances, the overlap of two or more Hox genescan produce fates distinct from those speci-fied by either gene alone. For example, in theDrosophila labial imaginal disc, pb and Scr in-teract to direct proboscis development, wherealone these genes specify only maxillary palpor leg (2). Therefore, the 10 ancestral arthro-

TAGMOSIS IN MAJOR ARTHROPODGROUPS

Insects are the most tagmatically consistent arthropod class.They bear a head of fused segments, a thorax of three seg-ments, followed by an abdomen of 10 or 11 segments.

The myriapods possess a well-organized head, similar tothat of insects, followed by a varying number of homonymoustrunk segments. Chilopoda (centipedes) bear one pair of legson each trunk segment, while Diplopoda (millipedes) bear twopairs of legs on most segments. Pauropoda represent a curiousintermediate state, where a segment as seen from the dorsalside spans what are apparently two segments ventrally.

Presumably, basal crustaceans consist of head and trunktagmata. Among Malacostraca, the body plan consists of threetagmata: cephalon, pereon, and pleon. The appendages of thepereon and pleon are usually divided functionally to tasks suchas walking, swimming, respiration, or brooding eggs, but thesetasks do not always fall to the same tagma in different groups.

The basal chelicerates possess a body plan organized intothree tagmata: prosoma, mesosoma, and metasoma. The pro-soma bears the mouthparts and legs, whereas the meso-soma bears respiratory appendages. Arachnids have apparentlyeliminated the metasoma (16), and consist of two tagmata:prosoma and opisthosoma.

pod Hox genes are theoretically capable ofspecifying at least 20 unique body regions.(Assuming colinearity, if each Hox gene hasan area where it is uniquely expressed andanother in overlap with its neighbors, 2n-1 regions can be demarcated. An anteriorHox-free region adds one additional possibleidentity.) It is possible that such extensive dif-ferentiation exists within the central nervoussystem, but this has not been carefully exam-ined. However, in the embryonic ectodermof most arthropods, several Hox genes typi-cally overlap in a given segment, such that farfewer than the theoretical maximum numberof body regions is initially distinguished.

What is usually observed is a correla-tion between the tagmatic boundaries of anarthropod’s body plan and the overlap of Hoxgenes in that region (Figure 1). For example,in arachnids (7, 31, 86), lab, pb, Hox3, Dfd,

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Scr, and Hox6 are expressed in a nested pat-tern within the prosoma, where they overlapbroadly. Similarly, in the opisthosoma expres-sion of Antp, Ubx, abd-A, and Abd-B ortho-logues also overlap in a nested manner. In theMandibulata, a distinct head usually gathersseveral pairs of appendages, which performseparate gnathal functions. This reaches anextreme in the decapod crustaceans, whichmay have as many as seven pairs of appendages

that function in feeding. In these arthropods,the Hox genes overlap very little in the head(5, 46, 47). It seems likely that this facili-tates the specification of a greater numberof distinct identities, although this has onlybeen tested functionally in a handful of insectspecies.

Nevertheless, it is relatively uncommonfor Hox genes to cross a tagmatic boundary.This is most clearly seen in the arachnids,

100 Angelini · Kaufman

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where segments of the prosoma and opistho-soma express separate sets of Hox genes.Only the Antp orthologue shows a small de-gree of crossover into the L4 prosomal seg-ment, while it is predominantly expressed inthe opisthosoma. In myriapods, the trunk ischaracterized by the expression of Ubx andabd-A (46). Again, Antp is the only Hox gene tocross this tagmatic boundary, although unlikeits pattern in chelicerates, in the centipede it ispredominantly expressed in the maxillipedialsegment and tapers off posteriorly into thetrunk. In the insects, Antp and abd-A chieflyspecify the thorax and abdomen, respectively.

Among different crustacean body plans,the Hox genes of the trunk correlate in expres-sion with tagmosis. Brachiopod crustaceanshave a homonymous trunk, and in the bra-chiopod Artemia franciscana, Antp, Ubx, andabd-A overlap extensively in their expres-sion (11). However, in the decapod Procam-barus clarkii (5) and the isopod Porcellio scaber(4), expression of Antp and Ubx is restrictedto the pereon, while abd-A expression ap-pears in the pleon. Therefore, the boundariesof these tagmata are respected by the Hoxgenes.

T1: first thoracicsegment orprothorax

So, does the overlap of Hox genes provide amolecular definition of tagmata? Not reliably,it appears. There are many instances whereHox expression crosses tagmatic boundaries,often at later stages of development to modifythe fate of individual segments within a tagma.For example, in later stages of Drosophila em-bryogenesis, Scr and Ubx expression expandfrom neighboring tagmata into T1 and T3,respectively, to modify their identities. As isdiscussed below, these domains of expressionlikely evolved in connection with the place-ment and specialization of wings on the insectbody plan.

