... It will be intriguing to study the locations and types of Nav channels in lungfish, basal ray-fin fishes (e.g., bichirs, gars), a variety of tetrapods, and teleosts to know whether there is parallel ... of different channel “types” in teleosts and tetrapods. For example, fast-firing inhibitory neurons in mammals express different Nav channels than more slowly firing pyramidal neurons. Do we see ...

... diversity in signaling (electric fish), in the arms race against lethal naturally occurring or synthetic toxins (snakes, newts, pufferfish, insects), and in specialized habitats (naked mole rats). There are likely to be more examples of this, especially in animals with unique life histories, and we ...

... I thank Francisco Ayala, John Avise, and Georg Striedter for organizing a stimulating Arthur M. Sackler Colloquium of the National Academy of Sciences and for their invitation to participate....

... Evolution of Centralized Nervous Systems: Two Schools of Evolutionary Thought...

... Understanding the evolution of centralized nervous systems requires an understanding of metazoan phylogenetic interrelationships, their fossil record, the variation in their cephalic neural characters, and the development of these ... . Each of these topics involves comparative approaches, and both cladistic and phenetic methodologies have been applied. Our understanding of metazoan phylogeny has increased greatly with the cladistic analysis of molecular data, and relaxed molecular clocks generally date the origin ... , if not stem clades of bilaterian crown clades. Analysis of brain–body complexity among extant bilaterians indicates that diffuse nerve nets and, possibly, ganglionated cephalic neural systems existed in Ediacaran organisms. An outgroup analysis of cephalic neural characters among extant ... also indicates that the last common bilaterian ancestor possessed a diffuse nerve plexus and that brains evolved independently at least four times. In contrast, the hypothesis of a tripartite brain, based primarily on phenetic analysis of ...

... Laboratory of Comparative Neurobiology, Scripps Institution of Oceanography and Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093. E-mail: rgnorthcutt@ucsd.edu....

... cladistic analysis of the genomes of additional taxa and an increased understanding of character identity genetic networks....

... von Salvini-Plawen and Mayr (1977)...

... Any consideration of the evolution of centralized nervous systems is inextricably linked to an understanding of the phylogeny of living metazoans, their fossil history, the vast range of complexity in their nervous systems, and the development of these ... CNSs must be based on all lines of evidence available. The molecular phylogenetic studies of the last 20 years are particularly important in understanding metazoan interrelationships as well as the time frame in which these animals arose and radiated, and we now have increased insights into the ...

... First, I will review the fossil history of the earliest putative metazoans, and then, I will discuss different comparative approaches to analyzing both molecular and morphological data: the molecular clock hypothesis, which has ... a range of possible dates for the origin and divergence of metazoans; developmental genetics and its contribution to our understanding of the patterning of metazoan bodies, particularly patterning of the CNS; and conclusions based on the first outgroup analysis of metazoan central ...

... The fossil record is notoriously incomplete. Fossils essentially exist as snapshots in time, and these snapshots are of varying quality. Some are grainy, providing only a glimpse of organisms and their ecology; others are fine-grained photographs ... individual taxa and their ecology (Lagerstätten). Regardless, each snapshot provides unique and critical insights into the minimal age of a radiation. Each snapshot helps calibrate molecular clocks, establish ecological settings of evolutionary ... , and reveal unsuspected morphological characters that challenge current conclusions regarding character transformation (Donoghue and Purnell, 2009)....

... The earliest reported fossils of possible metazoan embryos and adults are in the Ediacaran Doushantuo Formation (~570 Mya) in southern China (Xiao et al., 1998; Chen et al., 2000, 2009). Small globular fossils, ~ ... μm in diameter, show remarkable cellular details and have been interpreted as cnidarian gastrulae and planulae as well as bilaterian gastrulae comparable with living molluscans and echinoderms (Chen et al., 2000). However, the interpretation of these ... as bilaterian metazoans has been questioned, and they have been reinterpreted as encysted holozoan protists (Huldtgren et al., 2011). Similar problems plague the earliest reported adult bilaterian, ... Doushantuo Formation of southern China (Chen et al., 2004a,b). Fossils of Vernanimalcula (~200 μm in diameter) have been described as broadly oval and triploblastic with a mouth, a differentiated gut surrounded by paired coeloms, and an anus. The rostral end of these “small spring animals& ... three pairs of external pits that have been interpreted as sensory organs (Chen et al., 2004a). This interpretation has been questioned, however, and these fossils have been claimed to be taphonomic artifacts in which phosphates were deposited within a spherical object, such as the cysts of algal ... (Bengtson and Budd, 2004)....

