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Cell type evolution

Cell type evolution is the study of the molecular mechanisms of cell type origins and diversification in multicellular organisms.

Animal cell types

Animal lineages of more recent evolutionary origin are known to have a greater diversity of cell types, a trend that can be traced back to the most basal branches of animal life. While sponges have very few defined cell types, the human body contains hundreds. But how did cell type diversity evolve?

Cell types have historically been defined phenotypically and morphologically using a combination of microscopy and histology, allowing for the identification of seemingly homologous cell types between closely and distantly related animal phyla. From an evolutionary perspective, this is problematic because phenotypic similarity does not imply homology. Additional means of evolving phenotypic similarity include convergent and concerted (parallel) evolution. More recently, molecular techniques have been used to study the molecular signatures of cell type identity to further clarify ambiguous cases of cell type homology.

Additionally, it has been proposed that a cell type’s unique regulatory signature can be used to better compare cell types within and between animals. This is due to the fact that while different cell types might acquire lineage-specific phenotypic features, their identities, although fragmented, can be discerned by the evolutionary conservation of distinct regulatory mechanisms.

In this light, cell type homology stays true to the original definition formerly put forth by Richard Owen in 1843 regarding homologous relationships between organs:

“...the same organ in different animals under every variety of form and function.”

Molecular mechanisms of cell type identity

A cell type identity is what is what makes cell types unique. A cell type is differentiated by its unique pattern of gene expression, also called its cell type identity network (CIN). The following features are common mechanisms recognized across different studies of cell type evolution:

• A CIN that includes a specific combination of regulators including transcription factors and non-coding RNAs.
• A core complex of regulators that form regulatory units known as core regulatory complexes (CoRCs).
• A shallow hierarchical network of between core regulatory genes and the effector genes that determine cell phenotype, which are often directly regulated by the former.
• A positive feedback loop formed by the CoRC such that the network of regulatory components maintains its own expression and decouples itself from cell fate inducing signals.
• A maintenance of cell type identity through the active suppression of alternative identities at the level of cross-antagonism between the core regulatory networks or in suppressing alternative sets of effector genes or both.

The sister cell type model

Ancient cell types tend to have multiple functions. This model of cell type evolution posits that emergent sister cell types are the result of functional segregation and specialization of a multifunctional ancestral cell type. This process of genetic individuation can occur through changes in any of the characteristics of cell type identity, leading to the realization of a new CIN.

Apomeres are groups of effector genes that, once expressed as proteins, work together to perform a particular function for the cell. They represent the molecular machinery present within a cell and different combinations of these molecular machines give rise to different functionality. The formation, integration, and divergence of apomeres is a good example of modularity in cell type evolution. An individual apomere can be expressed and reused in multiple cell types. However, it is ultimately the combination of apomeres that gives specificity to a cell type phenotype.

Cell types evolve through novel CIN realizations. The mechanisms by which CINs evolve include:

• The formation of a new or modification of an already existing core regulatory complex.
• The gain or loss of a cellular module, also known as an apomere.
• The integration of previously existing apomeres into a single apomere.
• The divergence of an apomere into two new apomeres.

An important assumption of the sister cell type model is the decoupling of cell type evolution from cell type development. While conservation of mechanisms in cell type development between species can be used as evidence for homology, there are examples where developmental pathways have been altered, while cell type identity has not, leading to a heterogenous distribution of cell types throughout an adult animal body. [6] An example of diverged developmental mechanisms that give rise to similar cell types is the vulval cell type in nematodes.

Further reading

• Structural evolution of cell types by step-wise assembly of cellular modules - review of several well studied cell types and their suggested origins