The Recruitment of Maxillipeds inCrustacea

Hox genes are known to specify segment iden-tity in Drosophila, alone or in combination.However, viewed from an evolutionary per-spective, do Hox genes act passively to spec-ify the identity of segments, or can they playan instructive role? In other words, how easilycan modules of effector genes come under theregulation of different Hox genes or combi-nations of Hox genes? If Hox genes were to

←−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−Figure 1The four most commonly recognized arthropod classes differ in body plan and Hox gene expression. Aconsensus tree of major arthropod groups is shown here. This tree is not meant to be exhaustive, andnumerous taxa have been omitted. For each class, a representative of the most well-examined body plan isshown. The consensus patterns of Hox gene expression are also shown for these representative groups.Body segments and the appendages they typically bear are abbreviated. For segments: Oc, ocular; Ch,cheliceral; Pd; pedipalpal; L1, etc., first leg-bearing, etc.; O1, etc., first opisthosomal, etc.; An1, etc., firstantennal, etc.; In, intercalary; Mn, mandibular; Mx1, etc., first maxillary, etc.; Mxp, maxillipedial; T1,etc., first thoracic, etc., P1, etc., first pereonic, etc.; p1, etc., first pleonic, etc.; A1, etc., first abdominal,etc. Appendage abbreviations: lbr, labrum; chel, chelicerae; pedi, pedipalps; ant, antennae; man,mandibles; max, maxillae; mxp, maxillipeds; plpd, pleopods; gen, genitalia. The Holometabola includeinsect orders with true metamorphosis. Hemimetabolous pterygote insects comprise the Paraneoptera,which includes Hemiptera and allied orders, and the Polyneoptera, which includes Orthoptera,Phasmatodea, and others. Apterygote insects are a paraphyletic assemblage that includes the firebratThermobia (Zygentoma). Malacostracan crustaceans include the isopods, decapods, and the “trueshrimp.” Maxillopoda and Brachiopoda are diverse and possibly paraphyletic groups. Remipedia includesthe barnacles and related crustaceans. Myriapoda includes Chilopoda (true centipedes), Symphyla(garden centipedes), Diplopoda (millipedes), and Pauropoda. The chelicerates are considered to be basalamong the arthropods. Arachnida includes most extant chelicerates, including the Araneae (spiders),Acari (mites), as well as scorpions and others. The Xiphosura include extinct chelicerates as well as extanthorseshoe crabs of the genus Limulus. The extinct trilobites are likely a basal lineage withinChelicerata.

www.annualreviews.org • Arthropod Body Plan Evolution 101

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JOURNAL OF EXPERIMENTAL ZOOLOGY (MOL DEV EVOL) 285:19�26 (1999)

© 1999 WILEY-LISS, INC.

Why Do Almost All Mammals Have Seven CervicalVertebrae? Developmental Constraints, Hox Genes,and Cancer

FRIETSON GALIS*Institute for Evolutionary and Ecological Sciences, University of Leiden,2300RA Leiden, The Netherlands

ABSTRACT Mammals have seven cervical vertebrae, a number that remains remarkably con-stant. I propose that the lack of variation is caused by developmental constraints: to wit, changesin Hox gene expression, which lead to changes in the number of cervical vertebrae, are associatedwith neural problems and with an increased susceptibility to early childhood cancer and still-births. In vertebrates, Hox genes are involved in the development of the skeletal axis and thenervous system, among other things. In humans and mice, Hox genes have been shown also to beinvolved in the normal and abnormal (cancer) proliferation of cell lines; several types of cancer inyoung children are associated with abnormalities in Hox gene expression and congenital anoma-lies. In these embryonal cancers the incidence of a cervical rib (a rib on the seventh cervicalvertebra, a homeotic transformation of a cervical vertebra towards a thoracic-type vertebra) ap-pears to be increased. The minimal estimate of the selection coefficient acting against these muta-tions is about 12%.

In birds and reptiles variations in the number of cervical vertebrae have frequently occurredand there is often intraspecific variability. A review of the veterinary literature shows that cancerrates appear lower in birds and reptiles than in mammals. The low susceptibility to cancer inthese classes probably prevents the deleterious pleiotropic effect of neonatal cancer when changesin cervical vertebral number occur.

In mammals there is, thus, a coupling between the development of the axial skeleton and otherfunctions (including the proliferations of cell lines). The coupling of functions is either a conservedtrait that is also present in reptiles and birds, but without apparent deleterious effects, or thecoupling is new to mammals due to a change in the functioning of Hox genes. The cost of thecoupling of functions in mammals appears to be an increased risk for neural problems, neonatalcancer, stillbirths, and a constraint on the variability of cervical vertebral number. J. Exp. Zool.(Mol. Dev. Evol.) 285:19�26, 1999. © 1999 Wiley-Liss, Inc.

