Morphological Evolution Repeatedly Caused by Mutations in Signaling Ligand Genes

Abstract

What types of genetic changes underlie evolution? Secreted signaling molecules (syn. ligands) can induce cells to switch states and thus largely contribute to the emergence of complex forms in multicellular organisms. It has been proposed that morphological evolution should preferentially involve changes in developmental toolkit genes such as signaling pathway components or transcription factors. However, this hypothesis has never been formally confronted to the bulk of accumulated experimental evidence. Here we examine the importance of ligandcoding genes for morphological evolution in animals. We use Gephebase (http:// www.gephebase.org), a database of genotype-phenotype relationships for evolutionary changes, and survey the genetic studies that mapped signaling genes as causative loci of morphological variation. To date, 19 signaling genes represent 20% of the cases where an animal morphological change has been mapped to a gene (80/391). This includes the signaling gene Agouti, which harbors multiple cis-regulatory alleles linked to color variation in vertebrates, contrasting with the effects of coding variation in its target, the melanocortin receptor MC1R. In sticklebacks, genetic mapping approaches have identified 4 signaling genes out of 14 loci associated with lake adaptations. Finally, in butterflies, a total of 18 allelic variants of the WntA Wnt-family ligand cause color pattern adaptations related to wing mimicry, both within and between species. We discuss possible hypotheses explaining these cases of natural replication (genetic parallelism) and conclude that signaling ligand loci are an important source of sequence variation underlying morphological change in nature.

Gephebase, a Database of Genotype-Phenotype Relationships for natural and domesticated variation in Eukaryotes

“…These datasets have been used by various authors to highlight several trends regarding the genetic basis of natural variation. For example, based on these compilations it was found that the mutations responsible for long-term evolution have distinct properties than the mutations responsible for short-term evolution (1,10) , that certain types of mutations are more likely to be fixed than others during the course of evolution (11) , that independent evolution of similar traits in distant lineages often involves mutations in the same orthologous gene (2) , that current data are biased towards a limited number of model organisms (12) , and that the cis-regulatory tinkering of signaling ligand genes is a recurring mode of morphological evolution (13) .…”

Leopards and giants, tigers and woolly bears: casting a broader net in exploring heparin effects on Lepidoptera wing patterns

“…et al There is more than one Wnt ligand. As reported in (Martin and Reed, 2014 ) and as discussed in (Martin and Courtier-Orgogozo, 2017 ), there are at least 4 different Wnt ligands that are expressed in the developing butterfly wing during color pattern determination, with wingless (wg) and WntA perhaps being the most important. On the whole, it appears that heparin has a much greater effect on phenoytpes associated with WntA signaling than on phenotypes associated with wg signaling.…”

“…Regarding: "Marginal eyespots in many Nymphalidae are concentrically organized and serve as models for studies of development, as for example, in Bicyclus anynana, where they have been shown to be positively regulated by Wingless (Wnt) (Özsu et al, 2017 ). Wnt signaling delimits the boundaries of wing spots, as reviewed by Martin & Courtier-Orgogozo.,2017 , and is affected by heparin. Figure 4(Aiii-Diii) suggests that, even though the serial border spots of the tawny emperor are not as concentrically organized as in many other nymphalids, they are nevertheless homologous.…”

The coding loci of evolution and domestication: current knowledge and implications for bio-inspired genome editing

“…In other words, the key for understanding biodiversity and improving varieties is to find the link between phenotype and genotype (Hufford et al, 2019). To summarize the breadth of knowledge about the genes and the mutations responsible for natural and domesticated variation, we created the database Gephebase (contraction of genotype-phenotype database), available at gephebase.org (Courtier-Orgogozo et al, 2020;Martin and Courtier-Orgogozo, 2017). This database compiles published genotype-to-phenotype relationships, defined here as a DNA sequence variation causing an observable trait variation (Orgogozo et al, 2015), in a variety of organisms.…”