An Increase in Animal Diversity was Facilitated by Ecologically‐Driven Brain Complexity Throughout the Cambrian

ABSTRACT

The Cambrian Explosion is often seen as a singular event requiring an explanation. In fact, it is better represented as a cascade of linked events, each with numerous causes. The iconic middle Cambrian fauna, represented by sites such as the Burgess Shale, is a culmination of several phases of increases in taxonomic diversity and morphological complexity. I focus on an often‐overlooked increase in complexity that took place in a limited number of phyla in parallel after the main “explosion”. This increase in morphological complexity and disparity was facilitated by an increase in the complexity of the central nervous system, which in itself was a selective response to the ecological complexity of the biosphere, which had been increasing from the late Ediacaran. Genetic regulatory components that contributed to an increasingly differentiated and regionalized central nervous system were developmentally co‐opted to increase the differentiation and complexity of additional organ systems. This process took place convergently in arthropods, mollusks, and annelids at different times throughout the Cambrian and, later in the Ordovician, also in vertebrates.

The Brain‐First Hypothesis suggests that the Cambrian transition from animals with simple body plans and simple brains to more complex animals was driven by a selection for brains with increased neural processing, following increased ecological complexity, and the networks underlying brain development were co‐opted to pattern other complex systems.

1. Introduction

The period between the late Ediacaran and the early Cambrian (roughly 550–520 million years ago) is the most dramatic period in the evolution of animal life on Earth [1, 2, 3, 4]. This period represents a sequence of increases in animal complexity and diversity, during which the biosphere transitioned from including a low diversity of mostly sessile suspension or bottom feeders to a world with numerous animal body plans occupying a dynamic tiered ecosystem with diverse feeding modes, comprising a range of motile animals moving using different modes of locomotion in different spaces [5, 6, 7]. This transition is usually referred to as the Cambrian Explosion. However, it is becoming increasingly clear that this term is a misnomer, since it is neither exclusively Cambrian nor a true explosion [8, 9, 10, 11, 12]. The roots of the explosion are in the Ediacaran [13, 14, 15, 16, 17, 18, 19], and the increase in animal diversity continued into the Ordovician [9, 20, 21]

Over the years, there have been many attempts to explain the “cause” of the Cambrian Explosion [8, 15, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32]. These explanations have come from different disciplines and often disagree, because each explanation tries to pinpoint the driving force behind a specific event or process that took place within the period spanning the late Ediacaran and early Cambrian. While most of the attempted explanations are probably correct for the specific event or process they focus on, no one explanation can fully explain the entire transition.

Indeed, the events spanning the border between the Ediacaran and Cambrian are better represented as a cascade. Rather than a single explosive event, we should be thinking about a series of causally linked events or processes. Each of these is dependent on the ones before it and lays the ground for the ones after it. The sequence of events forming what can be called the Cambrian Cascade includes both abiotic changes and biotic changes [4]. In many cases, the abiotic changes are driven by biotic events, and vice versa (e.g., changes in the chemistry and sedimentation of the sea floor were driven by changes in the behavior of animals occupying the sea floor). Many of the events or processes making up the Cambrian Cascade were general to the entire biosphere, and thus were presumably driven by global changes. Some can be seen as “lineage‐internal”, meaning they occurred within a specific lineage of animals (e.g., the evolution of a specific innovation at the origin of a certain clade [33]), whereas others can be seen as “lineage‐interactive”, meaning they were driven by interaction between organisms of different lineages, ultimately affecting both (e.g., predator‐prey evolutionary arms races or competition for resources).

When we look at the distribution of diversity in the animal kingdom, it is clear that it is not distributed evenly. Only a handful of phyla have more than a few thousand species. Furthermore, the phyla that are today the most speciose (Arthropoda, Annelida, Mollusca, and Chordata) are also the ones that display the most complex body plans (manifested by, e.g., segmented and regionalized bodies, complex centralized nervous systems, highly differentiated digestive systems, complex excretory systems, etc.) I will argue that the early stages of the Cambrian Cascade affected almost all lineages within Bilateria, possibly continuing up to the split between the three bilaterian superphyla (Deuterostomia, Ecdysozoa, and Spiralia), whereas later stages affected only specific lineages—those lineages that display higher complexity and higher diversity (See Text 1 for a discussion of defining and identifying complexity). Evolutionary events that drove an increase in complexity in a small number of lineages ultimately led to an increase in taxonomic diversity of those lineages. The late evolution of the complexity of these lineages strongly suggests an independent process in each one, while the similarity in process and outcome suggests a similar or shared driving force, which may have included interactions among different lineages.