The exceedingly low level of interspecific varia-tion in the number of cervical vertebrae of mam-mals has puzzled biologists for more than 150 years.In birds, reptiles, and amphibians the number ofcervical vertebrae varies considerably, and in mam-mals the number of vertebrae in other vertebralregions is variable as well (Lebouck, 1898; Schulz,�61). Swans� long necks have a striking 22�25 cer-vical vertebrae, while ducks have 16 (Woolfenden,�61), and swifts 13 (Starck, �79). Giraffes and drom-edaries, however, have only seven vertebrae (Fig.1), as do the Dugong (Fig. 2) and whales with theirshort necks (Starck, �79). There are only three gen-era with an exceptional number of cervical verte-brae, manatees (Trichechus) and sloths (Bradypusand Choloepus). Thus, there seems to be an evolu-tionary constraint towards the development of vari-ability in the cervical region in mammals.

Intraspecific variations in the number of cervi-cal vertebrae in mammals are extremely rare,whereas intraspecific variations in the number ofmore caudal vertebrae are common, especially ofthe lumbar, sacral, and coccygeal regions (e.g.,Lebouck, 1898; Schulz, �61). However, one varia-tion of cervical vertebrae does occur infrequently:cervical ribs. A cervical rib is on the seventh cer-vical vertebra, is a partially or wholly homeotictransformation of the seventh cervical vertebrainto the first thoracic vertebra and, thus, reducesthe number of cervical vertebrae (and increases

*Correspondence to: Frietson Gailis, Institute for Evolutionary andEcological Sciences, University of Leiden, PO Box 9516, 2300RALeiden, The Netherlands. E-mail: Galis@rulsfb.leidenuniv.nl

Received 28 October 1998; Accepted 16 December 1998.

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20 F. GALIS

the number of thoracic vertebrae). Further studyof this naturally occurring variation seems rel-evant with respect to the evolutionary constrainton cervical vertebral number, and more specifi-cally, to the study of the selective factors againstthis variation.

PATHOLOGIES ASSOCIATED WITHCERVICAL RIBS

Consideration of the pathologies in humans thatare associated with cervical ribs reveals two types,thoracic outlet syndrome (TOS) and early childhoodcancer. TOS involves pressure on the nerves of thebrachial plexus and on the subclavian artery, some-times leading to severe degenerative symptoms inthe arm (Fig. 3; Makhoul and Machleder, �92; Roos,�96). Often surgery is performed to relieve symp-

toms. Research on this syndrome has revealed thatcervical ribs are invariably associated with changesin the brachial plexus (a different contribution ofmotor and sensory nerves to the brachial plexus)and other structural abnormalities (Makhoul andMachleder, �92; Roos, �96). The correlation ofsymptoms must be due to mutual influences ofthe notochord, neural tube, neural crest, andsomites at the time of somite formation (Gosslerand Hrabe de Angelis, �98).

Early childhood cancer is a considerably moreserious pathology. Childhood cancers tend to re-sult from aberrant developmental processes andare generally embryonal in origin. They are asso-ciated with a high incidence of congenital abnor-malities. This association is assumed to be causedby a common underlying genetic abnormality

Fig. 1. Skeleton of a dromedary (Camelus dromedarius). Note the large cervical verte-brae. From Owen (1866).

Fig. 2. Skeleton of a dugong (Dugong dugon). Note the small cervical vertebrae. FromOwen (1866).

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CERVICAL VERTEBRAE: HOX GENES AND CANCER 21

(Schumacher et al., �92; Anbazhagan and Raman,�97). A high incidence of vertebral anomalies, es-pecially cervical ribs, was found in a study spe-cifically devoted to finding vertebral anomalies,of 750 children with embryonal cancers (Schu-macher et al., �92). An incidence of around 25% cer-vical ribs was found for the following embryonalcancers: neuroblastoma, brain tumour (astrocytomaand medulloblastoma), acute lymphoblastic andmyeloid leukemia, soft tissue sarcoma, Wilms� tu-mour and Ewing sarcoma (Table 1). This findingconfirms the observations by Adson and Coffey(�27), who found that cervical ribs are sometimesdiscovered in children because of the presence ofa tumor in the neck. In addition, a high correla-tion between malformations of ribs (without fur-ther specification) and cancer of all types wasfound in a large study on childhood cancers (Narodet al., �97).

In agreement with the hypothesis of a commongenetic abnormality underlying both early child-hood cancer and cervical ribs is the observationthat the relation between congenital anomaliesand cancer is stronger in infants than in olderchildren (Brodeur, �95; Breslow et al., �96; Gurneyet al., �96). Many infants with cancer demonstrate

unique epidemiologic, clinical, and genetic char-acteristics compared with cancers that occur inolder children. Some of the early onset cases arefamilial cases, which are rare and generally char-acterized not only by an early onset, but also by aworse prognosis (Brodeur, �95; Breslow et al., �96;Gurney et al., �96). This phenomenon is explainedby Knudson�s (�84) model for embryonal childhoodcancers in which two (or only a few) mutationalevents occur before the onset of cancer. In famil-ial cases one of these mutations has occurred inthe germ line and is transmissible to the offspring.The germ-line mutation has been identified forfamilial retinoblastoma (reviewed in Brodeur, �95).The timing of mutational events should influencethe incidence and type of congenital anomaly andthese differences in timing can, thus, explain thatnot all cases of childhood cancer have congenitaldefects and that the anomalies are variable.