..., are in the Ediacaran strata above the Doushantuo Formation (Fedonkin et al., 2007). They average 10 cm but reach an extreme of 1 m in length, and they include forms that are frond-, disk-, and worm-like (Fig. 3.1A); their interpretation has had a tumultuous history. Many of these fossils were ... in the late 1940s and were interpreted as representatives of living metazoan phyla. Forms like Eoporpita (Fig. 3.1A, 1) were interpreted as cnidarian pelagic medusa ( ... , 1984), and frond-like forms, such as Charniodiscus (Fig. 3.1A, 2), were interpreted as possible cnidarian sea pins (Glaessner, 1962). Still other forms of these ... were interpreted as stem bilaterians. For example, Dickinsonia (Fig. 3.1A, 3) was interpreted as a flatworm (Glaessner and Wade, 1966), Arkarua (Fig. 3.1A, 4) was interpreted as an echinoderm (Gehling, 1987), Spriggina (Fig. 3.1A, 5) was interpreted as an annelid capable ... active swimming (Birket-Smith, 1981), and Praecambridium (Fig. 3.1A, 6) and a soft-bodied “trilobite” not formally described (Fig. 3.1A, 7) were interpreted as stem arthropods (Glaessner and Wade, 1971; Gehling, ... ). After this burst of descriptions, Ediacaran anatomy was reevaluated; claims were made that all Ediacarans were organized on a quilt-like pattern and represented an independent experiment of nonmetazoan animals, termed the Vendobionta, that failed with the evolution of macrophagous bilaterian ... (Seilacher, 1989; Buss and Seilacher, 1994; McMenamin, 1998). The concept of the Ediacaran biota as Vendobionta...

... FIGURE 3.1 Reconstruction of the Ediacaran (A) and Burgess Shale (B) biotas. The Ediacaran biota is reconstructed to convey maximal morphological complexity. (A) 1, Eoporpita; 2, Charniodiscus; 3, ...

... was generally abandoned, because paleontologists came to realize that the Ediacaran biota represents a wide range of morphological forms (Fedonkin et al., 2007; Erwin et ...

... except Antarctica. These biotas are dispersed among three stratigraphic zones in named assemblages based on a cladistic analysis of their spatial and temporal distribution (Waggoner, 2003): an Avalon assemblage (579 to ~560 Mya), a White Sea assemblage (~560 to ~550 Mya), and a Nama assemblage (~...

... trace fossils, such as surface tracks or shallow horizontal burrows, that would indicate the presence of small bilaterians that had developed muscles and coeloms to hydraulically locomote. One could infer from the Avalon assemblage that small bilaterians had not yet evolved, but this assemblage is the ... deep water; therefore, it is possible that small locomotory bilaterians existed at this time but were restricted to shallow ecological zones (Bottjer and Clapham, 2006)....

... is of particular interest, because it includes Kimberella (Fig. 3.1A, 8), a small, oval-shaped animal that seems to have glided on a muscular foot and have an anterior end that houses a retractable arrow-shaped organ that was used to scratch the upper surface of the microbial mats on which it moved ( ... and Waggoner, 1997; Jensen et al., 2006). Trace fossils in the White Sea assemblage are diverse and suggest the presence of small bilaterians (Erwin et al., 2011)....

... The Nama assemblage has less diversity than either the Avalon or White Sea assemblages, and it is dominated by frond-like taxa, called arboreomorphs, and simple cylindrical, sessile taxa, called erniettomorphs (Waggoner, 2003; Erwin et al., ... ). Bilaterian body fossils are absent, but small calcified shells of Cloudina and Namacalathus and the earliest evidence of predation in the form of holes bored into these calcified shells do occur (Bengtson and Zhao, 1992)....

... Our understanding of body organization and phylogeny of Ediacarans is incomplete, but a conservative interpretation of the paleontological data indicates that most animals existed primarily on ... mats; it was likely a 2D world, with sessile frond-like forms and vagile, small organisms that trophically were suspension feeders and grazers. There is little to no evidence that pelagic medusae existed (Fig. 3.1A, 1),...