Text 1 – Defining and quantifying complexity

Since we are exploring the evolution of complexity, it seems prudent to put down a definition of complexity. This point has been discussed and debated extensively for many years [91, 96, 97, 98, 99], and it is beyond the scope of the current contribution to cover this debate in sufficient detail. Most approaches to quantifying complexity have to do with the number and diversity of constituent parts, be it cell number or the difference between segments in a segmented organism [99]. Within the framework of the current hypothesis, the increase in complexity I am discussing involves an increase in the number and diversity of differentiated organs, in the diversity of serially repeated organs, and in the adaptive specializations of different organs. Under this practical definition, a centipede is more complex than a nematode, and a crayfish is more complex than a centipede. At the level of individual organs, a multicellular metanephridium is more complex than a single‐celled protonephridium. Different organisms can display different levels of complexity and different aspects of complexity in a modular fashion. Nonetheless, organisms with higher degrees of complexity (e.g., arthropods, vertebrates) tend to display complexity in several organ systems and characteristics at once.

Complexity is an inherent characteristic of biological systems in general and of the Earth's biosphere in particular. However, complexity is expensive in terms of genetic and energetic resources, and there is no a priori reason to assume that complexity per se has any inherent evolutionary advantage. There have been many attempts to model the conditions that would lead to an increase in complexity over time [91, 96, 100], and these are often based on emergent phenomena or regulatory complexity, rather than on positive selection for complexity.

There is probably no single metric that can quantify the overall complexity of an entire organism in such a way that one can map it on a phylogenetic tree as though it were a quantitative character. Nonetheless, it is possible to identify lineages that are generally more complex than other lineages, and to identify lineages wherein complexity increases over time, based on some version of the practical definition given above. There are undoubtedly many cases of an increase in complexity over evolutionary time in specific lineages. However, consistent directional increase in complexity is not a universal phenomenon [72]. The Brain‐First Hypothesis aims to explain the directional increase in complexity in three phyla at a crucial stage in the early evolution of the biosphere.

I will briefly review some of the central steps of the cascade, pointing out which were global and which were lineage‐specific or interactive. I will then focus on the step that I suggest led to the convergent increase in complexity and diversity in three of these four lineages, and suggest a novel testable hypothesis for the cause of these increases.

2. The Cambrian Cascade

2.1. Wormworld

When did the Cambrian Cascade begin? As with any continuous event, choosing a starting point is somewhat arbitrary. Since the Cambrian Explosion is usually seen as an explosion in the evolution of Bilateria, I think it is reasonable to place the beginning of the Cascade at the late Ediacaran, in the so‐called Wormworld of the Nama epoch [15]. While the earlier Ediacaran fauna includes within it organisms that are generally accepted to be the ancestors of bilaterians [14, 16, 34, 35, 36, 37, 38], the Wormworld fauna includes the first undisputed prevalence of motile Bilateria.

The Wormworld fauna includes small animals with either light mineral or organic exoskeletons. They appeared about 550 million years ago (Ma), probably in the wake of a mass extinction event [15, 39, 40]. Most of them were probably motile, moving along the sea floor and grazing on the bacterial mat that covered it. The fossil record of this period also includes trace fossils supporting the existence of a plethora of worm‐like animals moving along the ancient sea floor [13, 14, 16, 41, 42].

2.2. Bilaterian Genetic Toolkits and Urbilateria

These early bilaterians likely had a through gut [17, 43]. Indeed, the through‐gut has been suggested to be a specific adaptation to the type of lifestyle that includes moving through a food source [30], as was probably the case for most Wormworld fauna. At the molecular level, it is highly likely that they already had a Hox cluster, with a division into (at least) anterior, central, and posterior class Hox genes [30]. At the regulatory level, they already had distal enhancers, which allow a more complex and fine‐tuned regulation of gene expression [44, 45, 46].