THE ROLE OF HOX GENES INPATTERNING OF THE SKELETAL AXIS

AND IN CELL PROLIFERATION

Hox genes play an important role in the pat-terning of the axial skeleton in all vertebrateclasses (Krumlauf, �94). Hox gene mutants display

Fig. 3. Illustration of the thoracic outlet in a person witha cervical rib showing how arteries and axons are compressedwhen the m. anterior scalaenus contracts. The cervical rib isincomplete and fused with the first thoracic rib. (Reproduced

by permission from Adson AW. 1947. Surgical treatment forsymptoms produced by cervical ribs and the scalenus anticusmuscle. Surg Gynecol Obstet 85:687�700.)

TABLE 1. The incidence of a cervical rib in children with embryonal cancers1

Type of childhood cancer Number of cases Incidence of a cervical rib

Neuroblastoma 88 33%Brain tumour 234 27.4%Leukemia 227 26.8%Soft tissue sarcoma 98 24.5%Wilms tumour 68 23.5%Ewing sarcoma 35 17.1%1Data from Schumacher et al. (�92).

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22 F. GALIS

abnormalities of the vertebral column. Particu-larly common phenotypic abnormalities in micemutants are cervical ribs. At least four knock-outmutants of hox genes in mice have an increasedincidence of cervical ribs (Hoxa-4, Hoxd-4, Hoxa-5 and Hoxa-6) (reviewed in Horan et al., 95). Inaddition, transgenic mice overexpressing Hoxb-7or Hoxb-8 and mice mutants lacking the polycomb-group genes bmi-1 and mel-18 (involved in theregulation of Hox genes) display cervical ribs(McLain et al., �92; Charité et al., �94; Akasaki etal., �96; van der Lugt et al., �96). Thus, the forma-tion of cervical ribs is a process that seems to beparticularly susceptible to perturbations in Hoxgene expression (Horan et al., �95). Most of thesemutant mice have a severely impaired viability.

At the same time Hox genes have been shownto be involved in the proliferation of cell lines inmice and humans (e.g., Corte et al., �93; Lawrenceet al., �96; Anbazhagan et al., �97). In a study inwhich cells of the myeloid, macrophage, erythroid,and B- and T-lymphoid lingeages were investi-gated for expression of homeotic genes, up to 20different Hox genes were found to be activated(Kongsuwan et al., �88). Some of the genes wereubiquitously expressed, while others were re-stricted to particular cell lineages or lines (see alsoLawrence et al., �96). When the cells were inducedto differentiate, the pattern of Hox gene expres-sion changed. Changes in Hox gene expressionhave been demonstrated for several types of can-cer, including some childhood cancers that werefound to have a high incidence of vertebral anoma-lies: neuroblastoma, Wilms� tumour, and leukemia(Corte et al., �93; Lawrence et al., �96; Manohar etal., �96; Anbazhagan et al., �97). The coupling be-tween these two functions of Hox genes is clearlydemonstrated in mice with mutations of thePolycomb- and trithorax-group genes (Pc-G andtrx-G genes). The evolutionary-conserved Pc-G andtrx-G genes are involved in the maintenance ofexpression of homeobox genes including Hom andHox genes. Mice lacking or overexpressing Pc-Gand trx-G genes have altered expression areas ofHox genes and display both vertebral anomalies(including cervical ribs and other changes in thenumber of cervical vertebrae) and leukemia or re-lated cancers (Corte et al., �93; van der Lugt et al.,�94; Yu et al., �95; Akasaki et al., �96; Schumacheret al., �96; Coré et al., �97). One of these genes is thetrx-G gene Mll, the most commonly involved genein infant leukemias (Pui et al., �95). Mice heterozy-gous for the knock-out allele of the caudal geneCdx2, which is involved in the regulation of Hox

genes (Epstein et al., �97), also display both ver-tebral abnormalities and a predisposition for in-testinal cancer (He et al., �97). Furthermore,rostral overexpression of Hoxb-8 leads to cervicalribs in mice, whereas overexpression in bone mar-row is associated with leukemia (Perkins andCory, �93) and overexpression in fibroblasts withfibrosarcoma (a cancer) (Aberdam et al., �91).

Thus, in mammals Hox genes are involved inpatterning of the skeletal axis and in the prolif-eration of cell lines (among other functions) andaberrations in the regulation of Hox genes maylead to abnormalities in both these functions.

