Project description:Evolutionary alterations to cis-regulatory sequences are likely to cause adaptive phenotypic complexity, through orchestrating changes in cellular proliferation, identity and communication. For non-model organisms with adaptive key-innovations, patterns of regulatory evolution have been predominantly limited to targeted sequence-based analyses. Chromatin-immunoprecipitation with high-throughput sequencing (ChIP-seq) is a technology that has only been used in genetic model systems and is a powerful experimental tool to screen for active cis-regulatory elements. Here, we show that it can also be used in ecological model systems and permits genome-wide functional exploration of cis-regulatory elements. As a proof of concept, we use ChIP-seq technology in adult fin tissue of the cichlid fish Oreochromis niloticus to map active promoter elements, as indicated by occupancy of trimethylated Histone H3 Lysine 4 (H3K4me3). The fact that cichlids are one of the most phenotypically diverse and species-rich families of vertebrates could make them a perfect model system for the further in-depth analysis of the evolution of transcriptional regulation. examination of H3K4me3 in adult fin tissue of the Nile tilapia (Oreochromis niloticus)
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.
Project description:Evolutionary alterations to cis-regulatory sequences are likely to cause adaptive phenotypic complexity, through orchestrating changes in cellular proliferation, identity and communication. For non-model organisms with adaptive key-innovations, patterns of regulatory evolution have been predominantly limited to targeted sequence-based analyses. