Luwen Zhang- School of Biological Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE, United States
The Cambrian radiation (~539 Ma) generated most animal body plans in ~20 million years. This rapid diversification raises the central question of how genomic innovation for architectural change—rather than merely multicellularity—arose in early animals. We propose that cellular predator–prey interactions among single-celled ancestors, together with motility evolution, drove early genomic change. Failed predation attempts—where prey escaped or predators suffered cellular damage—exposed cells to oxidative and enzymatic stress, triggering error-prone DNA repair and transposable-element activation that produced chromosomal rearrangements including Hox cluster reorganization, regulatory network rewiring, and gene duplications—changes with direct consequences for segmentation, symmetry, and appendage architecture. Motility served as an evolutionary filter: highly motile cells evaded recurrent engulfment, whereas low-motility cells repeatedly experienced predation-induced genomic stress and accumulated heritable variants. Phagocytosis expanded within eukaryotes during the Neoproterozoic, aligning with early animal evolution. The Cambrian “Goldilocks” window—rising oxygen, elevated resources, and low ecological incumbency—both accelerated architectural variant generation and created ecological space for body-plan innovations to persist and elaborate. Our model addresses both multicellularity achievement and subsequent phylum-level architectural diversification, proposing that predation-driven genomic stress generated the substrates later expressed as distinct tissues, axes, and organ systems. This framework accounts for the magnitude, timing, and uniqueness of animal origins while generating testable predictions linking cellular-stress signatures with genomic patterns in early-branching animals.
1 Introduction
The origin and diversification of animals represent a major evolutionary transition comparable to the origin of photosynthesis or the colonization of land. During the Cambrian period (~539 Ma), animals transitioned from cryptic, likely microscopic forms to ecologically dominant, morphologically diverse organisms that restructured marine ecosystems. While paleontological and geochemical evidence indicates that many animal lineages originated earlier in the Ediacaran (635–539 Ma), their ecological expansion and morphological elaboration occurred predominantly in the Cambrian (Carlisle et al., 2024; Wood et al., 2019; Zhang and Shu, 2021).
Understanding this radiation requires explaining both the source of evolutionary novelty and the context that permitted its expression. Recent work has identified several permissive environmental conditions: modest increases in ocean oxygenation may have enabled larger, more active organisms; nutrient availability supported higher productivity; and evolving developmental gene networks potentially provided the regulatory flexibility for body plan diversity (Alexander et al., 2025; Carroll, 2008; Marshall, 2006; Shubin et al., 2009; Stockey et al., 2024). However, these accounts describe the conditions for diversification without specifying a mechanism for generating the concentrated genomic variation upon which selection could act.
This paper advances an ecological and mechanistic hypothesis: repeated predator–prey interactions and the evolution of motility jointly acted as the engines of early genomic innovation. In this framework, failed eukaryote–eukaryote predation (incomplete phagocytosis) generated bursts of DNA damage and error-prone repair, producing heritable genomic variation far above background mutation rates. Motility then became the evolutionary filter determining lineage fate—organisms that retained high motility persisted as unicellular choanoflagellate-like forms, whereas those that lost motility were driven toward obligate multicellularity. Together, these processes supplied both the raw material and the selective asymmetry necessary for the Cambrian explosion.
While multicellularity emerged long before the Cambrian, the key evolutionary challenge was the origin of body-plan–level disparity—the differentiated architectures characteristic of metazoan phyla. Accordingly, this model is not intended to explain the origin of multicellularity per se, but rather the generation of the genomic substrate for architectural innovation, including adhesion modules, regulatory networks, and developmental patterning systems. These features, produced through repeated predation-induced genomic stress, set the stage for the rapid elaboration of tissues, axes, and organ systems during the Cambrian.
Unlike gradualist models emphasizing steady genetic drift, the predation–motility hypothesis, envisions an episodic engine of innovation: predation created genomic instability, and motility shaped which variants survived or transitioned to multicellular organization. This mechanism helps explain why metazoan diversification was so rapid and why it produced such a remarkable array of forms in a geologically brief interval.
The hypothesis yields testable predictions: cells surviving failed predation should exhibit genomic signatures of stress-induced repair and transposable element activation, and comparative genomics should reveal concentrated chromosomal rearrangements near adhesion and developmental genes in early animal lineages. By linking cellular predation, motility evolution, and genomic innovation, this model provides a mechanistic foundation for the emergence of animal body-plan complexity, not merely multicellularity.
2 The cellular predation–motility hypothesis
2.1 Cellular predation and the evolution of motility
In Proterozoic oceans, unicellular ancestors of animals (holozoans) engaged in predator–prey interactions through phagocytosis—engulfing and digesting other eukaryotic cells. These encounters were not always lethal: prey sometimes escaped or damaged their predators, leaving behind cellular survivors bearing stress-induced genomic changes. We define “failed predation” as a predator–prey encounter in which engulfment occurs but digestion remains incomplete, allowing one or both participants to survive with varying degrees of cellular damage.
Unlike successful predation, which merely transfers energy, or failed capture, which leaves no lasting consequence, failed predation creates a unique selective scenario: survivors endure severe but non-lethal stress that may lead to heritable genomic alterations (Figure 1). This concept differs from the classical “frustrated phagocytosis,” a pathological process in modern immune systems where phagocytes encounter indigestible particles, leading to inflammation or cell death (Francis et al., 2022; Kzhyshkowska et al., 2015). In contrast, failed predation in our framework describes normal ecological interactions among unicellular eukaryotes, where incomplete digestion yields viable survivors carrying transmissible genomic changes rather than cellular dysfunction.