Selection against cervical ribs

The occurrence of cervical ribs in various mam-malian species and the particularly frequent occur-rence of cervical ribs in experimental mice mutantsindicate that there is not a lack of genetic variationfor this phenotype. Thus, there must be strong sta-bilizing selection against the establishment of thistrait. The correlated incidence of cervical ribs andchildhood cancer presents a strong case for ap-parent selection against cervical ribs due to del-eterious pleiotropic effects. This correlation isstrengthened by the mice mutants that not onlydisplay variations in cervical vertebral number, butalso have cancer and a much reduced fitness(Akasaki et al., �96; van der Lugt et al., �96;Schumacher et al., �96; Coré et al., �97; He et al.,�97). The incidence of cervical ribs in the generalhuman population averaged over several large stud-ies (Adson and Coffey, �27; Etter, �44; Sycamore, �44;Crimm, �52; Menárguez Carretero and CampoMuñoz, �67) is approximately 0.2% (347 cases outof 220,026; percentages varied from 0.03�0.5). Thefrequency of these embryonal cancers added to-gether in the U.S. and Europe is approximately0.1% (0.01% Wilms� tumour (15), 0.033�0.075% leu-kemia (Stiller and Parkin, �96), 0.014% neuroblas-toma (Gurney et al., �96); braintumours 0.02�0.06%).

Assuming a chance for embryonal cancers of 0.1%and a chance for cervical ribs associated with em-bryonal cancers of 25% (Shumacher et al., �92) im-plies a 0.025% chance for children to have both acervical rib and early childhood cancer. Assuming afrequency of cervical ribs of 0.2% in the generalpopulation after early childhood and an average sur-vival of 60% for early childhood cancers (Miller etal., �95) implies that the total incidence of cervicalribs at birth is 0.21%, of which 11.9% will developan embryonal cancer. This suggests that childrenwith embryonal cancers have a 125-fold increasedincidence of cervical ribs (25% vs. 0.2%), and that

15

CERVICAL VERTEBRAE: HOX GENES AND CANCER 23

children born with a cervical rib have an almost120-fold chance of early childhood cancer (11.9% vs.0.1%). Thus, neonatal cancer alone seems to presentsufficient apparent selection against the establish-ment of cervical ribs.

In addition, the symptoms of TOS will enhancenatural selection against cervical ribs by directstabilizing selection. The seriousness of the symp-toms is correlated with the amount of manuallabour that is being performed. Therefore, undernatural circumstances the selective disadvantagewill be larger than in the sheltered present-dayhuman environment. Adults with a rudimentaryfirst rib (a partial transformation towards eightcervical vertebrae) often have TOS, suggestingnatural selection against this variation in cervi-cal vertebral number as well (Gelabert et al., �97).

A further selection factor against cervical ribscould be an increased chance of stillbirths. A largeminority (>30%) of fetuses between 49 and 150 mmhas ossification centers in the seventh cervicalprevertebra (Peters, �27; Noback, �51; Meyer, �78).These ossification centers appear in the same posi-tion as those of thoracic prevertebrae�s future ribs.An explanation of this phenomenon could be thatthe high percentage of ossification centers (cervicalribs) is related to the causes that have led to thepremature death of these fetuses. Again the inter-active nature of the early processes which involveHox genes may present a link between cervical ribsand other abnormalities, as it is unlikely that theossification centers themselves cause stillbirths. Itis possible that the problems in the proliferation ofcell lines that lead to neonatal cancer are also caus-ally related to the stillbirths.

A COMPARISON OF MAMMALS,REPTILES AND AMPHIBIANS

The number of cervical vertebrae is variable inamphibians, reptiles, and birds, in strong contrastto mammals (in fishes no cervical vertebral re-gion is distinguished). The selection against suchvariation in the number of cervical vertebrae mustbe considerably weaker or absent in these othervertebrate classes. In necropsy studies of zoo ani-mals, cancer rates of birds and reptiles are lowcompared to mammals (Fox, �12; Ratcliffe, �33;Ippen, �59; Lombard and Witte, �59; Effron et al.,�77). The low susceptibility to cancer in reptilesmakes intuitive sense because of their low meta-bolic rate, which leads to an expectation of lowoxidative DNA damage (cf. Adelman et al., �88;Perez-Campo et al., �98). The low susceptibility inbirds may seem surprising given their high meta-

bolic rate (McNab, �88; Ricklefs et al., �96). How-ever, there is evidence (from canaries and pigeons)that birds have a remarkably low free radical pro-duction and, thus, a low amount of oxidative dam-age (Perez-Campo, �98).

In addition, cancer in birds, especially in youngbirds, is generally believed in the majority of casesto be induced by viruses (Effron et al., �77; Reece,�96; Misdorp and Kik, personal communication).In mammals viral cancers are estimated to occurin 15% of cases, mainly liver cancer, cervical can-cer, and Hodgkin�s disease in children (Pisani etal., �97). A survey of 343,600 young chickensshowed that none developed a non-virally associ-ated cancer in the first five weeks of life whereas53 developed a virally associated cancer (Helmsley,�66). This pattern, confirmed by Reece (�96), is instriking contrast to that in human infants wherein the first month of life almost all cancers are non-virally associated embryonal cancers, predomi-nantly neuroblastoma (35%; Gurney et al.,�96).

