Developmental gene regulatory network architecture across 500 million years of echinoderm evolution

Abstract

Evolutionary change in morphological features must depend on architectural reorganization of developmental gene regulatory networks (GRNs), just as true conservation of morphological features must imply retention of ancestral developmental GRN features. Key elements of the provisional GRN for embryonic endomesoderm development in the sea urchin are here compared with those operating in embryos of a distantly related echinoderm, a starfish. These animals diverged from their common ancestor 520 -480 million years ago. Their endomesodermal fate maps are similar, except that sea urchins generate a skeletogenic cell lineage that produces a prominent skeleton lacking entirely in starfish larvae. A relevant set of regulatory genes was isolated from the starfish Asterina miniata, their expression patterns determined, and effects on the other genes of perturbing the expression of each were demonstrated. A three-gene feedback loop that is a fundamental feature of the sea urchin GRN for endoderm specification is found in almost identical form in the starfish: a detailed element of GRN architecture has been retained since the Cambrian Period in both echinoderm lineages. The significance of this retention is highlighted by the observation of numerous specific differences in the GRN connections as well. A regulatory gene used to drive skeletogenesis in the sea urchin is used entirely differently in the starfish, where it responds to endomesodermal inputs that do not affect it in the sea urchin embryo. Evolutionary changes in the GRNs since divergence are limited sharply to certain cis-regulatory elements, whereas others have persisted unaltered. E volution and development are both manifestations of the heritable genomic regulatory programs that determine how the morphological characters of each species are built. Regulatory control systems include large numbers of genes encoding DNA-sequence-specific transcription factors, as well as downstream genes, among the most important of which encode components of intercellular signaling systems. The role of the developmental control machinery is to organize the progressive spatial disposition of gene regulatory states as the embryo develops. Its form is that of a gene regulatory network (GRN), the architecture of which is determined by causal cis-regulatory interactions. The GRN specifies the cells where these states transiently exist and the batteries of downstream genes they will express. A syllogism leads to the evolutionary process by which morphological characters arise and diversify: the body plan of each taxon at each developmental stage consists of conserved plus novel morphological characters (with respect to its phylogenetic relatives), and morphological characters depend causally on the operations of developmental GRNs; therefore, evolutionary conservation and novelty in form must devolve from retained and novel features of GRN architecture (1, 2). However, until recently, comparative study of GRN architecture was a prescription that could not be followed, because developm...

Gene expression profiling during the embryo‐to‐larva transition in the giant red sea urchin Mesocentrotus franciscanus

“…The embryogenesis and early larval development of echinoderms involve the interactions of regulatory, structural, and functional genes that, in some cases, are highly conserved even among distantly related echinoderm species (Hinman & Davidson, 2003a,b; Hinman, Nguyen, Cameron, et al., 2003; Hinman, Nguyen, & Davidson, 2003). However, differences in skeleton formation and embryonic territories specification in this group are the result of evolutionary changes, which include gene duplications, protein function diversification, and genes co‐opted to different functions (Dylus et al., 2016; Hinman & Davidson, 2007; Hinman, Nguyen, Cameron, et al., 2003; McCauley et al., 2010, 2012).…”

“…However, differences in skeleton formation and embryonic territories specification in this group are the result of evolutionary changes, which include gene duplications, protein function diversification, and genes co‐opted to different functions (Dylus et al., 2016; Hinman & Davidson, 2007; Hinman, Nguyen, Cameron, et al., 2003; McCauley et al., 2010, 2012). Here, comparisons of early developmental transcriptomes of echinoderms revealed several proteins/genes that are highly conserved among sea urchins, sea cucumbers, and brittle stars (Figure 2b,c).…”

“…In echinoderms, for example, the unique combination of regulatory genes (e.g., transcription factors) in embryonic space and time contribute to shaping the regulatory program for larval skeletogenesis (Dylus et al., 2016; Gao & Davidson, 2008), endomesodermal (Peter & Davidson, 2010), and ectodermal specification (Nakata & Minokawa, 2009). Despite the differences in larval development in this group (e.g., pluteus‐, bipinnaria‐, and auricularia‐like larvae), comparisons of their GRN architectures have detected highly conserved orthologous regulatory genes among the extant echinoderm classes (Hinman & Davidson, 2003a,b; Hinman, Nguyen, Cameron, & Davidson, 2003; Hinman, Nguyen, & Davidson, 2003). While the network logic employed is the same in these organisms, the transcription factors underlying certain functions have been the subject of evolutionary change, resulting in gene duplications, protein function diversification, and regulatory genes co‐opted to different functions (Dylus et al., 2016; Hinman & Davidson, 2007; Hinman, Nguyen, Cameron, et al., 2003; McCauley, Weideman, & Hinman, 2010; McCauley, Wright, Exner, Kitazawa, & Hinman, 2012).…”

The topological relationship between the large-scale attributes and local interaction patterns of complex networks

“…Theoretical and experimental evidence indicates that at least some of these recurring elementary interaction patterns carry significant information about the given network's function and overall organization (1)(2)(3)(4). For example, transcriptional regulatory networks of cells (1,2,5,6), neural networks of C. elegans (2), and some electronic circuits (2) are all information processing networks that contain a significant number of feed-forward loop (FFL) motifs. However, in transcriptional regulatory networks these motifs do not exist in isolation but meld into motif clusters (7), while other networks are devoid of FFLs altogether (2).…”

NEW: Network-Enabled Wisdom in Biology, Medicine, and Health Care

“…Previous studies indicate that the architecture of biological networks is conserved through evolution (24)(25)(26), suggesting that the overall wiring diagram may be somewhat robust to changes in the contexts. If so, context-dependent risk variants will more likely induce changes to the network activity potentially by increasing or decreasing the number of edges and nodes in the network, thereby perturbing the molecular processes and biological functions defined by that network.…”