New non-bilaterian transcriptomes provide novel insights into the evolution of coral skeletomes

New Non-Bilaterian Transcriptomes Provide Novel Insights into the Evolution of Coral Skeletomes

Genome Biology and Evolution ◽

10.1093/gbe/evz199 ◽

2019 ◽

Vol 11 (11) ◽

pp. 3068-3081 ◽

Cited By ~ 5

Author(s):

Nicola Conci ◽

Gert Wörheide ◽

Sergio Vargas

Keyword(s):

De Novo ◽

Phylogenetic Analyses ◽

Organic Matrix ◽

Sensu Stricto ◽

Carbonic Anhydrases ◽

Biomineralization Process ◽

Specific Proteins ◽

Taxonomically Restricted Genes ◽

Acidic Proteins ◽

Related Proteins

Abstract A general trend observed in animal skeletomes—the proteins occluded in animal skeletons—is the copresence of taxonomically widespread and lineage-specific proteins that actively regulate the biomineralization process. Among cnidarians, the skeletomes of scleractinian corals have been shown to follow this trend. However, distributions and phylogenetic analyses of biomineralization-related genes are often based on only a few species, with other anthozoan calcifiers such as octocorals (soft corals), not being fully considered. We de novo assembled the transcriptomes of four soft-coral species characterized by different calcification strategies (aragonite skeleton vs. calcitic sclerites) and data-mined published nonbilaterian transcriptome resources to construct a taxonomically comprehensive sequence database to map the distribution of scleractinian and octocoral skeletome components. Cnidaria shared no skeletome proteins with Placozoa or Ctenophora, but did share some skeletome proteins with Porifera, such as galaxin-related proteins. Within Scleractinia and Octocorallia, we expanded the distribution for several taxonomically restricted genes such as secreted acidic proteins, scleritin, and carbonic anhydrases, and propose an early, single biomineralization-recruitment event for galaxin sensu stricto. Additionally, we show that the enrichment of acidic residues within skeletogenic proteins did not occur at the Corallimorpharia–Scleractinia transition, but appears to be associated with protein secretion into the organic matrix. Finally, the distribution of octocoral calcification-related proteins appears independent of skeleton mineralogy (i.e., aragonite/calcite) with no differences in the proportion of shared skeletogenic proteins between scleractinians and aragonitic or calcitic octocorals. This points to skeletome homogeneity within but not between groups of calcifying cnidarians, although some proteins such as galaxins and SCRiP-3a could represent instances of commonality.

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Computational design of closely related proteins that adopt two well-defined but structurally divergent folds

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914808117 ◽

2020 ◽

Vol 117 (13) ◽

pp. 7208-7215 ◽

Cited By ~ 5

Author(s):

Kathy Y. Wei ◽

Danai Moschidi ◽

Matthew J. Bick ◽

Santrupti Nerli ◽

Andrew C. McShan ◽

...

Keyword(s):

Large Scale ◽

De Novo ◽

Conformational Transition ◽

Protein Structures ◽

Computational Design ◽

Spectroscopic Characterization ◽

De Novo Design ◽

Viral Fusion ◽

Naturally Occurring ◽

Related Proteins

The plasticity of naturally occurring protein structures, which can change shape considerably in response to changes in environmental conditions, is critical to biological function. While computational methods have been used for de novo design of proteins that fold to a single state with a deep free-energy minimum [P.-S. Huang, S. E. Boyken, D. Baker, Nature 537, 320–327 (2016)], and to reengineer natural proteins to alter their dynamics [J. A. Davey, A. M. Damry, N. K. Goto, R. A. Chica, Nat. Chem. Biol. 13, 1280–1285 (2017)] or fold [P. A. Alexander, Y. He, Y. Chen, J. Orban, P. N. Bryan, Proc. Natl. Acad. Sci. U.S.A. 106, 21149–21154 (2009)], the de novo design of closely related sequences which adopt well-defined but structurally divergent structures remains an outstanding challenge. We designed closely related sequences (over 94% identity) that can adopt two very different homotrimeric helical bundle conformations—one short (∼66 Å height) and the other long (∼100 Å height)—reminiscent of the conformational transition of viral fusion proteins. Crystallographic and NMR spectroscopic characterization shows that both the short- and long-state sequences fold as designed. We sought to design bistable sequences for which both states are accessible, and obtained a single designed protein sequence that populates either the short state or the long state depending on the measurement conditions. The design of sequences which are poised to adopt two very different conformations sets the stage for creating large-scale conformational switches between structurally divergent forms.