... but there is considerable evidence that sponges and sessile cnidarians were scattered across the microbial mats as were a number of bag-, frond-, and spindle-shaped taxa, forming clades that may be unrelated to any living metazoans. One or more of the three radiations of the small vagile organisms ...

..., calcified shells first seen in the late Ediacaran continue to diversify, however, in the early Cambrian to include a wide variety of plates, spines, and small shelly fauna, which seem to be the skeletal elements of bilaterians that ranged from a few millimeters to several centimeters in length ( ... and Missarzhevsky, 1975). Clearly, bilaterians became armored in the Ediacaran–Cambrian transition. This finding suggests that the development of ... mouth parts may have been a key innovation to allow for additional expansion of macrophagous predators, giving rise to the first arms race (Bengtson and Zhao, 1992). The small shelly taxa diversified over the next 14 Myr, which culminated in the Cambrian explosion of bilaterian diversity; this ... well-preserved, soft-bodied Lagerstätten of the Chengjiang biota of the early Cambrian (~525 Mya) from the Yunan Province in South China and the Burgess Shale biota of the Middle Cambrian (~505 Mya) from British Columbia. Each of these biotas has been extensively described (Whittington, ... ; Briggs et al., 1994; Chen et al., 1997; Conway Morris, 1998; Xian-Guang et al., 2004) and analyzed for community composition and structure (Conway Morris, 1986; Zhao et al., 2010)....

... Despite the Chengjiang and Burgess Shale biotas existing in distinctly different environments—the Chengjiang community is thought to have existed in a relatively shallow ... to have existed as a deep-water community on muddy sediments banked against the front of a stromatolite reef (Fig. 3.1B), where it was thus unstable and subject to periodic slumps, carrying parts of the community into deeper, anaerobic waters (Whittington, 1985; Briggs et al., 1994)—both ... share numerous similarities. Both were dominated by arthropods, brachiopods, and priapulid worms (Conway Morris, 1986;...

... Zhao et al., 2010). Approximately 20% of each fauna consisted of sessile or burrowing infaunal species, and each fauna was dominated by epifaunal species, only 4% of which were pelagic. Feeding strategies included suspension feeding and hunting/scavenging, ... complex food chains comparable with those food chains in many modern benthic marine ecosystems (Castro and Huber, 1992). Members of stem and/or crown groups at the bilaterian phylum level are in these Cambrian communities and occupy niches similar to those niches in modern benthic marine ... Shale biota, infaunal species included polychaete annelids such as Burgessochaeta (Fig. 3.1B, 1), brachiopods such as Lingulella (Fig. 3.1B, 2), and priapulid worms such as Ottoia (Fig. 3.1B, 3), which seems to have been an aggressive predator (Briggs et al., 1994). Epifaunal taxa included ... - and detritus-feeding arthropods such as Marrella (Fig. 3.1B, 4), the trilobites Olenoides (Fig. 3.1B, 5) and Naraoia (Fig. 3.1B, 6), and a possible crustacean, Canadaspis (Fig. 3.1B, 7), as well as predatory arthropods such as Sidneyia (Fig. 3.1B, 8), Opabinia (Fig. 3.1B, 9), and ... (Fig. 3.1B, 10), which grew to over 1 m in length and were clearly apex predators. Deuterostomes are also represented in the Cambrian biota of the Burgess Shale: the eocrinoid echinoderm Gogia (Fig. 3.1B, ... 11) and a possible pelagic holothurian, Eldonia (Fig. 3.1B, 12), as well as a possible cephalochordate, Pikaia (Fig. 3.1B, 13)....

... Pikaia-like chordate, Yunnanozoon, which was initially described as a possible cephalochordate with a notochord, segmented trunk muscles, and an expanded pharynx with an endostyle (Chen et al., 1995). This taxon was subsequently reinterpreted as an early vertebrate (Dzik, 1995), and it was then ...