In reptiles the viral induction of cancer has beenstudied much less. However, reptilian cancersseem more similar to cancers in birds than inmammals (Effron et al., �77) and the viruses thatinduce cancer in reptiles also seem more similarto those in birds than in mammals (Trubcheninovaet al., �77). In addition, reptiles with cancer atnecropsy are usually very old, and one study hasshown that snakes with cancer are even older onaverage than snakes without cancer (Ramsay etal., �96). In amphibians the situation is even lesswell documented; however, the one type of cancerthat is well documented, Lucké�s tumour in Ranapipiens, is a virally induced cancer (McKinnell andCarlson, �97).

There are a few mammalian species with an ab-errant number of cervical vertebrae: manatees andsloths. Sloths especially show a spectacular break-down of the constraint on variation as the num-ber of cervical vertebrae varies from 6 to 9 (Giffinand Gillett, �96). There is no explanation for theseexceptions, but I suggest as hypothesis that theextremely low metabolic rate of manatees andsloths (e.g., McNab �88; Gallivan and Best �89;Koteja �91; Hammond and Diamond, �97) is asso-ciated with low oxidative DNA damage and, thus,with a low susceptibility to cancer (Adelman etal., �88; Shigenaga and Ames, �93). This hypoth-esis needs to be tested.

CONCLUSIONS

It appears, therefore, that the cause of the con-servation of seven cervical vertebrae should be

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24 F. GALIS

sought (1) in a genetic link between early child-hood cancer and stillbirths and variation in cer-vical vertebrae number, and (2) in the neuronalproblems leading to the thoracic outlet syndromein adults associated with cervical ribs. The in-volvement of Hox genes in the cancers that areassociated with cervical ribs in mice and menpoints to a coupling between functions of Hoxgenes that appears to be lacking in birds, reptiles,and amphibians, or at least has no apparent con-sequences when cervical vertebral number ischanged. There are two possible explanations forthe observed coupling in mammals: (1) the cou-pling of functions of Hox genes has newly ap-peared in mammals due to a change in thefunctioning of Hox genes (e.g., a new function inproliferation in mammals); and (2) the couplingof functions was already present in reptiles, buthidden because of the low susceptibility to can-cer. This coupling has only become detectable inmammals because of an increase in susceptibilityto cancer. And this increase in cancer susceptibil-ity can be the direct result of the increase in meta-bolic rate, which is associated with an increase inoxidative damage (Adelman et al., �88; Shigenagaand Ames, �93).

The increase in cancer susceptibility and thepresumed increase in stillbirths are pleiotropicdeleterious effects, whereas the neuronal prob-lems are a direct consequence of the change incervical vertebral number. The fact that the pleio-tropic effect of cancer recurs for what presum-ably are a large number of different mutationsallows us to classify these collectively as a devel-opmental constraint. To further understand theconstraint on changes in the number of cervicalvertebrae that exists in virtually all mammals, astudy of the function of Hox genes in cell prolif-eration and carcinogenesis in birds, reptiles, andamphibians is urgently needed. Furthermore, itshould be an interesting experiment to select forcomplete cervical ribs in a mammalian species tosee whether a healthy strain can be produced, orwhether this would lead to the predicted increasein susceptibility for cancer, stillbirths, and neu-ronal problems.

ACKNOWLEDGMENTS

I thank Hans Metz, Rogier Versteeg, GünterWagner, Jacques van Alphen, and Adam Wilkinsfor stimulating discussions and ideas, and MajaKik, Elliott Jacobson, Hans Feuth, and ProfessorMisdorp for medical and veterinary information.Russ Lande, Gerard Mulder, Louise Roth, Menno

Schilthuizen, Jan Sevenster, Elisabeth van Ast-Gray, Günter Wagner, Adam Wilkins, Ole See-hausen and an anonymous referee gave manyhelpful comments on the manuscript. Thanks toDavid Povel and Frank Alders for their help incollecting literature and to Adri �t Hooft and Mar-tin Brittijn for help with the figures.

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TRABAJO PRÁCTICO N°2: GUÍA DE PROBLEMAS Problema 1

La evolución de los apéndices es uno de los temas más estudiados bajo una perspectiva

filogenética, de embriología comparada y experimental. En particular dentro de los tetrápodos, los

anfibios son un grupo de gran diversidad en cuanto al número de dígitos y falanges.

Entre los anfibios, existen dos grandes órdenes: los Anuros (ranas) y los Urodelos (salamandras).

Ambos, por lo general, poseen 5 dígitos en sus apéndices posteriores. Diferentes estudios sugieren

que el ancestro de estos dos grupos poseía un apéndice posterior caracterizado por 2 falanges en el

primer dígito, 3 en el segundo, 4 en el tercero, 4 en el cuarto y 3 en el quinto (fórmula del número

de falanges: 23443). Por lo general, las especies de Anuros poseen una fórmula de falanges muy

conservada e igual a 22343 (ver Figura 1). Por el contrario, en los Urodelos la fórmula del número

de falanges es mucho más variable que en los Anuros.

