A review of carcinization: from the biology to computational models

COURTESY: 10 Reasons to Celebrate Darwin Day, Paleontology World, February 14, 2018.

For Darwin Day 2025, I will talk about a form of convergent evolutionary phenomenon called carcinization. Carcinization is the convergent evolution of a crab phenotype. Crablike body plans (defined by a flat, rounded shell and a tail that is folded underneath the body) evolved independently at least five times over the course of Decopod evolution (Hamers, 2023; Wolfe et.al, 2021). This is an example of convergent evolution, where similar phenotypes (and by extension functional evolution) recur in different lineages with ostensibly different underlying molecular mechanisms.

From a phylogenetic perspective, carcinization (acquisition of a crablike body plan) and decarcinization (loss of a crablike body plan) are ubiquitous across marine invertebrates. Ecological selection for such a body type that has led to phenotypic integration of multiple traits, particularly the carapace shape and abdomen (Wolfe et.al, 2021). Figure 1 shows the phylogenetic origins of carcinization in the Brachyura and Anomura clades (infraorders).

Figure 1. A phylogeny showing a variety of crab phenotypes (left), and an illustration of transformation to different crab phenotypes (right). Left image: "How Does a Crustacean Become a Crab", Phys.org. Right image: The "hermit to king" transition within the infraorder Anomura (Tsang et.al, 2011). Click to enlarge.

The most interesting attributes of the carcinization body plan involves: 1) multiple paths to a basic phenotype (shape). Many alternate genotypes result in self-similar phenotype, 2) phenotypic elaboration not due to common ancestry, and 3) a generalized form of common ancestry not at the level of traits. There are varying definitions of carcinization (or brachyurization, see Footnote 1) across genera and orders. The strict definition of McLaughlin and Lemaitre (1997) is a reduction and folding of the abdomen beneath the thorax, or the evolution of a crab-like appearance. 

We can use molecular methods to discover the deep evolutionary relationships between various instances of crab-like phenotypes. Using a mitochondrial phylogeny based on genomic rearrangements of an arthropod protein-coding gene, Morrison et.al (2002) suggest that once they appear, the independent evolution of crab-like forms may be irreversible. Another study by Wolfe et.al (2019) utilize nuclear genes and the Anchored Hybrid Enrichment (AHE) method to confirm monophyletic (single origin) relationships between all infraorders of the clade Decopoda. They also demonstrate that monophyletic "lobster" and "crab" groups exist. In terms of developmental origins, carcinization involves Brachyury (T-box Genes): great detail for its pivotal role in the development of the notochord and posterior mesoderm (Papaioannou, 2014; see also Footnote 1). Carcinization results from several transcriptional mechanisms related to physiology and phenotype, including energy metabolism-related pathways, ventral nerve cord fusion and associated apoptosis, metamorphosis, and abdominal-specific Hox genes (Yang et.al, 2021).

The evolution and development of the crab-like body plan can be characterized computationally in order to expand our understanding of convergent evolution in the evolution of development. There are a number of means to build a computational model of this process. Ostachuk (2021) proposes a network-based topological model of crab metamorphic development. In this model, the stages of brachyuran metamorphosis are modeled as a series of complex networks. Figure 2 shows this process of defining morphological unit centroids as network nodes, and topological transformations between morphological units as the network edges. A topological overlap analysis was conducted to demonstrate changes in phenotypic complexity. Traditional measures of complexity, such as modularity and hierarchical organization, increase across the course of development. This corresponds to what Ostachuk (2021) defines as a transition from intensive to extensive complexity.

Figure 2. A network of morphological units derived from a crab-like phenotype. From Figure 1B, Ostachuk, 2021. Click to enlarge.

Figure 3. A comparison of developmental network topologies from egg to crab phenotype. From Figure 3 in Ostachuk, 2021. Click to enlarge.