There is an important point (even if seemingly trivial) to be made about this view of the Wormworld fauna. If the crown group of Bilateria already appeared by this point—and there is good reason to believe that it did [16, 17, 47, 48]—any increases in complexity beyond the basic bilaterian body plan must have occurred independently in each separate lineage. Somewhere within the Wormworld fauna was the actual Urbilateria—the common ancestor of all extant bilaterians [49]. Over the years, there has been a debate about how complex Urbilateria actually was [50, 51, 52, 53] (see Text 2 for a review of this debate). There is no reason to assume it was significantly more complex than its contemporaneous worms. It thus follows that all bilaterian characters not found in Wormworld are lineage‐specific autapomorphies.

Text 2–The Urbilateria debate

The debate over the complexity of the hypothetical common ancestor of all Bilateria, dubbed Urbilateria, took place intensively over the late 1990s and early 2000s [49, 50, 52, 53, 101]. The debate has largely died down in recent years, as a complex Urbilateria is inconsistent with the current understanding of early bilaterian evolution. However, references to a complex Urbilateria continue to pop up in the literature [102].

The debate centered around two conflicting models of the last common ancestor of Bilateria. The “complex Urbilateria” model [49, 51] posited an ancestor with a centralized nervous system including an anterior brain, a segmented body plan, a pair of anterior eyes, and a differentiated digestive system with a through‐gut. This model was based on perceived similarities in the developmental genes involved in these structures in different lineages. Similarities include the involvement of Pax‐6 in eye development in numerous species [103], the involvement of the Notch‐Delta pathway and the transcription factor engrailed in segmentation in different lineages, among others [101, 104, 105].

The alternate “simple Urbilateria” model posited an ancestor with no segmentation, minimal cephalization, a simple eye spot, and a gut with a single opening [52, 53]. This model was based on the concept of “deep homology” [106] where shared molecular components could be the result of an ancient role for a given gene in forming a very generalized structure, such as distalless being involved in body outgrowths in general [107], or Pax‐6 being involved in rudimentary light‐sensing cells [103]. Proponents of this view also highlighted the differences in developmental mechanisms between lineages, despite similarities in some of the molecular components [87, 108, 109, 110, 111]. The discovery of Xenacoelomorpha—a group of animals very similar to the predicted simple Urbilateria—as a putative sister group to all other bilaterians provided a realistic model for the bilaterian ancestor [112, 113].

The debate also included a cladistic argument: a single appearance of complex characters is more parsimonious than three independent appearances. On the other hand, numerous losses of complexity were said to be even less likely. Opinions also differed on what should be considered “true” segmentation or a “true” eye.

Ultimately, as our understanding of the early events of bilaterian evolution has become clearer (see main text), it has become increasingly difficult to reconcile a complex Urbilateria with the fossil record. Additional studies on the developmental processes in different lineages, and especially the segmentation process, have highlighted more differences than similarities, further weakening the case for a complex, segmented ancestor. Nonetheless, the degree of similarities between the more complex animal phyla remains an intriguing observation requiring a more plausible explanation than a complex ancestor. The Brain‐First Hypothesis aims to provide such an explanation.

2.3. Three‐Dimensional Ecosystems

The next major step in the cascade occurred at the beginning of the Cambrian. The official base of the Cambrian at 538.8 Ma is defined as the first appearance of trace fossils that penetrate the surface [4]; the first animals that lived in a three‐dimensional world [28]. These fossils are indicative of a change in substrate utilization. Rather than only living on the microbial mat they fed on, animals started burrowing more deeply. This behavior disrupted the microbial mat, ultimately leading to the decline of microbial mats as a significant ecosystem, in what is often termed the “Cambrian substrate revolution” [3, 54, 55, 56]. The disruption of microbial mats led to the extinction of the fauna that relied on it and to the disappearance of the Nama Wormworld [15, 27, 40].

The number and diversity of penetrating trace fossils increased significantly during the first stage of the Cambrian, known as the Fortunian, indicating that changes in behavior were taking place in several different bilaterian lineages [42, 57]. This increasingly complex behavior paved the way for increasingly complex ecological interactions.

2.4. Predation and Tiered Ecosystems

Several other significant events took place at roughly the same time throughout the Fortunian. The sequence and interdependence of these events is not always clear, and they appear to have occurred very rapidly [4]. The fossil record sees an increase in the diversity of small shelly fossils; fragments of exoskeletal structures, defensive spines, claws, feeding organs, and so on [58]. The increased abundance of small shelly fossils is usually interpreted as indicating a rapid evolutionary arms race linked to the appearance of predation and of predator defense mechanisms [59]. There is evidence of some predation in the Nama [28], but it only became widespread and a significant evolutionary factor in the Cambrian [60].