... Early craniates (hagfishes and vertebrates) may also occur in the Chenjiang biota. Haikouella has been interpreted as a craniate-like chordate with a well-developed brain, lateral ... , a pharynx with gills, and a ventral heart (Chen et al., 1999; Mallatt et al., 2003). A subsequent interpretation of the Haikouella material suggests that the head consisted of ... dorsal and ventral movable units connected by external gills (Shu et al., 2003) and that Yunnanozoon and Haikouella are stem group deuterostomes that are allied to vetulicolians, another problematic group in the Chengjiang biota (Shu et al., 2003, 2010). ... , the yunnanozoans (Yunnanozoon, Cathaymyrus, and Haikouella) may be stem cephalochordates,...

... or they may be closely allied to vetulicolians and may possibly be stem deuterostomes....

... The situation is somewhat clearer regarding the first vertebrates from the Chengjiang Lagerstätte. Two genera, Haikouichthys and Myllokunmingia, have been described as agnathan vertebrates, with Haikouichthys said to be closely allied to living lampreys and Myllokunmingia said ... be closely allied to living hagfishes (Shu et al., 1999). However, it has been claimed that this interpretation is based on tenuous characters and that both taxa may form a clade (myllokunmingids) that is basal to living craniates (Janvier, 2003, 2008). Subsequently, another described genus, ... , seems to be a myllokunmingid (Shu, 2003). In any case, these taxa seem to have had paired nasal capsules, large lateral eyes, and, possibly, paired otic capsules, all of which suggest that they may have possessed brains comparable with living agnathan vertebrates (Shu, 2003)....

... Similar taxonomic problems plague a number of the Burgess Shale taxa. Aysheaia (Fig. 3.1B, 14) and Hallucigenia (Fig. 3.1B, 15) have been considered to be primitive onychophoran worms (Briggs et al., 1994) but are more probably an extinct clade ( ... lobopods, which were possibly a stem group of arthropods) (Budd and Telford, 2009). This finding is also true of Opabinia (Fig. 3.1B, 9) and Anomalocaris (Fig. 3.1B, 10), which may be members of a clade of stem arthropods, although their exact relationship to other arthropods is still ... (Budd and Telford, 2009). Odontogriphus (Fig. 3.1B, 16), a pelagic, flattened, 12-cm-long animal with tooth-like elements surrounding the mouth, remains an ... al., 1994). Dinomischus (Fig. 3.1B, 17) poses similar problems. The bodies of these 10-cm-long animals consisted of a calyx, which housed the mouth and anus opening onto the upper surface of the calyx, and a stem, which was anchored in the sediment (Briggs et al., 1994). These animals have been ... with both echinoderms and entoprocts, but their taxonomic affinities are presently unclear. Continued study and the discovery of new fossils will likely resolve their positions....

... Comparative biologists use two very different approaches in formulating evolutionary statements: cladistics (or phylogenetics) (Hennig, 1966; Wiley and Lieberman, 2011) and phenetics (Sokal and Sneath, 1963; Sneath and Sokal, 1973). Both involve comparing traits or characters (any definable attribute ... , following Hennig (1966), divide similar characters among organisms into three categories: shared primitive characters, shared derived characters, and uniquely derived...

... a sequence of branches (a cladogram). In contrast, phenetists say that overall similarities define homologies, which can be recognized by structural and compositional correspondence and are said to be phenetic or operational homologies (Sneath and Sokal, 1973). Phenetists also believe that ...

... these hypotheses can be evaluated objectively by grouping organisms based on shared derived characters. For example, given three taxa—A, B, and C—there are only three possible hypotheses regarding their relatedness: A is more closely related to B; A is more closely related to C; or A, B, ... and C are equally related. Because phylogeny is a historical process that has occurred only one time, only one of these hypotheses can be valid. The ... characters will indicate the valid hypothesis. That is, the genealogical hypothesis that reveals the largest number of shared derived characters and thus requires the fewest independent origins is the one that is supported. (This conclusion was initially based on simple parsimony but has been ... alternate genealogical hypotheses, their “shared derived characters” are revealed to be shared primitive characters or homoplasies (Wiley and Lieberman, 2011). This finding does not mean that such characters are of no phylogenetic interest. Many shared primitive characters are, in fact, ... derived characters at some lower level of the tree of life and thus linked as transformational homologs to shared derived characters at a higher level. In addition, analysis of homoplasious characters can reveal ... and functional constraints in phylogeny. Although transformational homologies do not specifically define taxonomic groups, they become critical in ... ) has given rise to a wide range of evolutionary studies that have attempted to reconstruct the phylogenetic history of molecular characters (Halanych and Passamaneck, 2001), morphological characters (Northcutt, 1984; Butler,...