Figure 1. Cellular Predation-Induced Genomic Instability. Mechanistic routes from incomplete phagocytosis to genomic novelty via three non-exclusive routes. (A) Prey escape. Prey escapes the phagolysosome (acidified phagosome–lysosome), experiencing DNA damage from acid, hydrolases, and reactive oxygen species (ROS); error-prone repair (non-homologous end joining, NHEJ; alt-EJ/HR) can yield structural variants (SV). (B) Predator disruption. Prey damages the phagosomal membrane, allowing lysosomal contents/ROS to leak into predator cytoplasm; ensuing DNA damage may be resolved by error-prone repair, producing SVs. (C) Transient chimerism/DNA exchange. Bidirectional membrane rupture can briefly mix cellular contents, permitting rare chimerism or DNA transfer. TE activation via stress-induced depression is not shown. Colored bars denote chromosomes; blue circles denote phagosomes/lysosomes. (D) Evolutionary trajectories. Post-predation cells face selection for metabolic autonomy and reproductive capacity. (Upper) Metabolism+/Reproduction+: Complete survivors retain both functions and can evolve toward multicellularity after genomic stabilization. Critically, these viable cells re-enter the ecosystem, becoming subject to further cycles of predation. Each cycle represents another opportunity for genomic alteration and refinement, cumulatively building genetic complexity. This iterative process, followed by genomic stabilization, can ultimately lead to multicellularity. (Lower) Metabolism-/Reproduction+: Metabolically compromised cells become obligate parasites while retaining reproductive ability.
Such encounters likely produced an evolutionary feedback loop between phagocytosis and motility. Cells with higher motility could more effectively evade engulfment, while slower cells endured repeated predation stress, accumulating heritable genomic rearrangements that occasionally conferred new traits. Over evolutionary time, motility both shaped and was shaped by predation pressure—linking ecological behavior and genomic innovation within a single, self-reinforcing process. This framework extends traditional models of phagocytic interaction by embedding them within an ecological arms race, where motility emerged as the critical survival trait and a primary driver of evolutionary divergence.
2.2 From cellular stress to heritable variation
Failed predation exposed both predator and prey to oxidative, enzymatic, and mechanical stress. Surviving cells activated repair pathways under extreme conditions—acidic pH, high reactive oxygen species, metal-catalyzed damage, and membrane rupture—that overwhelmed high-fidelity repair and triggered error-prone repair mechanisms such as non-homologous end joining (Anbar et al., 2007; Hanscom and McVey, 2020; Ratnaparkhe et al., 2018; Rodgers and McVey, 2016; Zhu et al., 2021). These stress-induced repairs produced bursts of chromosomal rearrangements, transposable element activation, and gene fusions—episodic genomic crises that accelerated variation generation. Unlike random mutation, these crises were ecologically triggered by failed predation, making variation frequency a function of encounter rate and motility.
The environmental backdrop likely intensified these effects. Mutation rates estimated from modern laboratory conditions (21% O2, stable temperature) probably underestimate the potential for damage in ancient seas. Ediacaran–Cambrian oceans were relatively hypoxic (~2–10% PAL O2), a condition that slows DNA-repair kinetics, while fluctuating temperatures and metal-rich waters promoted additional oxidative stress (Reinhard et al., 2016; Sperling et al., 2013). Under such conditions, the combined assault of acidification, oxidative radicals, and membrane rupture would have repeatedly overwhelmed high-fidelity repair, favoring rapid but inaccurate pathways that generated structural variants in bursts.
Importantly, even under normal circumstances, homologous recombination and replication stress can generate structural variation (Currall et al., 2013), but the cellular environment of failed predation created a far more extreme context. By concentrating multiple types of DNA damage within a narrow temporal window, it localized genomic instability without requiring globally deficient repair systems. In this way, failed predation acted as a naturally recurring, high-intensity generator of heritable genomic innovation—a cellular crucible where environmental stress, ecological interaction, and evolutionary potential converged.
2.3 Routes to genetic novelty
Failed predation generated genetic variation through three complementary routes (Figure 1):
(A) Prey escape with damage—prey partially digested or oxidatively stressed during attempted engulfment underwent error-prone repair, yielding rearranged genomes (Blackford and Jackson, 2017; Chang et al., 2017; Ciccia and Elledge, 2010; Hakem, 2008; Lieber, 2010); (B) Predator disruption—prey damaged predator membranes, leaking lysosomal contents that mutagenized the predator’s genome (Pauwels et al., 2017); and (C) Transient cellular mixing—partial membrane fusion created temporary chimeras permitting DNA exchange and transposable element activation (Galhardo et al., 2007; Lanciano and Mirouze, 2018; McClintock, 1984; Slotkin and Martienssen, 2007; Soucy et al., 2015). Each pathway amplified heritable genomic diversity under ecological selection. Critically, the likelihood of each event scaled inversely with motility: highly motile cells avoided encounters, while low-motility cells endured repeated genomic reshuffling. The recurrent nature of these interactions transformed phagocytosis from a feeding mode into a genomic innovation engine.
2.4 Evolutionary trajectories and selective filters
After each failed predation event, survivor cells faced multiple selective filters centered on metabolic autonomy and replicative competence. Only those retaining both capabilities—”complete survivors”—could recover and re-enter ecological cycles (Figure 1). These cells had to stabilize damaged genomes, restore energy balance, and maintain sufficient biosynthetic capacity to reproduce (Caetano-Anollés et al., 2009; Eigen, 1971; Fani, 2012; Szathmáry and Smith, 1995).
Motility added a third, decisive filter. Fast-moving cells could escape engulfment, while slower cells were repeatedly exposed to predation stress and accumulated heritable mutations. Under these conditions, variants that enhanced adhesion and cooperation gained a selective advantage, favoring survival through aggregation rather than individual escape. Facultative colonies in choanoflagellates such as Salpingoeca rosetta show that adhesion toolkits predate animals, but these colonies remain transient because individual cells retain motility (Dayel et al., 2011; Fairclough et al., 2010).