There are very few complete body fossils of the animals of the Fortunian. Nonetheless, we can reasonably speculate that this stage saw an increase in cephalization and in body support structures, including both biomineralized skeletons [29, 61] and coeloms [62]. Stem‐group members of most extant phyla, as well as crown‐group members of several phyla, probably appeared by the end of the Fortunian [7, 62]. These stem and crown‐group members are recognizable by the existence of some or all of the defining synapomorphies of the phyla.

From a molecular regulatory point of view, this stage probably saw an increase in the complexity of chromatin structure and gene regulation [45, 46, 63]. However, most of the molecular machinery responsible for the events of the Fortunian is likely to have appeared in the Nama [8].

2.5. New Body Plans, New Ecologies

The next stages of the early Cambrian are not formally defined and are referred to informally as Stage 2 (Beginning at 530 Ma) and Stage 3 (beginning at 521 Ma). These stages see an increase in the diversity of small shelly fossils [58], followed by an increase in the diversity of body fossils, representing members of numerous different bilaterian lineages [4]. For example, trilobites first appear in the fossil record at the very beginning of Stage 3 [64], indicating that the arthropod body plan had already been assembled by this point. The first putative crown annelid, Dannychaeta tucolus, also dates to this period [65]. Many of the famous sites of exceptional preservation, representing the iconic Cambrian fauna, are from Stage 3 (e.g., Kerygmachela and Halkieria from the Sirius Passet and Leanchoilia and Maotianchaeta from Chengjiang) [66, 67]. The fauna represented in these sites includes representatives of different lineages with varied body plans, occupying benthic, endobenthic, and nektonic habitats. It includes a diversity of predators, suspension feeders, detritivores, herbivores, and more [67], indicating a much more complex and tiered ecosystem than before.

The increase in diversity and ecological complexity that is evident in the fossil record of Cambrian Stage 3 is different from the increases seen in earlier periods. Unlike the first pulses of increase in diversity of the Nama and Fortunian, which were manifested throughout Bilateria, this increase in complexity and diversity only covered a few phyla [68]. This is best demonstrated by the dramatic and rapid increase that occurred in arthropods and their close relatives. Arthropods are completely absent from the body fossil record before the appearance of trilobites 521 Ma [64], although several earlier trace fossils have been interpreted as belonging to arthropods. Trilobites display the full complexity of the arthropod body plan. If their absence from the earlier fossil record is not an artifact, then the arthropod body plan was assembled very rapidly in the few million years before their first appearance in the fossil record [64].

The middle Cambrian, represented by the iconic Burgess Shale fauna [1, 2], among others, sees a turnover in the dominant lineages, but there are no phylum‐level body plans that appear later than the middle Cambrian. There are further increases in diversity, notably in the early Ordovician [20, 21], but the main increases in morphological complexity are by and large complete by this point (but see the vertebrate exception below). Some non‐mineralizing phyla (e.g., nemerteans) as well as some microscopic phyla (such as bryozoans) are absent from the Cambrian fossil record, but it is not clear whether this is a preservation artefact or a true reflection of their late appearance in the fauna.

3. The Brain‐First Hypothesis

An increase in complexity can drive an increase in diversity due to the ability to evolve specialized organs (see Text 1), and thus occupy an increased range of niches through taxon‐specific adaptations of these specialized organs. However, this is not a requirement, and diversity can increase without an increase in morphological complexity. A case in point is the nematodes, which are arguably the most species‐rich phylum (with a very small representation of their diversity described), while maintaining a morphologically simple and conserved body plan [69]. Similarly, priapulans probably reached their peak diversity in the middle Cambrian, but remained relatively simple animals, without strongly differentiated or specialized organs [70]. Another example is the brachiopods, which also increased in diversity over the Cambrian, but despite an increase in species number, did not evolve new or complex organ systems [71].