... 1994; Striedter, 1997), behavioral and ecological characters (Krubitzer et al., 2011), and biogeographical events (Grande and Bemis, 1998). Such studies are usually called cladistic studies, because they rely on the outgroup rule in the work by Hennig (1966), although they ...

... Because of its logic and methodological transparency, cladistics has largely replaced phenetics in zoological systematics, except at the species level, and much of its ... is widely used to analyze the phylogenetic history of both genotypic and phenotypic characters. The phenetic approach is still widely used, however, in developmental genetic studies, in which evolutionary statements are ... until recently, it has been difficult to explore the genetic basis of phenotypic characters widely among different taxa. The roles of both cladistic and phenetic approaches are examined in the next three sections dealing with the molecular clock hypothesis, the genetic basis of bilaterian body plans, ...

... Evolutionary biologists seek to date the origin of metazoan clades and determine the rate at which they evolve. Initially, clade origins were based solely on the earliest occurrence in the fossil record of that clade, ... the temporal rate was established by current rates of sedimentation and, subsequently, radiometric dating (Benton et al., 2009). Given the incompleteness of the fossil record, however, the accuracy of these estimates of ... and tempo were open to question. In the early 1960s, it was discovered that differences between lineages in the number of amino acids in several proteins ... to be roughly linear in time and that evolutionary changes in these proteins, as well as in genes, could be used to infer the separation in time of different lineages (Zuckerkandl ... , 1962; Margoliash, 1963; Kumar, 2005). This discovery led to the neutral theory of molecular evolution, which claimed that most changes in proteins and genes would be neutral and that fixation of these molecules would accumulate at a clock-like rate (Kimura, 1968). It has become clear, however, that ...

... clocks are frequently generated in a two-step process: the most supported cladogram is generated by cladistic analysis of the molecules of interest, and then, a clock is calibrated by using the time of origin of several clades based on the fossil record....

... based on multiple fossil calibration points in regard to the time of origin for metazoan clades. Using mean rates of sequence divergence, the origin and divergence of bilaterians has been placed at ~1.0–1.2 billion years ago (Wray et al., 1996). In contrast, fossil-calibrated molecular clocks ... the origin and divergence of bilaterians at ~700–600 Mya (Bromham et al., 1998; Douzery et al., 2004; Peterson et al., 2004; Peterson and Butterfield, 2005; Erwin et al., 2011). These later dates suggest that, although animals arose during the Cryogenian Period (~850–635 Mya), ... arose and began to radiate during the Ediacaran Period....

... biologists have made spectacular strides in revealing the genetic basis of the regulatory networks that underlie anterior–posterior and dorsoventral patterning of body organization in many bilaterian metazoans (Lewis, 1978; Nüsslein-Volhard and Wieschaus, 1980; Bopp et al., 1986; ... and Jürgens, 1990; McGinnis and Krumlauf, 1992; Holley et al., 1995). Anterior–posterior patterning involves a homeobox gene superfamily in which orthodenticle and its ... (Otx) are expressed in the rostral head, followed more caudally by the expression of paired-box (Pax) genes and most caudally by Hox genes, which continue to be expressed in the trunk. Much early work on body patterning was based on two taxon comparisons ... fruit flies and mice, but this research has now included extensive outgroup analyses (Noll, 1993; Finnerty and Martindale, 1998; Nederbragt et al., 2002; Holland and Takahashi, 2005)....

... of the discovery of the genetic basis of anterior–posterior body patterning in bilaterian metazoans was the realization that Otx, Pax, and Hox genes are also expressed in a rostral to caudal sequence in those bilaterians that possess brains (Reichert and Simeone, 2001; Hirth et al., 2003; ... origin of the brain in bilaterians. The original hypothesis (Hirth et al., 2003) was based on a two-taxon comparison (between an arthropod and chordates), but more recently, this hypothesis...

... three-taxon outgroup analysis (Arendt et al., 2008) involving an annelid (a spiralian protostome), an arthropod (an ecdysozoan protostome), and a mammal (a deuterostome). To date, however, there has been no attempt to polarize expression of these homeobox genes in ecdysozoan or spiralian ... ., 1998; Striedter, 2005). Hopefully, continued study of the genetic regulatory networks underlying anterior–posterior patterning in ecdysozoan and spiralian protostomes will provide additional insights into the phylogeny of these networks and brain evolution in bilaterians....