In contrast, animal multicellularity is obligate and differentiated, marked by stable adhesion, division of labor, and loss of independent motility in most somatic cells. We suggest that this transformation reflects distinct selective environments: retentively motile lineages experienced only intermittent pressure to aggregate (Track 2, Figure 2), whereas motility-lost lineages faced continuous predation without escape, selecting for irreversible adhesion and tissue-level organization (Track 1, Figure 2). Multicellularity has arisen many times across eukaryotes, but what distinguishes animals is the evolution of persistent, integrated multicellularity that became advantageous only when individual motility was no longer viable.
Figure 2. Motility-driven divergence and the origin of animal body plans. (A) Geological framework. Timeline from the Tonian (~1000 Ma) to the early Cambrian (539–520 Ma) showing key evolutionary transitions and the temporal context of animal origins (ICS Chart v. 2024/12; not to scale). (B) Evolutionary trajectories from a unicellular ancestor to animals. Cell X variants (survivors of failed phagocytosis) produced a unicellular grade holozoan precursor (UHP, ~1000 Ma) with high motility and complete adhesion/stemness toolkits. By ~900 Ma, motility-driven divergence generated two lineages: Track 1 (upper, red-to-green)—low-motility forms that evolved multicellularity through regulatory rewiring of ancestral toolkits. Through cryptic evolution (~900–635 Ma), these lineages developed simple cell aggregates, progressing to morphologically distinct Ediacaran prototypes with quilted, tubicolous, and frondose body plans (~635–539 Ma). The Cambrian “Goldilocks moment” (~539–520 Ma) —rising oxygen, productivity, and ecological opportunity—amplified existing genomic variation, driving explosive diversification of crown-group animals. Track 2 (lower, gray)—high-motility forms that remained morphologically conserved (choanoflagellate-like, ~900 Ma–present). Solid color balls=UHP variants; Red wedges = selective filters; circles = predation-selection cycles; red lines = genomic evolution; blue lines = organismal trajectories (thickness = complexity); black tails=high motility. (C) Mechanistic summary. The UHP underwent failed phagocytosis (~900 Ma), generating divergent outcomes: Track 1 (upper): loss of motility created ecological crises that selected for obligate deployment of adhesion and stemness networks, producing multicellular tissues, muscle-based movement, and morphological disparity. Track 2 (lower): retention of motility removed pressure for such rewiring, preserving unicellularity and morphological simplicity.
This selection regime—genomic stabilization through survival and functional adaptation through motility loss—might structure early holozoan evolution, driving a deep bifurcation between motile unicellular persistence and sessile multicellular innovation. The balance between these selective pressures prefigured the evolutionary divide separating modern choanoflagellates and metazoans (Figure 2).
An additional trajectory led to parasitism (Figure 1). Some survivors failed to maintain metabolic autonomy but retained replicative capacity, evolving toward parasitic lifestyles dependent on host cells for nutrients and protection. These metabolic-negative, replicative-positive lineages represent an alternative outcome of failed predation, demonstrating how the same cellular encounter could yield divergent evolutionary paths depending on which functions endured (Figure 1). In this broader framework, failed predation acted not as a singular event but as a recurrent selective crucible—sorting cells into distinct fates of autonomy, cooperation, or dependency, each shaping the early diversity of eukaryotic life.
2.5 From altered cells to complex animals
Predation-induced genomic instability supplied abundant raw material for selection, but the rise of animal multicellularity required a distinctive evolutionary route. We propose that a single lineage—the Unicellular-grade Holozoan Precursor (UHP)—served as the key intermediary linking failed phagocytic predation to the emergence of complex metazoan-grade multicellularity.
Among the heterogeneous survivors of failed predation, the UHP combined three traits rarely united in other holozoans: metabolic autonomy, replicative robustness, and high cell-level motility. These properties allowed persistent exposure to predation pressures while maintaining ecological independence. Under such conditions, repeated episodes of predation-induced stress produced cumulative genomic innovation, particularly in adhesion, polarity, and stemness toolkits—gene families repeatedly implicated in early animal multicellularity.
Importantly, this model distinguishes between the widespread, facultative multicellularity seen in extant choanoflagellates and the obligate, developmentally integrated multicellularity characteristic of animals. Like Salpingoeca rosetta, the UHP likely possessed a pre-existing ability to form temporary colonies; however, in lineages that became “unlucky” through loss of motility, escape from predators was no longer possible. In such sessile descendants, recurring failed predation acted as a potent molecular engine: stress-induced, error-prone repair promoted gene duplications, domain shuffling, and regulatory rewiring in adhesion modules. These changes favored stable, cohesive aggregates capable of damage repair, metabolic complementarity, and coordinated cell-cycle control—key transitions toward obligate multicellularity (Cohn, 2010; Hynes and Zhao, 2000; Nit et al., 2021; Zhang et al., 2021). Thus, animal multicellularity is hypothesized to arise not from de novo genetic invention but from reorganization and expansion of the UHP’s ancestral toolkit under persistent predation stress. The resulting mosaic genomic architecture may have predated the Cambrian and ultimately enabled the emergence of tissues, axes, and organ systems in crown-group animals (Figure 2).
2.6 The predation–motility synthesis
We synthesize the preceding sections into the Predation–Motility Hypothesis, in which repeated cycles of failed predation generated bursts of genomic novelty, and motility determined which lineages experienced those events. The UHP represents the pivotal lineage in this feedback system. High-motility variants escaped frequent predation and remained largely unicellular, evolving into morphologically conserved choanoflagellate-like forms. Low-motility variants, by contrast, were repeatedly subjected to predation-induced stress, accumulating structural and regulatory innovations that enabled stable multicellular organization.