Conversely, the four phyla in question, Arthropoda, Mollusca, Annelida, and Chordata, show a significant increase in complexity, followed by an increase in diversity. In all four phyla, the increased complexity is manifested by most, if not all, of the following: a complex centralized nervous system composed of a ladder‐like trunk nervous system and an expanded anterior brain, diverse sensory organs with a peripheral nervous system, a complete coelom often with distinct compartments, a circulatory system providing nutrition and oxygen to peripheral tissues, dedicated excretory organs linked to the circulatory system, a differentiated digestive system with a separation between digestion and absorption, and differentiated muscle bundles responsible for different types of movement and locomotion [72, 73]. Not only do these phyla share similarities in complex organ systems, but some of these systems also share some developmental genes. This similarity led some workers to suggest that the complexity stems from a complex common ancestor; the so‐called “complex Urbilateria” hypothesis (Text 2).

The increase in complexity and diversity is most notable in the arthropods, where a complex segmented body plan is evident already in the early stem group [74, 75, 76]. They rapidly became the most diverse animal phylum (at least in terms of known species—see discussion of nematodes above); a status they have held from the Cambrian to the present [75, 77]. Annelids and mollusks attained their complex body plan somewhat later, probably by the mid‐Cambrian, and increased in diversity more slowly. The annelid Cambrian fossil record is extremely sparse, and it is not clear whether this is an outcome of a preservation bias or a true reflection of low diversity. Nonetheless, middle Cambrian annelids display the hallmarks of the typical annelid body plan [65, 78, 79, 80]. The mollusk fossil record is significantly more extensive, mostly due to their mineralized shells. The main lineages within Mollusca must have split during the Cambrian or even earlier, since fossils of shells identified as belonging to individual lineages are found from the early Cambrian and onwards [81], although no body fossils are known from this period. Mollusks then underwent a gradual increase in diversity throughout the Cambrian and Ordovician [81, 82, 83]. The chordates, and specifically the vertebrates, did not increase in complexity or in diversity until the Ordovician [84, 85]. For the sake of the following discussion, we will put the vertebrates aside, since their radiation cannot be disentangled from their hyper‐mineralized skeletons, and we will focus only on the three “invertebrate” phyla.

Despite differences in the dynamics and timing of the evolution of these three phyla, their complexity is manifested in similar ways, such as the appearance of a ladder‐like nervous system with an expanded anterior brain, a regionalized digestive system, and, in two of the three, also segmented body plans [86, 87, 88]. This raises the question of whether a similar selective force drove the increase in complexity in all three, given the similarity in the outcome. If so, it is likely to have been a global selective force that acted on these three phyla convergently, but not on others (or at least, not as strongly). A selective force that works in parallel over time on several different lineages implies a long‐lasting ecosystem‐wide phenomenon. This could be an abiotic factor, or a change in the biological interactions within the ecosystem. I suggest that the main selective force for the convergent increase in complexity was an increase in the need to respond to a more complex environment and process numerous complex environmental inputs. This was a direct outcome of the previous phases of the Cambrian Cascade, wherein the ecosystem became increasingly tiered, and the number of trophic levels and the degree of interspecific interactions increased dramatically [4]. Organisms needed to receive, process, and respond to an increased number of signals coming from different organisms and from different directions.

The outcome of this selective pressure was an improvement of sensory organs and, more importantly, an increase in the size and differentiation of the central nervous system. In order to process diverse sensory inputs, I suggest that there was selection for the central nervous system to become increasingly specialized and regionalized. Processing inputs from different sensory organs was done in different parts of the central nervous system, and especially in the anterior regions of the central nervous system—the brain. Integrating data from different sensory systems required the evolution of additional regionalized sections of the brain, as did the execution of complex behaviors responding to a range of stimuli. The core of the hypothesis I present herein is that the brain was the first organ system to increase in complexity, and I refer to it hereafter as the “Brain‐First Hypothesis” (Figure 1).

FIGURE 1.

Schematic representation of the main points of the Brain First Hypothesis.

The more complex brain was composed of more types of neural cells and was divided into more individualized regions than in the ancestral condition. This regionalized and specialized brain was achieved by an increase in complexity of the developmental program responsible for forming the brain; developing a uniform structure requires much less regulation than developing a differentiated structure. The selection for an increasingly complex brain was manifested as a selection for more tightly regulated and nuanced gene expression patterns. I suggest that this resulted in more complex and combinatorial regulatory regions in the cis‐regulatory modules of relevant genes, increased diversity of splice variants in these genes, more roles for noncoding RNAs, and duplication and sub‐functionalization of both regulatory genes and structural genes involved in neurogenesis. It is these genes and the networks of interactions among them that drive the development of the morphological plan of the brain, and the more complex they are, the more complex the resulting brain will be [46, 89, 90, 91].