En la Tabla I se esquematiza la secuencia de diferenciación de las falanges durante la ontogenia en dos especies modelo Xenopus laevis y Ambystoma mexicanus, anuro y urodelo, respectivamente. De acuerdo con esta información:

a) Describa brevemente cómo es el desarrollo ontogenético de las falanges en cada especie. b) ¿Qué clases de homologías están implícitas en esta comparación? Defínalas.

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El Dr. Pere Alberch, gran embriólogo evolutivo, abordó de manera experimental el problema de la variación en el número de falanges en los anfibios, tratando con un inhibidor mitótico (colchicina) durante las etapas tempranas del desarrollo de los apéndices posteriores de ambas especies. Como resultado de este experimento se observó una reducción en el número de falanges en los 5 dígitos de cada especie. La información de dicho experimento se resume en las Figuras 1 y 2. c) ¿Encuentra algún patrón que relacione la reducción del número de dígitos con el tiempo de desarrollo de los mismos? Formule una hipótesis que vincule ambos resultados.

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En la naturaleza se puede observar especies de anfibios con 4 dedos, tanto en el orden de los Anuros como en el de los Urodelos. Si este patrón natural concuerda con la hipótesis planteada anteriormente por Ud.: d) ¿El dedo “pulgar” (el primer dígito con falange) de ambas especies es homólogo (primario)? e) Defina los términos alometría evolutiva y alometría ontogenética y proponga un ejemplo de ambos en el caso de estudio.

Problema 2

Buscando recursos para estudiar el módulo de Evolución del Desarrollo, usted se encuentra con los datos de pingüinos del género Pygoscelis, colectados en el archipiélago de Palmer entre el 2007 y el 2009 (Gorman et al. 2014). Estos datos contienen, entre otras medidas, el alto del pico (en milímetros) y la masa corporal (en gramos) de 333 especímenes pertenecientes a tres especies: Pygoscelis adeliae, P. antarctica y P. papua. A fin de explorar posibles alometrías, usted calcula y grafica el valor promedio del alto del pico y la masa corporal de cada especie:

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a) Interprete el gráfico de la derecha. ¿Qué tipo de alometría representa la línea gris punteada?

Describa brevemente la relación entre tamaño y altura del pico implicada en esta figura.

A continuación, usted añade al gráfico los datos individuales de los 333 especímenes adultos, diferenciando por especie.

b) ¿Qué tipo de alometría representan las líneas continuas?

c) ¿Considera que la relación alométrica intraespecífica se encuentra preservada a lo largo de la

evolución de estas especies?

d) ¿Considera que la relación alométrica intraespecífica de cada especie podría haber sido predicha utilizando solo la información del primer gráfico?

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Finalmente, identifica el sexo de cada espécimen y obtiene el siguiente gráfico (los símbolos vacíos representan los machos y los llenos representan las hembras):

Usted se ha percatado de que, en general, las alometrías se utilizan para describir de manera aproximada el cambio de forma a lo largo del crecimiento. e) ¿Considera que la ontogenia es el proceso subyacente responsable de la relación alométrica que presenta cada especie de pingüino, o existe otro fenómeno biológico que permita explicarla de manera más satisfactoria?

Problema 3

Relacione cada uno de los siguientes gráficos con uno de los enunciados a continuación. Justifique sus respuestas. a) El estudio comparado de las alometrías a nivel craneofacial no permite inferir procesos heterocrónicos dado que en la muestra se hallan subrepresentados algunos estadios ontogenéticos de ambas especies. También se sospecha que una de las muestras ontogenéticas incluye ejemplares de más de una especie. b) Un proceso heterocrónico de tipo pedomórfico actuó a nivel craneofacial en humanos mientras que no se puede postular un cambio en los tiempos de desarrollo de dichas estructuras en chimpancés. c) La relación entre la forma del neurocráneo y la forma de la cara en humanos presenta un desarrollo desacelerado desde la adolescencia a la adultez con respecto a estadios anteriores de su ontogenia. d) El estudio de las alometrías a nivel craneofacial no permite inferir procesos heterocrónicos en la divergencia entre los linajes de humanos y chimpancés. e) Nuestra especie se caracteriza por una acentuada aceleración de los ritmos de desarrollo.

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Problema 4

Los amonoideos (Figura 1A), extintos desde hace 65 millones de años, fueron moluscos

nadadores con conchillas en espiral similares a los Nautilus actuales, que dominaron las asociaciones

de invertebrados nectónicos durante el Mesozoico. A fin de explorar la variación morfológica de

este grupo, Raup (1967) graficó 405 especies a lo largo de dos ejes morfológicos: W (la tasa de

expansión de las vueltas de la espiral) y D (la distancia de la apertura de la conchilla al eje de la

espiral). En primer lugar, sus resultados mostraron que, aunque las distintas especies presentan una

variedad de formas, la mayoría tiende a agruparse alrededor de un pico de D~0.34 y W~2 (Figura

1B). En segundo lugar, observó que existe una región “prohibida”, la cual corresponde a los valores

de W>1/D, límite que es apenas atravesado por muy pocas especies. Dentro de dicha región, las

vueltas de los amonoideos no se superponen entre sí, mientras que por fuera de este límite

presentan distintos grados de superposición (Figura 1D).