Comparative genomics supports this division: modern choanoflagellates exhibit high motility and conserved genomic architecture, whereas early metazoans show extensive chromosomal rearrangements, expanded adhesion and signaling gene families, and regulatory innovation. These differences trace back to contrasting evolutionary experiences within the same ancestral UHP framework. But sessile existence alone is not sufficient; it requires the genomic changes and ecological pressures proposed by the model. We emphasize that these predation–motility cycles achieved two things. First, they accumulated clustered structural variants near genes that later became essential for animal body-plan patterning. Second, they also generated latent developmental potential. This potential could subsequently be co-opted during the Ediacaran and rapidly elaborated during the Cambrian.
3 Supporting evidence
3.1 Endosymbiosis as empirical evidence for heritable gene transfer via phagocytic engulfment
Mitochondrial endosymbiosis provides the most compelling empirical demonstration that phagocytosis can generate heritable, genome-wide innovation. Approximately 1.8–2.0 billion years ago, an α-proteobacterial ancestor was engulfed by a proto-eukaryotic host but escaped complete digestion, initiating extensive and heritable genomic restructuring within the host nucleus. More than 90% of the bacterial genome was transferred to the host nucleus through endosymbiotic gene transfer (EGT), while hundreds of bacterial-derived genes were integrated into novel eukaryotic biochemical and regulatory pathways (Gray, 2012; Martin et al., 2015; Timmis et al., 2004). Concurrently, mitochondrial DNA underwent rapid mutational change, deletion, and rearrangement, with ancestral gene orders still detectable in jakobids (Gray, 2012; Lang et al., 1997). This merger produced chimeric systems for transcription, splicing, and cell-cycle regulations that define modern eukaryotes (Koonin, 2015; Zaremba-Niedzwiedzka et al., 2017). These observations show that incomplete engulfment can trigger large-scale, heritable genomic transformation—the same class of cellular event proposed here for early holozoans during repeated failed predation.
3.2 Comparative genomics reveals evolutionary signatures
Genomic analyses of early-branching animals—including sponges, ctenophores, and placozoans—reveal concentrated episodes of genomic reorganization marked by synteny breaks, chromosomal rearrangements, horizontal-gene-transfer candidates, and expansions of gene families for adhesion, signaling, and development. These patterns parallel expectations from the Predation–Motility Hypothesis: ancient holozoan cells engaged in phagocytic interactions that sometimes failed, exposing genomes to oxidative and enzymatic stress that promoted error-prone repair. These genomic changes are strategically concentrated within the developmental and stemness toolkit, featuring expansions of adhesion and signaling gene families that enabled new tissue organizations and body axes, coupled with regulatory rearrangements near key transcription factors that facilitated the evolution of novel gene regulatory networks for specialized cell types and structures (Sebé-Pedrós et al., 2017; Simakov et al., 2020). The resulting rearrangements might become heritable innovations, providing the raw material later amplified in the Cambrian. Collectively, these molecular signatures may represent “genomic fossils” of predation-driven stress and repair cycles—echoes of ancient ecological encounters that both relied on and re-shaped cellular communication networks (Erwin et al., 2011; Gladyshev et al., 2008; Simakov et al., 2013; Srivastava et al., 2010).
3.3 Ancient cellular capabilities make the hypothesis plausible
The cellular mechanisms central to our model—phagocytosis, DNA-damage repair, and membrane dynamics—are ancient eukaryotic features that long predate animal origins (Mills, 2020; Prorok et al., 2021; Zachar and Boza, 2020). Phylogenetic analyses indicate that phagocytosis arose or expanded multiple times during the Neoproterozoic, coinciding with holozoan diversification (Mills, 2020). When eukaryote-eukaryote engulfment failed, both predator and prey experienced acute oxidative and enzymatic stress, activating repair pathways—homologous recombination and non-homologous end joining—that could generate large-scale rearrangements (Chang et al., 2017; Dupré-Crochet et al., 2013; Hakem, 2008; Lieber, 2010; Yang et al., 2018). The outcome—clustered structural variants and novel gene fusions—is precisely what the hypothesis predicts. Thus, the molecular toolkit required for phagocytosis-induced genome remodeling was already present in the UHP lineage, awaiting ecological activation through recurrent failed predation.
3.4 Stress-responsive transposable elements as a parallel mechanism
Transposable elements (TEs) provide an additional, independently supported route by which stress during failed predation could produce heritable genomic change. TEs are ancient, widespread, and stress-responsive across eukaryotes (Gladyshev et al., 2008; Lanciano and Mirouze, 2018; Slotkin and Martienssen, 2007). Laboratory studies show that oxidative and DNA-damage stress can derepress TE silencing, generating transcriptional bursts and new insertions that restructure nearby chromosomal regions (Galhardo et al., 2007; McClintock, 1984). Because the enzymatic machinery for TE mobilization—reverse transcriptases, integrases, and small-RNA suppression pathways—was already present in the UHP’s ancestral genome, predation-induced crises could readily activate these elements. Each failed-predation event thus coupled physical DNA exchange with TE-driven insertional bursts, producing the clustered rearrangements observed in early metazoan genomes (Kapitonov and Jurka, 2008; Pritham, 2009; Rebollo et al., 2012; Slotkin and Martienssen, 2007).
3.5 Modern predator–prey systems demonstrate rapid evolutionary response
Modern ecosystems provide mechanistic analogs for how predation drives accelerated evolution. Although direct evidence of heritable genomic change from failed eukaryote–eukaryote phagocytosis is lacking, analogous processes occur in microbial predators. The bacterium Bdellovibrio bacteriovorus and predatory myxobacteria exhibit extensive horizontal gene transfer and accessory-genome expansion linked to predatory lifestyles (Hobley et al., 2012; Phillips et al., 2022). Eukaryotic phagocytes also display oxidative DNA damage during feeding, while some prey—such as fungi—can survive engulfment via non-lytic exocytosis, occasionally exporting intact genetic material (García-Rodas et al., 2011; Kalafati et al., 2022; May et al., 2016; Zauberman et al., 2008). Predator–prey co-culture experiments further show rapid phenotypic and genomic shifts under predation stress (Matz and Kjelleberg, 2005). These examples confirm that predator–prey interactions can act as evolutionary accelerators, creating heritable variation above background mutation rates and illustrating the ecological plausibility of predation-induced genomic instability.