While the main driving force for this increased regulatory complexity was the requirement for improved neural processing, it had additional, far‐reaching consequences. I suggest that once these expanded regulatory toolkits and the novel networks emerging from them were in place, they were rapidly and easily co‐opted to regionalize and diversify additional organ systems. Co‐option is a well‐known and described phenomenon in the evolution of novelties [33, 46, 92, 93, 94]. Existing gene regulatory networks are reactivated or reused in novel contexts to give rise to evolutionary novelties. With the increased regulatory complexity, evolution had an “open field” for numerous cases of co‐option. I suggest that these co‐option events allowed additional organ systems to become more highly differentiated, providing the raw material for the increase in general organismic complexity that occurred in the aforementioned three phyla throughout the Cambrian.

A co‐option of neural developmental pathways into other organ systems has already been suggested for the evolution of the arthropod segmentation cascade [87], and indeed for segmentation in general. According to this idea, the similarities in developmental genes between different phyla—previously used as an argument for a complex Urbilateria—result from this convergent co‐option of common neural patterning genes. An increase in sensory functions as a driver of the Cambrian explosion is also an idea that has been suggested in the past [31, 32], but has not gained traction. The Brain‐First Hypothesis suggests that segmentation is only one example of a broader phenomenon and suggests a mechanistic link between the increase in sensory functions and overall complexity.

More highly differentiated and regionalized structures and organs allowed an increase in morphological disparity (the degree to which organisms within a lineage are morphologically different from each other). Taxonomic diversity then increased through a series of adaptive radiations, making use of novelties that appeared as a result of new regulatory elements being recruited to new morphological structures [33]. Thus, the final—but indirect—outcome of the increased ecological complexity of the early Cambrian was an overall increase in taxonomic diversity, with most of this diversity stemming from three phyla with increased complexity.

This process of increasing sensory sensitivity, neural complexity, and morphological diversity probably did not occur at once, but in a gradual, repeated feedback loop over an extended period during the Cambrian, culminating in a significant increase in complexity relative to the ancestral condition. The precise timing and rate of this process varied among phyla, reflecting different dynamics in different lineages. It remains an open question why this process did not occur in other phyla, which were presumably experiencing the same ecological environment. Like many things in evolution, chance events probably had a significant role [1], and our ability to explain why a process didn't occur in a specific lineage is limited. Perhaps the complex phyla already displayed some unknown exaptation to processing complex sensory inputs, or held specific ecological roles, increasing the selective pressure on them to adapt to increasing sensory inputs. This allowed them to adapt and undergo an increase in neural complexity, with accelerating feedback driving the process more rapidly in these lineages. It also remains unknown what drove the early increase in diversity in morphologically less complex taxa (e.g., priapulans or brachiopods).

3.1. Implications and Predictions of the Hypothesis

The hypothesis presented above provides a simple explanation, based on first principles, for the increase in complexity and diversity seen in a limited number of animal lineages after the main diversification of the early Cambrian. Furthermore, this explanation also allows us to formulate a number of predictions and ways to test them, using molecular data from extant organisms. These tests must allow us to differentiate between the Brain‐First Hypothesis and alternative hypotheses. Assuming that general complexity is linked to brain complexity in a limited number of lineages, the alternate hypotheses would be that increased overall complexity evolved earlier (for an unknown reason) and in turn repeatedly drove increased neural complexity (via an unknown mechanism), or that complexity in all organ systems evolved more or less in parallel (under unknown selective pressure). Conversely, an alternate hypothesis would be that complexity is an ancestral character for Bilateria (but see Box 2 for a refutation of this view). In addition, we must also address the possibility that complexity and diversity increased due to random neutral processes and do not require a selective explanation.

