Rapid evolution of a novel signalling mechanism by concerted duplication and divergence of a BMP ligand and its extracellular modulators

Abstract

Gene duplication and divergence is widely considered to be a fundamental mechanism for generating evolutionary novelties. The Bone Morphogenetic Proteins (BMPs) are a diverse family of signalling molecules found in all metazoan genomes that have evolved by duplication and divergence from a small number of ancestral types. In the fruit fly Drosophila, there are three BMPs: Decapentaplegic (Dpp) and Glass bottom boat (Gbb), which are the orthologues of vertebrate BMP2/4 and BMP5/6/7/8, respectively, and Screw (Scw), which, at the sequence level, is equally divergent from Dpp and Gbb. It has recently been shown that Scw has arisen from a duplication of Gbb in the lineage leading to higher Diptera. We show that since this duplication event, Gbb has maintained the ancestral BMP5/6/7/8 functionality while Scw has rapidly diverged. The evolution of Scw was accompanied by duplication and divergence of a suite of extracellular regulators that continue to diverge together in the higher Diptera. In addition, Scw has become restricted in its receptor specificity: Gbb proteins can signal through the Type I receptors Thick veins (Tkv) and Saxophone (Sax), while Scw signals through Sax. Thus, in a relatively short span of evolutionary time, the duplication event that gave rise to Scw produced not only a novel ligand but also a novel signalling mode that is functionally distinct from the ancestral Gbb mode. Our results demonstrate the plasticity of the BMP pathway not only in evolving new family members and new functions but also new signalling modes by redeploying key regulators in the pathway.

Adaptive protein divergence of BMP ligands takes place under developmental and evolutionary constraints

“…Previous studies address the question of how the Scw and Gbb ligands are differentially utilized for developmental processes in different contexts (Fritsch et al, 2010;Matsuda and Shimmi, 2012). Since both proteins are categorized as BMP5-8 type ligands, we wondered whether changes in protein structure can affect the respective signaling activities of Gbb and Scw.…”

“…Signaling of N-glycosylation-modified Gbb and Scw ligands in the embryo and pupal wing scw can rescue gbb mutants in the context of PCV formation in a nonreciprocal manner (Fritsch et al, 2010;Matsuda and Shimmi, 2012). It is not clear whether structural changes of ligands lead to contextspecific properties, or whether ligands are differentially produced or secreted.…”

“…In Drosophila, gbb expression is not observed in the early embryo, but Gbb plays a crucial role in posterior crossvein (PCV) formation during the pupal stage, at which an analogous mechanism utilizing a Gbb:Dpp heterodimer is needed for BMP signaling (Shimmi et al, 2005a;Matsuda and Shimmi, 2012;Shimmi and Newfeld, 2013). Intriguingly, it has been found that Scw can restore the wild-type phenotype in crossveinless gbb mutant wings, whereas Gbb cannot replace Scw in the early embryo (Fritsch et al, 2010;Matsuda and Shimmi, 2012). Therefore, as co-factors of the BMP network, the paralogs Gbb and Scw provide a unique model to understand protein divergence of signaling molecules.…”

Position matters: Variability in the spatial pattern of BMP modulators generates functional diversity

“…BMP/Dpp Against the Source: Lessons From Planarians, Spiders, Crustaceans, and Beetles Recent analysis of BMPs and its modulators in planarians (Lophotrochozoan), echinoderms (basal deuterostome), spiders, crustaceans, and beetles (arthropods) have broadened our understanding of the role of this pathway during embryogenesis (Akiyama-Oda and Oda, 2006;Duboc et al, 2004;Fritsch et al, 2010;Gavino and Reddien, 2011;Lapraz et al, 2009;Molina et al, 2011;Nunes da Fonseca et al, 2010;Park et al, 2010;Reddien et al, 2007;Saina et al, 2009;van der Zee et al, 2006). In all these studies not only dpp expression was analyzed, but also the activity of Dpp signaling using antibodies against pMad was visualized.…”

“…Interestingly, Dpp activity is detected far from its site of mRNA expression in all animals investigated so far. At least in spiders, beetles and echinoderms (Akiyama-Oda and Oda, 2006;Fritsch et al, 2010;Lapraz et al, 2009;Molina et al, 2007;Nunes da Fonseca et al, 2010;Reddien et al, 2007;van der Zee et al, 2006) the transport of Dpp is dependent on Sog/Chd orthologs, similar to what has been described in flies (Decotto and Ferguson, 2001;Eldar et al, 2002;Shimmi and O'Connor, 2003;Wang and Ferguson, 2005) and Xenopus (Ben-Zvi et al, 2008). It is possible that additional kernel elements (tsg and tld) are also involved in Dpp transport in other animals as we have shown in the beetle Tribolium castaneum (Nunes da Fonseca et al, 2010).…”