Ostachuk (2021) uses morphological networks rather than gene regulatory networks (GRNs) because it is difficult to make a mapping from network outputs to topological transformations of the phenotype. Yet one benefit of using genomic representations is to allow for a further representation of canalized morphogenesis. This is consistent with Waddington's notion of reduced sensitivity to genetic or environmental perturbations (Agam and Braun, 2025) and is amenable to understanding via an epigenetic landscape model. The epigenetic landscape model (Wang et.al, 2011) in particular is useful for modeling the evo-devo of carcinization. According to our evolutionary examples, we should expect the landscape to converge during development. A prediction can be made that most stable points in the epigenetic landscape favor a path towards crab-like phenotypes. Molecular mechanisms such as Hsp90 can provide a mechanism for phenotypic divergence in cavefish. Yet phenotypic buffering mechanisms can also work the other direction: multiple configurations of genomic loci converge to the same phenotype (Kovuri et.al, 2023). This phenotype tends to become irreversible as other options are no longer developmentally viable. Indeed, evolutionary irreversibility can be represented as a saddle node, a pitchfork bifurcation where two developmental pathways diverge (Ferrell, 2012).

Carcinization can also be summarized in the form of a computational genotype-phenotype map (Figure 4). On such a map, we can approximate convergent evolution as multiple genotypic representations that converge to a single phenotype. Genotype-phenotype maps also allow convergent evolution to be viewed as a study in self-similarity. In the complexity literature, self-similarity is defined as a complex system with the same statistical properties at multiple powers of magnitude (Magnusson, 2023). Figure 4 demonstrates three different types of genotype-phenotype maps: GRNs to phenotypic modules (Figure 4A), a correspondence map that maps between domains (Figure 4B), and a genotypic representation that maps to a phenotypic representation (Figure 4C). In Figure 4A, the output of three GRNs (G1, G2, G3) are mapped to four phenotypic modules (P1, P2, P3, P4). Each GRN can map their outputs to multiple phenotypic modules, components of a phenotype that we observe in the crab-like body plan. This allows us to estimate the contribution of each GRN to each phenotypic module (Wagner et.al, 2007; see also Footnote 2). Figure 4B provides a means to understand the space of genotypic variation and how this corresponds to the space of all possible phenotypic configurations. While the example we give is not specific to crab-like body plans, in such a case a wide variety of GRN activities (W_g) will correspond to a constrained set of locations in the phenotypic map (W_p). This allows us to apply more sophisticated Computational Biology models such as joint manifolds (Munteanu and Sole, 2008). To conclude, Figure 4C demonstrates the concept of phenotypic redundancy (Ahnert, 2017), which is a common feature of phenotypic maps. Phenotypic redundancy can also help us understand how multiple genotypic representations can converge upon a self-similar phenotype. Our genotypic representation contains a simple chromosome with multiple loci, which in Figure 4C are recombined and mutated across our three examples. Our phenotype is a 2-D layer of black and white cells, which result from the expression of the genotypic representation. Based on an application of theory, the crab-like body plan can be said to exhibit robustness against gene duplication, mutation, and recombination events.

Figure 4. Genotype-Phenotype map components. A) discrete model of genomic elements (containing a GRN) with their outputs mapping to different phenotypic modules, B) correspondence map showing how genotypic elements in domain W_g map to phenotypic elements in domain W_p, C) genotypic representations that converge upon a single phenotypic representation. Click to enlarge.

Let us conclude with two items for further study. Wolfe et.al (2021) asks: can you predict a phenotype from ecology or genomics? In the case of carcinization, we observe repeated gain and loss of body plan: polyphyletic nature of crab phenotype. We might also be able to predict crab-like phenotypes from the results of computational models. The developmental network and epigenetic landscape approaches are particularly promising in this regard. Might carcinization be a form of developmental buffering as predicted by the epigenetic landscape model? Patterson and Klingenberg (2007) suggest that phenotypic buffering is triggered by Hsp90 activities in flies, fish, and plants. Genotype-phenotype maps are indeed possible but require a complete characterization of the genetic diversity underlying the multitude examples of crab-like phenotypes found in nature.

Footnotes:

1. Brachyurization is perhaps related to brachyury, which involves with the epithelial-mesenchymal transition in development. A description of this process is reviewed in Huang et.al (2022) and Haerinck et.al (2023).

2. Further discussion of conducting genotype-phenotype mapping using network approaches are presented in Kim and Przytycka (2013).

References:

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Yang, Y., Cui, Z., Feng, T., Bao, C., and Xu, Y. (2021). Transcriptome analysis elucidates key changes of pleon in the process of carcinization. Journal of Oceanology and Limnology, 39, 1471–1484.