... of the genetic processes involved in the dorsoventral patterning of the body in several bilaterian metazoans (Holley et al., 1995; De Robertis and Sasai, 1996; Arendt and Nübler-Jung, 1997) may also provide support for the tripartite brain hypothesis. It has been shown that the gene short ... functionally homologous to the gene chordin (chd) in Xenopus; both promote dorsal development, whereas the gene decapentapelgic (dpp) in Drosophila and its homolog bmp-4 in vertebrates promote ventral development (Holley et al., 1995). Both sog and chd, in conjunction with other genes, also promote ... of neurogenic ectoderm. However, the expression of sog and chd are inverted in the blastula of Xenopus relative to their expression in stage 12 embryos of Drosophila. This finding leads to the suggestion that ... evolved from protostomes by a dorsoventral inversion (De Robertis and Sasai, 1996; Arendt and Nübler-Jung, 1997), resurrecting an earlier inversion hypothesis proposed in the work by Geoffroy Saint-Hilaire (1830). If a dorsoventral ... of the body axis occurred with the origin of chordates, then their brains could be considered homologous (De Robertis and Sasai, 1996; Arendt and Nübler-Jung, 1997; Reichert and Simeone, 2001). Once again, this claim is based on a two-taxon phenetic comparison and not a cladistic one. Work ... , reveals the same expression of homeobox genes in the anterior–posterior body axis as in other bilaterians, but the antagonistic actions of sog and dpp do not restrict neural development to the dorsal body surface of this bilaterian (Lowe et al., 2003; Lowe, 2008). This finding suggests that, ... the genetic signaling network is homologous between protostomes and deuterostomes, this network can be deployed to regulate the development of fundamentally different nervous systems. It is possible that the ancestral ... of the regulatory networks involved in anterior–posterior as well as dorsoventral patterning did not extend to patterning CNSs and that elements of these networks were subsequently co-opted in neural development....

... Clearly, it is difficult to discern the connection between genetic networks and phenotypic characters (Conway Morris, 2000a; Wagner, 2007). This discernment will become easier as the phylogeny of particular genetic networks is ... species (Edgecombe et al., 2011), only 8 of these phyla (cnidarians, platyhelminthes, annelids, molluscs, nematodes, arthropods, echinoderms, and chordates) comprise 99% of extant metazoan species, and 4 of these phyla (annelids, some molluscs, arthropods, and chordates) have brains; thus, ...

... regarding a single metazoan cladogram (Adoutte et al., 2000; Glenner et al., 2004; Hejnol et al., 2009; Edgecombe et al., 2011; Erwin et al., 2011) and difficulties in defining distinct central neural characters. Despite these difficulties, comparative molecular studies have clarified much of the ... . All molecular studies recognize bilaterians as a monophyletic taxon divided into two major clades: the protostomes and the deuterostomes (Fig. 3.2). Furthermore, the protostomes can be divided into two superphyla or clades termed the ecdysozoans and the spiralians ( ... ). Conflicts regarding metazoan phylogeny currently center on the contentious relationships of acoelomorph flatworms (Acoela and Nemertodermatida), the genus Xenoturbella (a small ciliated marine worm), and the basal metazoan clades (cnidarians, ctenophores, placozoans, and ... for the present outgroup analysis (with some modifications), because it is the only Bayesian phylogenetic analysis that includes both molecular and morphological data. The Acoela group has been interpreted as the sister group...

... to other deuterostomes (Philippe et al., 2011). The analysis indicates that the last bilaterian common ancestor possessed a diffuse nerve plexus and that brains independently evolved at least four times among bilaterians....

...) or a deuterostome clade, the xenocoelmorphs (Hejnol et al., 2009; Philippe et al., 2011), which includes acoelomorph flatworms, nemertodermatids, and Xenoturbella. When xenacoelmorphs are interpreted as deuterostomes, they are considered either as the sister group to Ambulacraria (Echinodermata and ... ., 2007). The latter interpretation is accepted in the present outgroup analysis. The following characters—or levels of increasing morphological and functional complexity in the cephalic CNSs of extant metazoans—are recognized in the present outgroup analysis: (i) diffuse nerve nets or ...

