The written accounts and reasoning associated with how the species we currently use for biomedical research were selected as model systems have rarely included weighty consideration of either their evolutionary or natural histories (Alfred and Baldwin, 2015). Instead, organisms such as Drosophila, Caenorhabditis elegans, zebrafish and mice were primarily chosen as model organisms for purely practical reasons. For example, many model organisms produce large numbers of offspring, have features that make them easy to examine (such as transparent embryos), or are easy to domesticate and look after in the laboratory. Paradoxically, while this approach has been remarkably successful in advancing our understanding of life, it has also made us acutely aware of how much more biology we have yet to comprehend.
Some have argued that further research into the model organisms that dominate much of biomedical research today could fill in the many gaps that exist in our understanding of life, but these organisms give a biased and ultimately poor statistical representation of the ∼30 million species of animals that populate our planet (Brusca and Brusca, 2003). Our best chances of uncovering new biology and acquiring a truly transformative understanding of life are therefore to be found in the laboratory of nature. As technology advances and allows us to examine aspects of biology that were not previously accessible to scientific interrogation, we may want to reconsider how we choose animals as new model systems. Instead of selecting them purely on the biological attributes they conveniently exaggerate for our scientific interests, we could also consider the ecological and evolutionary histories that may have helped produce such attributes.
These considerations are particularly timely in view of current efforts to develop and characterize invertebrate model systems for studying regeneration and parasitism. Now, in eLife, Christopher Laumer of Harvard University, Andreas Hejnol of the University of Bergen and Gonzalo Giribet, also from Harvard, have unravelled the phylogenetic tree of the Platyhelminthes, which are more commonly known as the flatworms (Laumer et al., 2015).
Animals possessing bilateral symmetry are presently grouped into three main branches in the metazoan tree of life. The Deuterostomes (the evolutionary lineage to which humans belong) are represented by a number of model organisms including mice, fish, sea squirts, sea urchins and, of course, humans. The second branch, the Ecdysozoa, is presently represented in biomedical research by the fruit fly Drosophila melanogaster and the roundworm nematode C. elegans. However, the third branch, the Lophotrochozoa, remains among the most undersampled and understudied collection of complex organisms on the planet. This is despite the fact that it encompasses a collection of animals with an assortment of body plans, biological attributes, and ecological adaptations that is unmatched by the other two bilaterian metazoan branches combined. Within the Lophotrochozoa, no group of animals manifests these attributes as clearly as the Platyhelminthes: the diversity of body plans, developmental plasticity and ecological adaptations displayed by these flatworms is remarkable.
Laumer, Hejnol and Giribet report on a comprehensive analysis of the evolutionary relationships among the Platyhelminthes using a survey of genomes and transcriptomes that represents all free-living (i.e., non-parasitic) flatworm orders. This work is the first of its type for the Platyhelminthes and ultimately provides a modern hypothesis that should help us to understand how this extraordinarily diverse group of animals evolved.
By comparing hundreds of nuclear protein coding genes, Laumer et al. were able to derive a phylogeny with at least two important and intriguing attributes. Firstly, key evolutionary transitions within the Platyhelminthes unexpectedly featured the involvement of ‘microturbellarian’ (microflatworm) groups (Figure 1). Secondly, a novel scenario that explains the interrelationships between free-living and parasitic flatworms provides unique opportunities for shedding light on the origins and biological consequences of the parasitic lifestyle in these animals.
The Tricladida order of flatworms contains the important model system Schmidtea mediterranea, which is used to study tissue regeneration and development. An intriguing point raised by the phylogenetic tree produced by Laumer et al. is that this order may be evolutionarily equidistant to two other orders (Prolecithophora and Fecampiida). This new relationship will have to be taken into account from this point onward when considering how the regenerative properties displayed by these three groups of animals evolved.
The work of Laumer et al. makes it clear that we should embrace an approach that involves morphological studies, evolutionary developmental biology and evolutionary genomics when selecting organisms for experimental interrogation. The evidence reported for the importance of microturbellarians (Figure 1) in the evolution of Platyhelminthes may ultimately prove to be the single most important contribution of the present body of work. Microturbellarians have not captured the attention of researchers like the best-known branches of the clearly much larger and phylogenetically diverse flatworms (e.g., planarians, polyclads, and neodermatans). It is my suspicion that this paper will bring an end to their relative obscurity.
BookInvertebratesSunderland, Mass: Sinauer Associates.
The larynx enables speech while regulating swallowing and respiration. Larynx function hinges on the laryngeal epithelium which originates as part of the anterior foregut and undergoes extensive remodeling to separate from the esophagus and form vocal folds that interface with the adjacent trachea. Here we find that sonic hedgehog (SHH) is essential for epithelial integrity in the mouse larynx as well as the anterior foregut. During larynx-esophageal separation, low Shh expression marks specific domains of actively remodeling epithelium that undergo an epithelial-to-mesenchymal transition (EMT) characterized by the induction of N-Cadherin and movement of cells out of the epithelial layer. Consistent with a role for SHH signaling in regulating this process, Shh mutants undergo an abnormal EMT throughout the anterior foregut and larynx, marked by a cadherin switch, movement out of the epithelial layer and cell death. Unexpectedly, Shh mutant epithelial cells are replaced by a new population of FOXA2-negative cells that likely derive from adjacent pouch tissues and form a rudimentary epithelium. These findings have important implications for interpreting the etiology of HH-dependent birth defects within the foregut. We propose that SHH signaling has a default role in maintaining epithelial identity throughout the anterior foregut and that regionalized reductions in SHH trigger epithelial remodeling.
As a first step in innate immunity, pattern recognition receptors (PRRs) recognize the distinct pathogen and herbivore-associated molecular patterns and mediate activation of immune responses, but specific steps in the evolution of new PRR sensing functions are not well understood. We employed comparative genomic and functional analyses to define evolutionary events leading to the sensing of the herbivore-associated peptide inceptin (In11) by the PRR inceptin receptor (INR) in legume plant species. Existing and de novo genome assemblies revealed that the presence of a functional INR gene corresponded with ability to respond to In11 across ~53 million years (my) of evolution. In11 recognition is unique to the clade of Phaseoloid legumes, and only a single clade of INR homologs from Phaseoloids was functional in a heterologous model. The syntenic loci of several non-Phaseoloid outgroup species nonetheless contain non-functional INR-like homologs, suggesting that an ancestral gene insertion event and diversification preceded the evolution of a specific INR receptor function ~28 my ago. Chimeric and ancestrally reconstructed receptors indicated that 16 amino acid differences in the C1 leucine-rich repeat domain and C2 intervening motif mediate gain of In11 recognition. Thus, high PRR diversity was likely followed by a small number of mutations to expand innate immune recognition to a novel peptide elicitor. Analysis of INR evolution provides a model for functional diversification of other germline-encoded PRRs.