Biology subjects

Beinsteiner, B.

Publications and source records attributed to Beinsteiner, B..

3 recordsLinked to original sources

bioRxiv2025

Identification of the protein precursor for thyroid hormone synthesis in the basal chordate ascidian Styela clava

Thyroid hormones (THs) play crucial roles in development, growth, and metabolism across the animal kingdom1,2. Although the mechanism of TH synthesis in vertebrates has been well described, it remains elusive in invertebrates due to the lack of identified orthologs of the thyroglobulin (TG), the protein precursor for TH synthesis3,4. Here, we identified a functional TG protein encompassing multiple TG type 1 (Tg1)-domains, encoded by the ScTg-like gene in proto-vertebrate ascidian Styela clava based on the immunoprecipitation-mass spectrometry combined with phylogenetic and expression pattern analyses. In vitro iodination experiments demonstrated that ScTG-like has the capacity to provide hormonogenic sites for TH synthesis. Furthermore, in vivo gene knockdown of ScTg-like revealed that the larval metamorphosis was significantly inhibited as a consequence of diminished TH levels, indicating that ScTg-like is responsible for the production of endogenous TH. Additionally, an invaginated follicle-like structure was first discovered at the central anterior of the larval trunk where both ScTG-like protein and THs were deposited, suggesting that this structure serves as the location for THs synthesis and storage, functionally similar to vertebrate thyroid follicles. Moreover, we analyzed the structural features of ScTG-like protein and detected the similarly organized Tg1-containing proteins in multiple bilaterian phyla, suggesting that endogenous TH synthesis may be an ancestral, possibly synapomorphic, trait of bilaterians. Our study is the first to identify the TH protein precursor outside vertebrates by providing the direct evidence of endogenous de novo TH synthesis, which offers insights into the evolution of TG protein and the emergence of a major vertebrate endocrine system.

evolutionary biology↗

bioRxiv2024

Estimates of molecular convergence reveal pleiotropic genes underlying adaptive variation across teleost fish

Molecular convergence, where specific non-synonymous changes in protein-coding genes lead to identical amino acid substitutions across multiple lineages, provides strong evidence of adaptive evolution. Detecting this signal across diverse taxa can reveal broad evolutionary mechanisms that may not be apparent when studying individual lineages. In this study, we search for convergent substitutions in the most speciose group of vertebrates, teleost fishes. Using an unsupervised approach, we detected convergence in 89 protein-coding genes across 143 chromosomal-level genomes. To assess their functional implications, we integrate data on protein properties, gene expression across species and tissues, single-cell RNA sequencing of zebrafish embryonic development, and gene perturbation experiments in zebrafish. The convergent genes were associated with diverse processes including embryonic development, tissue morphogenesis, metabolism, and responses to hormones and heat stress. The convergent substitutions altered amino acid properties, with some occurring at functionally critical sites. Notably, only one-third of these genes were tissue-specific, while the majority were expressed across multiple tissues and cell types. Genetic perturbation data further showed that the convergent genes can affect multiple structures across diverse tissues. These results highlight the pleiotropic nature of the convergent genes. Using an evolutionary modeling approach, we show that adaptive variation tends to accumulate in genes with intermediate pleiotropy, enabling organisms to overcome selective pressures during ecological shifts. Although traditionally considered a source of constraint, we argue that adaptation via genes with intermediate pleiotropy might be particularly advantageous following periods of ecological shifts, and can potentially lead to the evolution of convergent phenotypes.

evolutionary biology↗

bioRxiv2020

A Structural Signature Motif Enlightens the Origin and Diversification of Nuclear Receptors

Nuclear receptors are ligand-activated transcription factors that modulate gene regulatory networks from embryonic development to adult physiology and thus represent major targets for clinical interventions in many diseases. Most nuclear receptors function either as homodimers or as heterodimers. The dimerization is crucial for gene regulation by nuclear receptors, by extending the repertoire of binding sites in the promoters or the enhancers of target genes via combinatorial interactions. Here, we focused our attention on an unusual structural variation of the -helix, called {pi}-turn that is present in helix H7 of the ligand-binding domain of RXR and HNF4. By tracing back the complex evolutionary history of the {pi}-turn, we demonstrate that it was present ancestrally and then independently lost in several nuclear receptor lineages. Importantly, the evolutionary history of the {pi}-turn motif is parallel to the evolutionary diversification of the nuclear receptor dimerization ability from ancestral homodimers to derived heterodimers. We then carried out structural and biophysical analyses, in particular through point mutation studies of key RXR signature residues and showed that this motif plays a critical role in the network of interactions stabilizing homodimers. We further showed that the {pi}-turn was instrumental in allowing a flexible heterodimeric interface of RXR in order to accommodate multiple interfaces with numerous partners and critical for the emergence of high affinity receptors. Altogether, our work allows to identify a functional role for the {pi}-turn in oligomerization of nuclear receptors and reveals how this motif is linked to the emergence of a critical biological function. We conclude that the {pi}-turn can be viewed as a structural exaptation that has contributed to enlarging the functional repertoire of nuclear receptors.

evolutionary biology↗