A topological look into the evolution of developmental programs

Abstract

Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describing the intertwined network of spatiotemporal processes underlying the development of complex multicellular organisms. Nonetheless, an overview of developmental trajectories can be obtained from cell type lineage maps. Here, we propose that these lineage maps can also reveal how developmental programs evolve: the modes of evolving new cell types in an organism should be visible in its developmental trajectories and therefore in the geometry of its cell type lineage map. This idea is demonstrated using a parsimonious generative model of developmental programs, which allows us to reliably survey the universe of all possible programs and examine their topological features. We find that, contrary to belief, tree-like lineage maps are rare, and lineage maps of complex multicellular organisms are likely to be directed acyclic graphs in which multiple developmental routes can converge on the same cell type. Although cell type evolution prescribes what developmental programs come into existence, natural selection prunes those programs that produce low-functioning organisms. Our model indicates that additionally, lineage map topologies are correlated with such a functional property: the ability of organisms to regenerate.

Figure 1

Cell type lineage maps (CTLMs). In (A) and (B), gray circles represent cell states of unicellular organisms, and arrows represent changes in cellular phenotype. In (C) and (D), the blue circles represent cell types of multicellular organisms, and arrows represent differentiation. (A) The life cycle of the unicellular organism Creolimax fragrantissima involves cycling between three stages: a motile amoeboid state, the immobile cyst state, and the multinucleate coenocyte (12). (B) Capsaspora owkzarzaki responds to environmental cues to switch between three cell-states: cells switch from a reproductive amoeboid state to an aggregative multicellular state in the presence of nutrients, and both the amoeboid and multicellular cell states switch to a cyst state under starvation (12). (C) The CTLM for both embryonic development and adult homeostasis of V. carterii (4). (D) The CTLM representing adult homeostasis in hydra (13). Empty circles represent unannotated intermediate cell types. To see the figure in color, go online.

Figure 2

Evolution of GRN in mammals leads to the invention of a new cell type. Blue circles represent cell states, and bold arrows represent a change in cell state. Dashed gray arrows represent evolutionary transitions. Dotted black arrows represent the application of stress signal. In the ancestor of marsupials (nonplacental) and placental mammals, paleo-ESF cells responded to stress signals by elevating the expression of genes associated with stress responses and apoptosis. The stressed cell state then relaxes back into the normal paleo-ESF cell. But in placental mammals, a rewiring of the regulatory network led to the invention of two new cell types: the neo-ESF and the DSC cells. The neo-ESF cell, upon receiving stress signals, differentiates into the DSC cell instead of expressing stress response genes (33). To see the figure in color, go online.

Figure 3

Generative model of biological development. Blue circles represent cell states, and numbers written inside them represent the identity of cell states; 0 represents the absence, and 1 represents the presence of a cell-state determinant. Solid arrows represent change in the cell state, and dashed arrows represent the exchange of signaling molecules. (A)–(C) represent the regulatory architecture of an organism with N = 2 determinants. (A) Asymmetric cell division: cell types in the model can produce daughter cells that are not identical. (B) Cell signaling: certain cell-state determinants can act as signals and are secreted by donor cells and received by specific acceptor cells. In this example, the first determinant is a signal. The state of the acceptor cell reflects signal reception by switching the state of signal determinant to “1.” (C) Gene regulation: certain cell states are stable cell types, and others are transient cell states that map to the stable cell types. (D) Scheme of development in the model: the zygote undergoes repeated rounds of asymmetric cell division, cell-cell signaling, and gene regulation according to the rules outlined in (A)–(C). The grey dashed boxes indicate one repeat of cell division, cell signaling and gene regulation steps. The process is iterated until the resulting set of cell types repeats itself; this set of cell types forms the adult. (E) CTLM of adult homeostasis: in this example, the two cell types constitute the adult produced by the developmental program sketched in (D). The arrows represent differentiation. To see the figure in color, go online.

Figure 4

Prevalence of topologies and their regenerative capacities. (A) Graph topologies of CTLMs. The numbers beside the graphs indicate their prevalence in our data. (B) Distribution of regenerative capacities of organisms with different CTLM topologies is represented by the distribution of points in the swarms. To see the figure in color, go online.