3.6 Process-level analogies: cancer, parasitism, and survival outcomes
Two modern biological processes illuminate how cellular stress can generate heritable variation:
(1) Chromosomal instability in cancer shows that overwhelmed repair systems can produce catastrophic rearrangements and rapid adaptive diversification (Cesare and Reddel, 2010; Hanahan and Weinberg, 2011; Maciejowski and de Lange, 2017; Pickett and Reddel, 2015). Similarly, failed predation imposes concentrated oxidative and mechanical stress that biases repair toward error-prone pathways, creating clustered variants—a somatic-level analog of our mechanism. (2) Intracellular parasitism exemplifies alternative evolutionary outcomes of failed cellular engulfment. Many modern parasites persist within host digestive compartments, having evolved mechanisms to tolerate or evade phagolysosomal stress. These lineages typically lose metabolic autonomy while retaining replicative capacity—corresponding to the “metabolic–negative, replicative–positive” trajectory predicted by our model (Figure 1). Examples include Leishmania within macrophages (Carneiro and Peters, 2021; Hsiao et al., 2011; Huynh et al., 2006); phagocytosis-adapted biotrophs such as Phytomyxea and giant viruses that exploit host phagocytic machinery for entry and gene exchange (Aquino et al., 2024; Garvetto et al., 2023).
Collectively, these analogs reveal a continuum of outcomes arising from cellular crises: from cooperative multicellularity to parasitism. Though occurring in modern contexts, they affirm the plausibility that ancient phagocytic encounters could have produced viable, genetically divergent lineages—survivors that mobilized DNA, adapted to stress, and explored new evolutionary spaces much like those that eventually gave rise to animals.
3.7 Alternative evolutionary pathways in algae
Algae offer an instructive comparison. Although they occupied the same Neoproterozoic oceans as holozoans, most algal lineages were photosynthetic with rigid cell walls that prevented phagotrophic among themselves (Domozych et al., 2012; Leliaert et al., 2012). Lacking predator–prey interactions, they experienced lower oxidative stress and thus evolved primarily through gene and whole-genome duplications rather than recurrent chromosomal rearrangements (Qiao et al., 2019). This ecological contrast underscores a key prediction of the Predation–Motility Hypothesis: lineages shielded from phagocytic stress followed slower routes to complexity, while phagotrophic holozoans—subject to failed predation—underwent accelerated genomic innovation. Some mixotrophic algae, capable of both photosynthesis and phagotrophy, represent intermediate cases (Flynn et al., 2013).
3.8 Evidence supporting motility reduction as a developmental turning point
3.8.1 Genomic evidence for an ancestral motile state
Comparative genomics indicates that the last unicellular relatives of animals possessed high cell-level motility and a complete adhesion and stemness toolkit, including cadherins, integrins, and key regulatory modules (Sox-like, Myc-like, Notch/Wnt/TGF-β) (King et al., 2008; Richter and King, 2013). The ability of species such as Salpingoeca rosetta to form facultative colonies shows that multicellularity-capable adhesion machinery predates animals and the UHP was likely facultatively multicellular (Fairclough et al., 2010).
These features are consistent with a UHP that possessed metabolic autonomy, replicative robustness, and strong motility—the three ecological filters outlined in Figure 2. In this framework, the loss of motility, rather than new gene invention, served as the principal transition enabling adhesion-based multicellularity (Erwin and Valentine, 2013; Fritz-Laylin, 2020; Hammarlund et al., 2018). Molecular-clock estimates place this shift near the animal–choanoflagellate split (~900 Ma), supporting the inference that motility reduction preceded early multicellular organization (Cavalier-Smith, 2017; Erwin et al., 2011; Parfrey et al., 2011; Sebé-Pedrós et al., 2017)(Figure 2).
Flagellar hyper-motility was not a late (~900 Ma) innovation restricted to choanoflagellates but an ancestral opisthokont condition inherited by the UHP (Steenkamp et al., 2006; Torruella et al., 2015). The resulting paradox—that Earth’s most motile animals arose from low-motility ancestors—illustrates how evolutionary constraint can drive innovation, forcing tissue-level solutions to cellular limitations (Erwin and Valentine, 2013; Fritz-Laylin, 2020; Hammarlund et al., 2018; King et al., 2008; Szathmáry and Smith, 1995).
3.8.2 Paleontological and experimental consistency
It is obvious that the fossil record cannot directly document cellular motility states in unicellular ancestors. However, macroscopic patterns are consistent with the predicted outcomes of motility loss. Increasing trace-fossil complexity from simple horizontal trails (~560 Ma) to three-dimensional burrows in the early Cambrian reflects the later rise of muscle-based locomotion in bilaterians (Budd and Jensen, 2017; Erwin and Valentine, 2013; Jensen et al., 2005; Mángano and Buatois, 2014).
Ediacaran macrofossils, by contrast, predominantly exhibit sessile or modular architectures, aligning with expectations for low-motility multicellular forms preceding active movement (Matz and Kjelleberg, 2005). Comparative ecology further supports this principle, as mixotrophic protists exhibit adaptive shifts between motile and sessile behaviors under predation stress, echoing early holozoan dynamics (Flynn et al., 2013).