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Mosaic origin of the eukaryotic kinetochore

10.1101/514885 ◽

2019 ◽

Author(s):

Jolien J.E. van Hooff ◽

Eelco Tromer ◽

Geert J.P.L. Kops ◽

Berend Snel

Keyword(s):

Large Scale ◽

De Novo ◽

Transport Systems ◽

Gene Duplications ◽

Homology Detection ◽

Family Reconstruction ◽

Novel Proteins ◽

Complex Protein ◽

Specific Proteins ◽

Simple Systems

AbstractThe emergence of eukaryotes from ancient prokaryotic lineages was accompanied by a remarkable increase in cellular complexity. While prokaryotes use simple systems to connect DNA to the segregation machinery during cell division, eukaryotes use a highly complex protein assembly known as the kinetochore. Although conceptually similar, prokaryotic segregation systems and eukaryotic kinetochore proteins share no homology, raising the question of the origins of the latter. Using large-scale gene family reconstruction, sensitive profile-versus-profile homology detection and protein structural comparisons, we here reveal that the kinetochore of the last eukaryotic common ancestor (LECA) consisted of 52 proteins that share deep evolutionary histories with proteins involved in a few prokaryotic processes and a multitude of eukaryotic processes, including ubiquitination, chromatin regulation and flagellar as well as vesicular transport systems. We find that gene duplications played a major role in shaping the kinetochore: roughly half of LECA kinetochore proteins have other kinetochore proteins as closest homologs. Some of these (e.g. subunits of the Mis12 complex) have no detectable homology to any other eukaryotic protein, suggesting they arose as kinetochore-specific proteins de novo before LECA. We propose that the primordial kinetochore evolved from proteins involved in various (pre-)eukaryotic systems as well as novel proteins, after which a subset duplicated to give rise to the complex kinetochore of LECA.

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Large-scale identification of encystment-related proteins and genes in Pseudourostyla cristata

Scientific Reports ◽

10.1038/srep11360 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 4

Author(s):

Xiuxia Gao ◽

Fenfen Chen ◽

Tao Niu ◽

Ruidan Qu ◽

Jiwu Chen

Keyword(s):

Molecular Mechanism ◽

Vegetative Cell ◽

Large Scale ◽

Molecular Mechanisms ◽

Qrt Pcr ◽

Resting Cyst ◽

Specific Proteins ◽

Resting Cysts ◽

Related Proteins ◽

Pseudourostyla Cristata

Abstract The transformation of a ciliate into cyst is an advance strategy against an adverse situation. However, the molecular mechanism for the encystation of free-living ciliates is poorly understood. A large-scale identification of the encystment-related proteins and genes in ciliate would provide us with deeper insights into the molecular mechanisms for the encystations of ciliate. We identified the encystment-related proteins and genes in Pseudourostyla cristata with shotgun LC-MS/MS and scale qRT-PCR, respectively, in this report. A total of 668 proteins were detected in the resting cysts, 102 of these proteins were high credible proteins, whereas 88 high credible proteins of the 724 total proteins were found in the vegetative cells. Compared with the vegetative cell, 6 specific proteins were found in the resting cyst. However, the majority of high credible proteins in the resting cyst and the vegetative cell were co-expressed. We compared 47 genes of the co-expressed proteins with known functions in both the cyst and the vegetative cell using scale qRT-PCR. Twenty-seven of 47 genes were differentially expressed in the cyst compared with the vegetative cell. In our identifications, many uncharacterized proteins were also found. These results will help reveal the molecular mechanism for the formation of cyst in ciliates.

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Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

10.26434/chemrxiv.11663337.v3 ◽

2020 ◽

Author(s):

Salvador Guardiola ◽

Monica Varese ◽

Xavier Roig ◽

Jesús Garcia ◽

Ernest Giralt

Keyword(s):

Protein Interactions ◽

Cyclic Peptides ◽

General Framework ◽

Large Scale ◽

De Novo ◽

Inhibitory Effect ◽

Original Text ◽

Protein Protein Interactions ◽

Retraction Notice ◽

Pharmaceutical Properties

NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above. ------------------------------------------------------------------------ Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-i3 and PD-i6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our de novo design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.

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A Target-Based Method for Designing Heterochiral Cyclic Peptide Binders: De Novo Inhibitors of the PD-1/PD-L1 Interaction

10.26434/chemrxiv.11663337.v2 ◽

2020 ◽

Author(s):

Salvador Guardiola ◽

Monica Varese ◽

Xavier Roig ◽

Jesús Garcia ◽

Ernest Giralt

Keyword(s):

Protein Interactions ◽

Cyclic Peptides ◽

General Framework ◽

Large Scale ◽

Cyclic Peptide ◽

De Novo ◽

Inhibitory Effect ◽

Original Text ◽

Retraction Notice ◽

Pharmaceutical Properties

NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above. ------------------------------------------------------------------------ Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-i3 and PD-i6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our de novo design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.

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Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

10.26434/chemrxiv.11663337 ◽

2020 ◽

Author(s):

Salvador Guardiola ◽

Monica Varese ◽

Xavier Roig ◽

Jesús Garcia ◽

Ernest Giralt

Keyword(s):

Protein Interactions ◽

Cyclic Peptides ◽

General Framework ◽

Large Scale ◽

De Novo ◽

Inhibitory Effect ◽

Original Text ◽

Protein Protein Interactions ◽

Retraction Notice ◽

Pharmaceutical Properties

NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above. ------------------------------------------------------------------------ Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-i3 and PD-i6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our de novo design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.

