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The origin and evolution of cell types

Key Points

  • A new evolutionary definition of cell types is presented. Cell types are evolutionary units defined by common descent rather than phenotypic similarity, and characterized by their ability to evolve gene expression programmes independently of each other.

  • The evolutionary diversification of cell types is driven by genomic individuation, which increases the capacity of sister cell types to establish and maintain distinct gene expression programmes.

  • Core regulatory complexes (CoRCs) of terminal selectors determine cell type identity. CoRCs are the molecular agents that enable cell type-specific gene expression.

  • Apomeres are new cellular modules or variants of modules in incipient sister cell types that implement cell type-specific structure and functions.

  • Concerted evolution is characteristic for related cell types that share some genomic information, such as genes or shared enhancers.

  • The evolutionary lineage of cell type individuation is different from the developmental lineage. Serial sister cell types that develop from distinct developmental regions are closely related in evolution but differ in developmental lineage.

Abstract

Cell types are the basic building blocks of multicellular organisms and are extensively diversified in animals. Despite recent advances in characterizing cell types, classification schemes remain ambiguous. We propose an evolutionary definition of a cell type that allows cell types to be delineated and compared within and between species. Key to cell type identity are evolutionary changes in the 'core regulatory complex' (CoRC) of transcription factors, that make emergent sister cell types distinct, enable their independent evolution and regulate cell type-specific traits termed apomeres. We discuss the distinction between developmental and evolutionary lineages, and present a roadmap for future research.

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Figure 1: Evolution of phenotypic similarity.
Figure 2: The regulatory signature of cell type identity.
Figure 3: Sister cell types evolve by individuation.
Figure 4: Evolution of pre- and postsynaptic apomeres by module integration and divergence.
Figure 5: Interrelationship of developmental and evolutionary cell type lineages.

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Acknowledgements

This paper resulted from discussions of a working group at the Santa Fe Institute (SFI), New Mexico, USA, sponsored by the Arizona State University (ASU)-SFI Center for Biosocial Complex Systems. The authors are grateful for their support. Research on neuron type evolution in the Arendt laboratory is financially supported by a European Research Council Advanced grant (294810 Brain Evo-Devo). Research on cell type origination in the Wagner laboratory is financially supported by a grant from the John Templeton Foundation (grant no. 54860). The opinions expressed in this article are not those of the John Templeton Foundation.

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Correspondence to Detlev Arendt, Manfred D. Laubichler or Günter P. Wagner.

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PowerPoint slides

Glossary

Cellular modules

Protein complexes, pathways and molecular machines that make up cell structure and function.

Cell type homology

Cell types that trace back to the same cell type in a common ancestor.

Cell phenotypic convergence

Cell types that are phenotypically similar due to independent changes occurring in separate evolutionary lineages.

Concerted evolution

Similar phenotypic changes that occur simultaneously across different cell types of the same species as a result of altering genetic information shared among the cell types.

Sister cell types

Cell types arising by the splitting of an ancestral cell type into two descendant cells via the process of individuation.

Evolutionary units

Modular biological entities capable of evolving as a cohesive unit and at least partially independently of others (for example, genes, cell types and species).

Genetic individuation

The evolutionary independence of cell types resulting from the differential use of genomic information.

Core regulatory complex

(CoRC). A protein complex composed of terminal selector transcription factors that enables and maintains the distinct gene expression programme of a cell.

Terminal selectors

A set of transcription factors that directly regulates the cell type-specific set of effector genes and represses alternative cell type identities.

Apomeres

Derived cell type-specific cellular modules.

Synapomeres

Ancestral apomeres now shared by descendant sister cell types.

Pan-neuronal genes

Genes expressed broadly, but not exclusively, in neurons; for example, synaptic and vesicular genes.

Module integration

Evolution of a new functional complex or pathway by colocalization and integration of pre-existing functional machinery.

Module divergence

Evolution of cell type-specific variation in protein complexes or pathways; commonly occurs by gene duplication and divergence.

SNARE

Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein (SNAP) receptor.

Cell type fusion

Co-option of a second core regulatory complex into an existing cell type, creating a cell type hybrid of two different ancestral cell type identities.

Serial sister cell types

Sister cell types that arise from different developmental lineages or regions of the body.

Sensory placodes

Thickened patches of embryonic head ectoderm that contribute sensory receptor cells, secretory cells and supporting cells to peripheral sense organs, and/or sensory neurons to cranial ganglia.

Comparative connectomics

A research programme comparing the neuronal connection networks between species.

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Arendt, D., Musser, J., Baker, C. et al. The origin and evolution of cell types. Nat Rev Genet 17, 744–757 (2016). https://doi.org/10.1038/nrg.2016.127

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