3.8.3 Indicators of motility loss in the animal stem lineage
Multiple independent observations support the idea that early animals arose from motility-reduced ancestors. A) Phylogenetic bracketing: Choanoflagellates are highly motile, whereas most animal somatic cells are non-flagellated, implying motility reduction along the stem lineage (King et al., 2008). B) Sponge choanocytes: These flagellated cells are embedded within a sessile body plan, consistent with formerly free-living motile cells becoming integrated into multicellular tissues (Brunet and King, 2017; Richter and King, 2013). C) Ediacaran body plans: Early macroscopic animals are overwhelmingly sessile or mat-attached, indicating that active locomotion evolved only later, near the Ediacaran–Cambrian boundary (Droser and Gehling, 2015). D) Within-lineage precedents: Sessile Acanthoecida demonstrate that motility loss is a recurrent trajectory even within choanoflagellates (Leadbeater, 2015). Likewise, the single posterior flagellum—ancestral to opisthokonts—was independently lost in most fungal lineages (Liu et al., 2006)., indicating that motility reduction in UHP variants has clear evolutionary precedent.
Collectively, these lines of evidence support the hypothesis that progressive loss of cellular motility played a central role in the transition from motile unicellular ancestors to adhesion-based multicellular animals.
4 The Cambrian period: an ecological window for evolutionary innovation
4.1 Why the Cambrian? Ecological opportunity and evolutionary amplification
The Cambrian radiation represents a polythetic evolutionary transition—one requiring multiple necessary but individually insufficient conditions to converge simultaneously. It reflects not only the sudden origin of novelty but also an ecological window that favored the retention and elaboration of variants accumulated during earlier cryptic evolution. It was a “Goldilocks” (enabling–amplifying) context created by a unique convergence of permissive conditions that boosted diversification within animal precursors rather than a single external trigger. This window amplified the effects of the repeated predation–selection cycles that had been operating throughout the Ediacaran. Critically, the Cambrian radiation occurred well above the phylogenetic node of multicellularity—which had been achieved hundreds of millions of years earlier in the Ediacaran (~900–635 Ma). The diversification is not about organisms becoming multicellular, but about multicellular lineages rapidly elaborating distinct architectural solutions: segmented versus non-segmented body plans, bilateral versus radial symmetry, jointed appendages versus parapodia, exoskeletons versus endoskeletons. These phylum-defining architectural features represent the outcome of Hox cluster rearrangements (referring to the Homeobox genes that control the body axis and segment identity in animals), regulatory network rewiring, and gene family expansion specific genomic changes with direct developmental consequences. The cellular predation-motility hypothesis addresses how cellular-level genomic stress generated these architectural variants throughout the Ediacaran, and why the Cambrian provided uniquely favorable conditions for their ecological elaboration and stabilization.
Three factors converged: First, preexisting genetic variation from Ediacaran cryptic evolution. Molecular clocks indicate that many animal lineages diverged in the Ediacaran yet remained ecologically cryptic and morphologically simple. Genomically altered UHP variants provided the biological substrate for later elaboration (Cunningham et al., 2017; dos Reis et al., 2015). These lineages already carried adhesion and stemness toolkits generated by predation-induced genomic reshuffling, ready to be redeployed once ecological opportunity arose.
Second, Resource Abundance and Physiological Capacity (The Intensity Amplifier): This factor represents the traditional view that rising oxygen levels, warm shallow seas, and phytoplankton expansion provided the physiological headroom for larger bodies and active metabolisms (Butterfield, 2007; Stockey et al., 2024; Zhang et al., 2014, 2025). However, in the context of our model, these conditions primarily acted as an intensity amplifier: (A) higher encounter rates accelerated the iteration rate of predation-induced genomic-stress cycles; and (B) greater physiological headroom supported the energetic cost of testing new, complex morphologies. The Cambrian was not merely a time of “more mutations” but specifically a time of more architecturally consequential genomic changes, generated at higher frequency through intensified predation stress and filtered through ecological selection for morphological disparity.
Third, Low Ecological Incumbency and Competitive Release (The Persistence Window): This factor also reflects the established understanding that simple Early Cambrian food webs offered low competitive exclusion (Budd, 2008; Butterfield, 2007; Stockey et al., 2024; Zhang et al., 2014). In our framework, this provided the essential persistence window for architectural variants (continuously generated through predation-induced genomic stress since the Ediacaran) to refine and stabilize. (A) Open niche space and (B) reduced predation pressure allowed incipient body plans the time to refine developmental programs before facing competition from more efficient forms.
The Cambrian’s low incumbency thus created an extended developmental “sandbox” where architectural variants—continuously generated through predation-induced genomic stress since the Ediacaran—could finally elaborate beyond simple prototypes into the phylum-level diversity observed in the fossil record. Additionally, the Cambrian arms race between predators and prey is selected specifically for morphological divergence rather than convergence. Rising predation pressure favored defensive innovations (exoskeletons, protective spines, burrowing), evasive strategies (directed swimming, rapid escape responses), and resource partitioning (different feeding modes accessed through different body architectures). This ecological context—where novelty itself conferred survival advantage—meant that different Hox cluster arrangements, symmetric patterns, and appendage architectures were all potentially viable solutions to the same ecological challenges. The result was divergent morphological evolution producing phylum-level disparity, rather than convergent evolution producing optimal solutions. This explains why the Cambrian generated multiple distinct architectural solutions (arthropod segmentation, molluscan modularity, chordate axial patterning) to the challenges of multicellular life, rather than a single optimal design.
Unlike modern oceans—characterized by high incumbency and complex predator–prey networks that block fundamentally novel entrants—the Cambrian offered ecological space for major innovations. Together, these conditions created a “Goldilocks” moment that enabled and amplified genomic innovation, yielding the observed diversification of animal body plans (Figure 2).