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The Evolution of Life Modes in Stictidaceae, with Three Novel Taxa

Journal of Fungi ◽

10.3390/jof7020105 ◽

2021 ◽

Vol 7 (2) ◽

pp. 105

Author(s):

Vinodhini Thiyagaraja ◽

Robert Lücking ◽

Damien Ertz ◽

Samantha C. Karunarathna ◽

Dhanushka N. Wanasinghe ◽

...

Keyword(s):

New Species ◽

Large Scale ◽

Sequence Data ◽

Large Subunit ◽

Monte Carlo Sampling ◽

Small Subunit ◽

Sensu Stricto ◽

Internal Transcribed Spacers ◽

Character State ◽

Phenotypic Data

Ostropales sensu lato is a large group comprising both lichenized and non-lichenized fungi, with several lineages expressing optional lichenization where individuals of the same fungal species exhibit either saprotrophic or lichenized lifestyles depending on the substrate (bark or wood). Greatly variable phenotypic characteristics and large-scale phylogenies have led to frequent changes in the taxonomic circumscription of this order. Ostropales sensu lato is currently split into Graphidales, Gyalectales, Odontotrematales, Ostropales sensu stricto, and Thelenellales. Ostropales sensu stricto is now confined to the family Stictidaceae, which includes a large number of species that are poorly known, since they usually have small fruiting bodies that are rarely collected, and thus, their taxonomy remains partly unresolved. Here, we introduce a new genus Ostropomyces to accommodate a novel lineage related to Ostropa, which is composed of two new species, as well as a new species of Sphaeropezia, S. shangrilaensis. Maximum likelihood and Bayesian inference analyses of mitochondrial small subunit spacers (mtSSU), large subunit nuclear rDNA (LSU), and internal transcribed spacers (ITS) sequence data, together with phenotypic data documented by detailed morphological and anatomical analyses, support the taxonomic affinity of the new taxa in Stictidaceae. Ancestral character state analysis did not resolve the ancestral nutritional status of Stictidaceae with confidence using Bayes traits, but a saprotrophic ancestor was indicated as most likely in a Bayesian binary Markov Chain Monte Carlo sampling (MCMC) approach. Frequent switching in nutritional modes between lineages suggests that lifestyle transition played an important role in the evolution of this family.

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Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK

Science ◽

10.1126/science.abf2946 ◽

2021 ◽

pp. eabf2946

Author(s):

Louis du Plessis ◽

John T. McCrone ◽

Alexander E. Zarebski ◽

Verity Hill ◽

Christopher Ruis ◽

...

Keyword(s):

Large Scale ◽

Phylogenetic Analyses ◽

Transmission Dynamics ◽

Genetic Lineage ◽

Size Dependent ◽

Spatio Temporal ◽

The Uk ◽

Lineage Structure ◽

And Control ◽

Lineage Diversity

The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, while lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.

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Genetic and morphological diversity of the cosmopolitan chaetognath Pseudosagitta maxima (Conant, 1896) in the Atlantic Ocean and its relationship with the congeneric species

ICES Journal of Marine Science ◽

10.1093/icesjms/fsw255 ◽

2017 ◽

Vol 74 (7) ◽

pp. 1875-1884 ◽

Cited By ~ 2

Author(s):

Dmitry N. Kulagin ◽

Tatiana V. Neretina

Keyword(s):

Atlantic Ocean ◽

Large Scale ◽

Phylogenetic Analyses ◽

Morphological Diversity ◽

Maturity Stage ◽

Congeneric Species ◽

Morphological Examination ◽

Posterior Teeth ◽

Biogeographic Patterns ◽

True Diversity

Abstract Until recently many oceanic zooplankton species have been considered as cosmopolitan organisms. At present it became evident that some of them comprise many distinct molecular operational taxonomic units (MOTUs) that often are regarded as cryptic species. As they can significantly change our perceptions of large-scale biogeographic patterns, it is important to characterize the true diversity within common and ecologically important groups. We have analysed the molecular and morphological diversity of the cosmopolitan mesopelagic chaetognath Pseudosagitta maxima throughout the Atlantic Ocean from 60° S to 85° N and its position within the genus Pseudosagitta. Three distinct mitochondrial clades within P. maxima were revealed with phylogenetic analyses (Maximum Likelihood, Bayesian Inference) and were geographically separated. The subsequent analyses of nuclear markers (H3, ITS1) have shown that P. maxima most likely comprises two distinct MOTUs, tropical and bipolar, that also have some morphological differences. The latter MOTU consists of two genetically slightly divergent populations: southern and northern. The morphological examination allowed the determination of a character (type of hook coloration) that accurately distinguishes juveniles of the P. maxima complex from the other congeneric species. Molecular data have shown that evolutionary P. lyra and P. gazellae are more closely related to each other than to P. maxima. Number of hooks, number of anterior and posterior teeth and the arrangement of ova in the ovary were proposed to be the most useful morphological characters to distinguish between tropical and bipolar MOTUs within the P. maxima complex. The first three characters should be determined for each maturity stage separately.

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