First, we would need to test the link between increased morphological complexity and regulatory complexity in the three phyla: Mollusca, Annelida, and Arthropoda. Intuitively, this link seems almost trivial, and molecular evolution is even assumed to be linked to morphological evolution in many models [95], but it has never been empirically studied. We would expect to see the morphological complexity manifested in a higher diversity of a range of regulatory elements. These should include not only regulatory genes such as transcription factors and signaling molecules, but also cis‐regulatory modules, noncoding RNAs, alternative splice variants in structural genes, and more. We should be able to distinguish between increases in regulatory elements that occurred before the diversification of Bilateria and those that occurred only in specific lineages by mapping the diversity of regulatory elements phylogenetically. This will allow us to elucidate which increases in regulatory complexity are shared across large phylogenetic distances and which have independently and convergently evolved in specific lineages. We would expect to see the most significant lineage‐specific increases in regulatory diversity within the three focal phyla. The recent increased availability of high‐quality genomes from representatives of numerous phyla makes this type of analysis an achievable goal. Conversely, if there is no evidence for higher regulatory complexity in mollusks, annelids, and arthropods, this would weaken the link between morphological and regulatory complexity and decrease support for the Brain‐First Hypothesis.

Next, we would need to demonstrate that the increases in regulatory complexity evolved in the nervous system first and that the expanded regulatory toolkit was co‐opted to other morphological structures. Under this assumption, we would expect the largest number and range of regulatory elements to be found in gene regulatory networks involved in the development of the brain in each of the three phyla. If complexity in other organs is a result of co‐option of regulatory elements that originally evolved in the nervous system, only some elements of this neural‐development toolkit should be found in the networks involved in developing other complex organ systems. Furthermore, if this co‐option occurred independently in different organ systems, we would expect different regulatory elements to be found in the development of each system. Finally, this subset of the regulatory toolkit used in different systems would also be different in each phylum. This would indicate that the co‐option of regulatory elements occurred independently not only in each system but also in each lineage. Conversely, if complexity in different organ systems evolved independently of the complexity of the nervous system (either before or after it), we would find system‐specific regulatory elements and would not expect the nervous system to display an unusually large number or range of regulatory elements.

Finally, we would need to demonstrate that lineages that did not increase in complexity during the Cambrian, for example, Priapula, Brachiopoda, Platyhelminthes, and so on, maintain a basic bilaterian regulatory toolkit representing the increase in complexity that occurred in the early phases of the Cambrian Cascade. Studying these lineages from a comparative genomic perspective should provide us with a baseline for what level of regulatory complexity was presumably found in the early Cambrian, before the increase in complexity seen in the three focal phyla. A phylogenetic comparison of the regulatory elements within these lineages should show that they date back to the last common ancestor of Bilateria, or possibly to the last common ancestor of one of the super‐phyla (e.g., Ecdysozoa, Spiralia). We expect a much smaller number of lineage‐specific regulatory innovations compared with the more complex phyla.

Recently, Budd & Mann [95] presented a model that explains differences in clade diversity based on differences in morphological and molecular evolution early in the evolution of the clade. This model is consistent with the Brain‐First Hypothesis, and the pattern it predicts is similar to the pattern presented herein, where specific lineages rapidly undergo linked genetic regulatory and morphological evolution. The Budd & Mann model does not require a selective explanation for these changes and is consistent with a neutral model of evolution. Nonetheless, the Brain‐First Hypothesis provides a possible explanatory mechanism for the Budd & Mann model, at least in the specific case of the Cambrian increase in complexity of mollusks, annelids, and arthropods.

4. Concluding Remarks

Reframing the Cambrian Explosion as a cascade removes the need to find an “explanation” for a singular event. Indeed, each phase in the Cambrian Cascade has its own cause (or several causes). The iconic fauna of the famous fossil sites of the middle Cambrian is not a direct outcome of an increase in animal diversity at the base of the Cambrian, but rather an outcome of several pulses of increased diversity throughout the early and middle Cambrian. This increase in morphological complexity and in disparity in specific lineages was made possible by an increase in the complexity of the central nervous system, which in itself was a selective response to the ecological complexity of the biosphere, which had been increasing from the late Ediacaran. The molecular fingerprints of this process can probably still be found in the most diverse animal groups that exist today. Identifying these fingerprints could help resolve the gaps in the model and clarify why the increase in complexity occurred only in some lineages and not in others.

Author Contributions

Ariel D. Chipman – Conceptualization, analysis, writing.

Conflicts of Interest

None of the authors has a conflicts of interest to disclose

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.