4.2 Why not other times? Constraints on repeated radiations
Two comparisons show why animal-like radiations are rare. First, Paleoproterozoic “non-radiation.” Despite the Great Oxidation Event (~2.4 Ga) supplying oxygen and productivity, no animal-like radiation occurred because the first eukaryotes (LECA)—and certainly UHP—had likely not yet evolved. This comparison confirms that geochemical change alone is insufficient to trigger a body-plan radiation (Betts et al., 2018; Brocks and Summons, 2003; Holland, 2006; Li et al., 2025; Zhang et al., 2014). Second, post-Cambrian ecosystems. Although the underlying molecular mechanisms (e.g., phagotrophy, DNA repair) persist and conditions still support large, active organisms, high ecological incumbency and complex food webs now raise an impassable barrier to founding new phyla. The capacity for macroevolutionary novelty—the formation of new phyla (disparity)—was uniquely available during the Cambrian’s low-incumbency window. In contrast, later diversification events, such as post-extinction radiations, generated massive increases in species diversity but generally occurred within the established architectural constraints of the phyla that originated in the Cambrian.
This asymmetry explains why only one major animal-like diversification occurred. By the late Ediacaran, UHP variants and possibly other mechanisms generated precursor cells had already passed the key genetic and cellular filters; Cambrian ecosystems then amplified their retention and elaboration. When the Cambrian “Goldilocks” emerged, it both (1) increased predator–prey encounter frequencies, raising the iteration rate of predation-induced genomic innovation, and (2) provided the ecological room for novel variants to persist long enough to elaborate into stable multicellular architectures (Figure 2).
5 Testable predictions and research directions
If failed phagocytosis once built the eukaryotic domain via mitochondrial EGT, it is not speculative but expected that repeated failed predation among early holozoans could have built the animal kingdom through cycles of genomic upheaval and selective stabilization. This hypothesis yields two complementary, testable predictions linking mechanistic cell biology to macroevolutionary patterns. Within the Cambrian “Goldilocks” context, use a paired approach: a mechanistic cell biology assay (5.1) and a comparative genomics screen (5.2).
5.1 Experimental test: does failed predation generate heritable variation?
5.1.1 Approach
Co-culture a mechanistically appropriate phagotrophic predator–prey system (e.g., a protist predator and a non-walled eukaryotic prey) under geochemically constrained Ediacaran–Cambrian conditions: hypoxia (2–10% PAL O2), 15–32 °C, and elevated Fe²+/Cu²+ (Reinhard et al., 2016; Sperling et al., 2013). This is a tractable analog of early holozoan–holozoan encounters.
5.1.2 Controls
Predator-only and prey-only monocultures, non-phagotrophic systems (e.g., algae with comparable generation times), and modern high-oxygen controls—all under identical conditions to isolate phagocytosis-specific effects.
5.1.3 Readouts and analysis
Select survivors showing stable, heritable proliferation for ≥15 generations; pre-screen for DNA-damage markers (e.g., γH2AX, 8-oxoG); perform single-cell whole-genome sequencing. Quantify structural variants, aneuploidy, and breakpoint clustering in phagocytic survivors vs. controls, using long-read or duplex sequencing where possible and bioinformatic filters to mitigate WGS artifacts (e.g., chimeric reads, amplification bias).
5.1.4 Prediction
Failed predation yields higher frequencies of chromosomal rearrangements and novel gene combinations in survivors, with molecular signatures of error-prone repair—absent in environmental controls.
5.1.5 Evolutionary significance
Positive results would demonstrate that predator–prey interactions can function as evolutionary accelerators, generating heritable variation above background mutation rates and empirically validating the cellular engine proposed by the Predation–Motility Hypothesis.
5.2 Comparative test: do early animal genomes show predicted signatures?
5.2.1 Approach
Using chromosome-scale reconstructions of ancestral metazoan genomes (Simakov et al., 2022), test whether structural-variant motifs identified in 5.1—especially those linked to non-homologous end joining, fusion-with-mixing, and clustered breakpoints—are enriched near genes for cell adhesion, signaling, and developmental regulation in early-branching metazoans.
5.2.2 Analyses
Examine chromosome-scale genomes of early-branching animals (sponges, ctenophores, placozoans) and their single-celled relatives for: A) clustering of breakpoints near adhesion/signaling/developmental genes; B) molecular signatures of stress-induced repair; and C) contrasts with non-phagotrophic lineages (algae, plants, fungi).
Control for phylogenetic distance, baseline rearrangement rates, and conserved synteny. Use phylogenetically controlled analyses to distinguish burst-like reorganization in the animal stem lineage from gradual background accumulation.
5.2.3 Prediction
Early animal genomes show (i) non-random clustering of rearrangements near developmental control loci, (ii) excess rearrangements relative to lineages lacking phagotrophic ancestry, and (iii) molecular signatures matching 5.1. Phagocytosis-associated variants are predicted to cluster within conserved metazoan chromosomal units but not within algal genomes lacking these ecological and mechanistic contexts.
5.2.4 Evolutionary significance
Confirmation of these signatures would link cell-level mechanisms to macroevolutionary transitions, bridging experimental and comparative lines of evidence for predation-induced genome innovation.
5.2.5 Challenges
Fragmented assemblies in non-model taxa; separating ancient burst-like events from gradual change; potential confounding factors such as lineage-specific whole-genome duplications and horizontal gene transfer. Nonetheless, coupling 5.1 and 5.2 offers a tractable strategy to test whether failed predation could truly serve as the generative engine of the Cambrian radiation.
6 Integration with existing evolutionary hypotheses
The Cellular Predation–Motility hypothesis provides a concrete ecological mechanism for the initial surge of genomic novelty that underpinned the Cambrian radiation, integrating several existing frameworks into a unified view of animal origins. In this model, repeated failed predation within the ancestral UHP lineage generated localized cellular stress, producing heritable genomic rearrangements, while motility determined which lineages repeatedly experienced these events. This interaction yielded a long-term accumulation of genetic novelty that preceded the diversification of multicellular animals.