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Intrigado por esta distribución de las morfologías Chamberlain (1976) realizó experimentos de

desempeño hidrodinámico a partir de diferentes conchillas con morfologías sintéticas. Los

resultados se presentan en la Figura 1C. Chamberlain descubrió que las conchillas con vueltas

superpuestas poseen un coeficiente de arrastre menor y por lo tanto representan nadadores más

eficientes que aquellas cuyas vueltas no están en contacto. También observó que el pico

morfológico identificado por Raup se corresponde aproximadamente con formas que tienen un

arrastre particularmente bajo, y por lo tanto nadadores particularmente eficientes. Sin embargo,

también descubrió que existe una segunda morfología con arrastre mínimo y capacidad natatoria

elevada, correspondiente a valores de D~0.1 y W~1 (Figura 1C, izquierda), que no se encuentra

ocupada por ninguna de las 405 especies estudiadas por Raup (Figura 1C, izquierda).

En base a estos resultados, ¿Qué tipo de restricciones identifica? Justifique.

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Problema 5

Adams y Nistri (BMC Evolutionary Biology 2010) estudiaron la morfología de las patas de

ocho especies de salamandras europeas del género Hydromantes para poner a prueba la hipótesis

de que la morfología del adulto constituye una adaptación relacionada con sus hábitos arborícolas.

Estos autores observaron que cinco especies habitantes de la isla de Cerdeña alcanzan un tamaño

mayor que las otras tres especies pertenecientes al continente. Sin embargo, todas las especies

muestran valores similares y relativamente bajos de sinuosidad lo que implica la presencia de más

tejido interdigital (Figura 1).

Figura 1: Esquemas de la pata de las salamandras estudiadas que

muestran la mayor sinuosidad y menor presencia de tejido interdigital en

individuos pequeños (a la izquierda) en comparación con individuos

grandes (a la derecha).

Cuando estos autores analizaron la morfología a lo largo del desarrollo de cada especie,

encontraron patrones muy diferentes (Tabla 1). Por un lado, la mayoría de la especies no mostró

cambios en el nivel de sinuosidad (o en la abundancia de tejido interdigital) a través de la ontogenia.

Por otro lado, en tres especies habitantes de la isla, se observó que el nivel de sinuosidad disminuye

(o que la cantidad de tejido interdigital aumenta) a medida que los animales crecen.

a) Interprete los resultados de la Tabla 1. Identifique el/los tipo/s de alometría/s analizados.

Tabla 1: Principales resultados de los

análisis de regresión de la sinuosidad

versus el tamaño total. Para cada

especie se muestra el valor de la

pendiente de la recta de regresión y

la significación asociada. p < 0,05

indicado en negrita, c: especie

continental, i: especie isleña.

27

A continuación, para comprender mejor la evolución de las trayectorias ontogenéticas

analizadas, los autores utilizaron una filogenia del grupo y encontraron que el patrón de

independencia entre caracteres es el estado ancestral más probable para el linaje europeo (Figura

2).

b) En base a estos resultados, ¿qué conclusiones puede extraer acerca de la homología del patrón de crecimiento alométrico observado en las tres especies isleñas? ¿Cómo podría explicar estos resultados considerando el concepto de heterocronía?

Posteriormente, se estudió la trayectoria ontogenética de una especie de salamandra

norteamericana (H. platycephalus) la cual exhibe un crecimiento alométrico similar al observado en

las especies isleñas. Cuando se incluyó a H. platycephalus en el análisis, los patrones descriptos

anteriormente no cambiaron pero si lo hizo la condición ancestral de todo el género la cual pasó a

ser alométrica.

c) ¿Modifica este resultado su hipótesis de homología expuesta en el punto anterior? Justifique.

Finalmente, los autores extendieron estos análisis a más especies de salamandras

pertenecientes a otros géneros y observaron que las trayectorias ontogenéticas de las especies

europeas se asemejan, por un lado, a especies que poseen hábitos similares (es decir, especies

trepadoras) y, por otro lado, a especies cavadoras las cuales presentan una posición más basal en la

filogenia de las salamandras.

d) ¿Cómo podría explicar estos resultados en términos de exaptación?

Figura 2: Relaciones filogenéticas de

las especies de salamandras

europeas estudiadas basadas en una

filogenia molecular realizada

utilizando datos de secuencias de

ADN mitocondrial y nuclear. Los

esquemas muestran el patrón de

alometría asociado a cada especie. c:

especie continental, i: especie isleña.

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