... nerve plexuses; (ii) simple cerebral ganglia; and (iii) brains, defined as a central collection of neural centers, with distributed and hierarchical functions. A considerable range of morphological complexity occurs within each of these cephalic neural characters (Bullock and Horridge, ... 1965). Diffuse nerve nets range from those nets of cnidarians and ctenophores to those nets in enteropneust hemichordates, in which neural cell bodies occupy a subepidermal nerve plexus with centralized bundles of ... -conducting axons forming dorsal and ventral nerve cords. Cerebral ganglia range from simple, bilobed ganglia in polyclade flatworms to more complex multiple cephalic ganglia in many ... molluscs (Bullock and Horridge, 1965). In most annelids, arthropods, and some cephalopod molluscs, brains form by elaboration of one or more cephalic ganglia, whereas in vertebrates, they form by elaboration of their ... systems in protostomal bilaterians as simple cerebral ganglia or brains is somewhat arbitrary, because the criteria are based on the relative size and functional complexity of the cephalic structure in question. Simple cerebral ganglia and brains in protostome bilaterians thus represent grades of ... morphological and functional complexity. There is a similar problem in defining a “brain” among chordates: cephalochordates possess a brain that is only ... more complex than their spinal cord; they do not seem to have a homolog of the cerebrum in vertebrates; and separation of a thalamus and midbrain does not appear to exist, nor does a cerebellum (Nieuwenhuys et al., 1998; Northcutt, 2003). It is possible that future analyses will reveal ... morphological categories among cephalic neural characteristics in metazoans; if so, this information may help to resolve the definition of a brain and thus contribute to our understanding of the evolution of centralized nervous systems....

... on the cladogram in Fig. 3.2. Polarization of these characters among deuterostomes suggests that a diffuse nerve plexus is the primitive character, and a brain is the derived character. In both ecdysozoan and spiralian clades, simple cerebral ganglia seem to be the primitive character, whereas a ...

... Different conclusions might be reached, however, if xenocoelmorphs were determined not to be deuterostomes (Philippe et al., 2011) but the sister group to all other bilaterians (Adoutte et al., ...

... nerve plexus and brain in deuterostomes. Because the third neural character, simple cerebral ganglion, is the primitive condition in protostome bilaterians, ... examination of the outgroups, xenocoelmorphs and the basal metazoan clades, would still indicate that the last common bilaterian ancestor and the last common metazoan ancestor possessed a diffuse nerve plexus....

... times independently. For example, analysis of cephalic neural characters within the molluscan clade reveals that basal molluscans (monoplacophorians and polyplacophorians) have simple cerebral, pleural, and pedal ganglia interconnected by ventral and lateral medullar cords (Bullock and Horridge, 1965),...

... that the present outgroup analysis may be flawed by mistaking secondary character reductions (degenerative events) for primitive characters (Reichert and Simeone, 2001; Jenner, 2004; Hirth, 2010). If this flaw was the case, 23 of ~30 phyla would have to possess secondarily degenerated cephalic neural ...

...: (i) when the characters are in sessile taxa, (ii) when the characters are in parasitic taxa, (iii) when the characters are in paedomorphic taxa, and (iv) when the characters are in taxa with secondary loss of microRNAs. Three of these criteria have been recognized by zoologists for almost 50 years ... (Bullock and Horridge, 1965). Secondarily simplified characters have long been suspected in sessile tunicate urochordates, bryozoans, phoronids, entoprocts, and ... cestode and trematode flatworms and rhombozoans, which are obligate symbiotes in the nephridia of cephalopod molluscs. Similar secondary simplification also frequently occurs when ... ontogenies are truncated (paedomorphosis), leading to reduction in body size and morphological complexity, which is widely documented in salamanders (Duellman and Trueb, 1986). The fourth criterion, taxa with secondary loss of microRNAs, may offer a molecular explanation for the first three ... , and it may also identify additional taxa characterized by multiple character reductions or losses. Acoela, Platyhelminthes, and Xenoturbella each seem to have secondarily...

... a single system. Furthermore, the fossil record can be of immense value in polarizing life histories when the earliest members of a clade are vagile and shift to a sessile existence or when there are clear trends in body size....