Established explanations for Cambrian disparity—such as GRN co-option and duplication (Carroll, 2008; Simakov et al., 2013; Srivastava et al., 2010) and ecological arms-race models (Bengtson, 2002; Erwin et al., 2011; Sperling et al., 2013)–describe how morphological variants were elaborated and stabilized but assume a prior reservoir of genomic raw material. The Predation–Motility framework identifies the origin of that substrate. Cycles of failed phagocytosis triggered error-prone repair, transient chimerism, and TE activation (Galhardo et al., 2007), generating bursts of mosaic genomes and chromosomal rearrangements. These processes produced a pre-Cambrian genomic toolkit—expanded adhesion, signaling, and stemness gene families, early regulatory modularity, and TE-mediated innovation—that carried latent potential for constructing tissues, axes, and organ systems. This architectural potential could only be expressed and amplified once Cambrian ecological conditions permitted rapid elaboration.
This genomic substrate subsequently interacted with ecological selection, developmental modularity, and cis-regulatory evolution (Hammarlund et al., 2018; Hynes and Zhao, 2000). In this integrated view, environmental permissiveness and developmental complexity acted as amplifiers of diversification rather than its initiators. Rising oxygen and productivity created physiological capacity, and ecological openness allowed morphological experimentation, enabling developmental systems to translate predation-driven genomic variation into morphological novelty.
Early holozoans and the UHP lineage—phagotrophic, motile, and lacking rigid cell walls—were uniquely positioned to exploit this genomic instability. Unlike plants or fungi, which evolved barriers that limited such interactions, these ancestors could convert phagocytosis-induced crises into evolutionary opportunity. Operating within the Cambrian ecological window, this internal genomic engine helps explain the exceptional tempo and scope of early animal diversification (Martin et al., 2015).
7 Limitations and future directions
This hypothesis offers a mechanistic framework consistent with the apparent uniqueness of the Cambrian radiation to metazoans, but important uncertainties remain. Comparable bursts of genomic innovation in other phagotrophic lineages (e.g., vampyrellid amoebae, predatory fungi) may be limited by different combinations of factors including specific innovations in the holozoan stem lineage (adhesion and stemness control), cellular architecture (rigid cell walls restricting membrane dynamics in many fungi), variation in DNA-repair-pathway use and tolerance for aneuploidy or structural-variant burden, and ecological context influencing the frequency of incomplete eukaryote–eukaryote encounters.
Direct fossil evidence for phagocytosis-linked heritable genomic change is unlikely. As with other cellular-level processes, inference must rely on comparative genomics and modern analog systems rather than direct preservation.
Background sources of rearrangement, assembly and annotation heterogeneity, phylogenetic non-independence, and limited taxonomic sampling all complicate inference. Accordingly, 5.1 experiments should employ controlled predator–prey assays with preregistered structural-variant (SV) readouts and rigorous environmental controls, while 5.2 comparative analyses should apply long-read, phylogenetically corrected methods to test for non-random clustering or motif enrichment near adhesion, signaling, and developmental loci. Targeted validation using short-read re-assembly or lineage-tracing approaches would further refine results. Together, these complementary tests aim to discriminate true clustered, burst-like genomic signatures—predicted outcomes of failed-predation stress—from background noise, providing a falsifiable and data-driven path forward.
8 Conclusion
The Cambrian radiation was not a single event but the culmination of a long evolutionary sequence linking cellular ecology to organismal complexity. In our model, repeated failed predation among unicellular holozoans generated the Unicellular-grade Holozoan Precursor (UHP)—a lineage that passed three key filters: metabolic autonomy, replicative stability, and motility. These predation-driven stress cycles produced the genomic novelty—structural rearrangements, gene-family expansions, early regulatory modularity, and TE activation—that accumulated over hundreds of millions of years.
Motility then acted as the critical evolutionary filter (Figure 2), sorting lineages into high-motility forms that retained unicellularity and low-motility forms that were repeatedly exposed to predation stress and favored adhesion, cooperation, and multicellularity. This process transformed cellular vulnerability into a persistent engine of genomic innovation.
When the Cambrian “Goldilocks” conditions emerged—rising oxygen, increased productivity, and low ecological incumbency, the elevated encounter rates amplified genomic-stress cycles, while ecological openness permitted newly generated variants to persist long enough to elaborate tissues, axes, and integrated body plans. In essence, cellular predation supplied the genomic raw material, and Cambrian ecological conditions unlocked its architectural potential, enabling the rapid rise of animal body-plan disparity.
Data availability statement
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.
Author contributions
LZ: Methodology, Project administration, Validation, Formal Analysis, Writing – review & editing, Data curation, Funding acquisition, Visualization, Investigation, Writing – original draft, Conceptualization, Resources.
Funding
The author(s) declared that financial support was not received for this work and/or its publication.
Conflict of interest
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The author LZ declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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Keywords: Cambrian explosion, evolutionary innovation, genomic driver, genomic instability, multicellularity, phagocytosis, predation
Citation: Zhang L (2026) Cellular predation and motility as drivers of animal origins and the Cambrian radiation. Front. Ecol. Evol. 13:1736160. doi: 10.3389/fevo.2025.1736160
Received: 30 October 2025; Accepted: 02 December 2025; Revised: 02 December 2025;
Published: 07 January 2026.
Edited by:
Haijun Song, China University of Geosciences Wuhan, ChinaReviewed by:
Mark McMenamin, Mount Holyoke College, United StatesXingliang Zhang, Northwest University, China
Copyright © 2026 Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Luwen Zhang, bHpoYW5nMkBuZWJyYXNrYS5lZHU=