Ontology highlight
ABSTRACT:
PROVIDER: PRJNA705792 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13848300.fastq.gz | Fastqsanger.gz | |||
| SRR13848300_1.fastq.gz | Fastqsanger.gz | |||
| SRR13848300_2.fastq.gz | Fastqsanger.gz | |||
| SRR13848301.fastq.gz | Fastqsanger.gz | |||
| SRR13848301_1.fastq.gz | Fastqsanger.gz |
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Project description:Molecular phylogenomics investigates evolutionary relationships based on genomic data. However, despite genomic sequence conservation, changes in protein interactions can occur relatively rapidly and may cause strong functional diversification. To investigate such functional evolution, we here combine phylogenomics with interaction proteomics. We develop this concept by investigating the molecular evolution of the shelterin complex, which protects telomeres, across 16 vertebrate species from zebrafish to humans covering 450 million years of evolution. Our phylointeractomics screen discovers previously unknown telomere-associated proteins and reveals how homologous proteins undergo functional evolution. For instance, we show that TERF1 evolved as a telomere-binding protein in the common stem lineage of marsupial and placental mammals. Phylointeractomics is a versatile and scalable approach to investigate evolutionary changes in protein function and thus can provide experimental evidence for phylogenomic relationships.
2017-02-15 | PXD005517 | Pride
Project description:Polyploidy or whole genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R Hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and the 2R event occurred in the gnathostome stem-lineage, maximally in the late Cambrian-earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced at least an additional, independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only after the 2R event, questioning the general expectation that WGDs lead to leaps of bodyplan complexity.
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Project description:Traditionally, the study of evolution has focused on heritable variation, because selection on non-heritable phenotypic variation was deemed non-important for its inability to cause evolutionary responses such as diversification of lineages. Recently however, it has been suggested that also environmentally induced phenotypic variation such as phenotypic plasticity can play an important role in adaptive responses resulting in diversification. The purpose of this study is to investigate the importance of phenotypic plasticity for the diversification of lineages, using life history, morphological traits, and genomic profiling during post embryonic development in plastic and non-plastic genotypes of the common frog Rana temporaria. Six animals each originating from four different islands were reared in either constant or reduced water conditions and hepatic mRNA levels of Gosner stage 37 animals evaluated by MAGEX DNA array analysis.
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Project description:Small molecule-triggered protein degradation tags (degrons) are powerful tools for biology, biotechnology, and therapeutics development. Commonly used degrons, however, are large protein domains (typically >100 amino acids) that cannot be easily or cleanly installed in endogenous protein-coding genes in most cell types. Although some zinc-finger (ZF) degrons are theoretically small enough for facile endogenous tagging, all are triggered by small molecules with substantial off-target effects, precluding their use as highly specific modulators of endogenous protein levels. We developed a phage-assisted continuous evolution platform for molecular glues (MG-PACE) and applied it to evolve ZF degrons that engage cereblon (CRBN) only in the presence of orthogonal thalidomide derivatives. MG-PACE evolved a 36-amino acid ZF degron (SD40) that binds CRBN with high affinity in the presence of PT-179, a thalidomide derivative with no detected neosubstrate activity. The evolved degron is small enough to be efficiently inserted into targeted genomic sites in human cells using prime editing. Human proteins tagged with the evolved degron are rapidly and potently degraded by the otherwise-inert PT-179. To overcome the inactivity of IMiD-based degrons in rodents, we separately used MG-PACE to evolve ZF degrons that engage mouse CRBN, enabling induced target protein degradation in mouse cells. High-resolution cryo-electron microscopy structures of SD40 in complex with CRBN/DDB1 bound to PT-179 or pomalidomide reveal mechanistic insights into the evolution and molecular basis of SD40’s activity and specificity. Collectively, our efforts establish a system for the rapid evolution of molecular glue complexes with novel specificities and compact ZF tags that overcome shortcomings associated with existing degrons.
2024-08-09 | PXD047665 | Pride
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2024-08-09 | PXD047593 | Pride
Project description:Small molecule-triggered protein degradation tags (degrons) are powerful tools for biology, biotechnology, and therapeutics development. Commonly used degrons, however, are large protein domains (typically >100 amino acids) that cannot be easily or cleanly installed in endogenous protein-coding genes in most cell types. Although some zinc-finger (ZF) degrons are theoretically small enough for facile endogenous tagging, all are triggered by small molecules with substantial off-target effects, precluding their use as highly specific modulators of endogenous protein levels. We developed a phage-assisted continuous evolution platform for molecular glues (MG-PACE) and applied it to evolve ZF degrons that engage cereblon (CRBN) only in the presence of orthogonal thalidomide derivatives. MG-PACE evolved a 36-amino acid ZF degron (SD40) that binds CRBN with high affinity in the presence of PT-179, a thalidomide derivative with no detected neosubstrate activity. The evolved degron is small enough to be efficiently inserted into targeted genomic sites in human cells using prime editing. Human proteins tagged with the evolved degron are rapidly and potently degraded by the otherwise-inert PT-179. To overcome the inactivity of IMiD-based degrons in rodents, we separately used MG-PACE to evolve ZF degrons that engage mouse CRBN, enabling induced target protein degradation in mouse cells. High-resolution cryo-electron microscopy structures of SD40 in complex with CRBN/DDB1 bound to PT-179 or pomalidomide reveal mechanistic insights into the evolution and molecular basis of SD40’s activity and specificity. Collectively, our efforts establish a system for the rapid evolution of molecular glue complexes with novel specificities and compact ZF tags that overcome shortcomings associated with existing degrons.
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Project description:Traditionally, the study of evolution has focused on heritable variation, because selection on non-heritable phenotypic variation was deemed non-important for its inability to cause evolutionary responses such as diversification of lineages. Recently however, it has been suggested that also environmentally induced phenotypic variation such as phenotypic plasticity can play an important role in adaptive responses resulting in diversification. The purpose of this study is to investigate the importance of phenotypic plasticity for the diversification of lineages, using life history, morphological traits, and genomic profiling during post embryonic development in plastic and non-plastic genotypes of the common frog Rana temporaria.
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