... There are two very different reconstructions of the morphology of the last common bilaterian ancestor (LCBA) or urbilaterian (De Robertis and Sasai, 1996). Many developmental biologists, relying on the roles of numerous genes and gene networks in the development of arthropods and ... LCBA was a morphologically complex organism with anterior–posterior differentiation of a head that possessed paired eyes, a tripartite brain, and a segmented trunk with a differentiated gut, heart, and appendages. In contrast, many paleontologists and zoologists would suggest that the LCBA was ... simpler morphologically, perhaps a small vernanimalcular-like organism that was patterned in both the anterior–posterior and dorsoventral axes but not segmented. This ancestor would have possessed a mouth and anus connecting a differentiated gut surrounded by coelomic ... . The nervous system would have been a diffuse nerve plexus, and the apical pole of the organism would have had simple ocelli composed of both ciliary and rhapdomeric photoreceptors. The trunk may have contained contractile muscle cells but no heart, segmented muscles, or appendages, and locomotion ...

... Both molecular clock and paleontological data indicate that bilaterian metazoans arose ~600–700 Mya during the Ediacaran, and they radiated rapidly into most bilaterian crown clades by the end of the Cambrian (Erwin et al., 2011). It is also clear that most genes involved in ... genetic networks determining anterior–posterior and dorsoventral patterning must already have been in place in the LCBA (Davidson, 2006; Erwin et al., 2011). If the fossils of the Doushantuo ... and some of the macroscopic fossils of the Ediacaran biota, such as Dickinsonia and Kimberella, are interpreted as stem bilaterians, then the body plans of the earliest bilaterians must have been relatively simple and comparable with ... body plans of living placozoans, platyhelminthines, and aplacophoran molluscs. Although neural structures are rarely fossilized, it is possible to relate neural complexity to specific grades of body ... (Bullock and Horridge, 1965). A conservative interpretation of body complexity...

... that these organisms were characterized by diffuse nerve plexuses. A more heterodox interpretation of organisms, such as Spriggina, Praecambridium, and so-called soft-bodied “trilobites,” is that they are members of clades closely related to annelids and arthropods, which would suggest ... may have already evolved cerebral ganglia sufficiently complex to be termed brains. Given the body complexity of Cambrian annelids, arthropods, and chordates, it is reasonable to assume that the CNSs in these clades were characterized by brains. Interestingly, this level of neural complexity may ... have been reached by cephalopod molluscans until the Devonian some 70 Myr later, with the origin of octopod cephalopods (Kluessendorf and Doyle, 2000)....

... Outgroup analysis of inter- and intraclade variations in cephalic neural characters (Fig. 3.2) supports an LCBA model with a diffuse nerve plexus, which subsequently coalesced into ... number of cephalic ganglia and nerve cords or a dorsal hollow neural tube. Hypertrophy and increase in cellular differentiation of cephalic ganglionated and dorsal neural tube systems independently reached levels of neural complexity that ... defined as brains in arthropods, annelids, and some molluscs and chordates....

... Conservation of genetic regulatory networks, which has been termed deep homology (Shubin et al., 2009; Scotland, 2010), has been invoked to claim that all bilaterian brains are homologous (a shared derived character of all bilaterian metazoans) and consist of ... networks determine character identity, whereas others determine character state (Wagner, 2007). Only as the genomes of additional taxa are probed and analyzed cladistically will it be possible to determine if homologous character identity networks underlie phenotypically recognized brain divisions ... all bilaterian metazoans. Meanwhile, metazoan interrelationships and the evolution of their nervous systems will continue to be debated, hopefully, with the reminder by the late renowned invertebrate zoologist, Donald ... . Abbott, to “[c]ultivate a suspicious attitude toward people who do phylogeny” (Brusca and Brusca, 2003)....

... This paper is dedicated to the memory of Theodore H. Bullock, whose encyclopedic knowledge and boundless enthusiasm defined the study of brain evolution for a generation and greatly informed my thinking, and...

... the memory of Sue Commerford, a good friend and superb assistant until her death during the preparation of this manuscript. I thank Jo Griffith for assistance with the illustrations and Mary Sue ... for help with many phases of the research and manuscript preparation. This work was supported by National Science Foundation Grant IBN-0919077 and private funding....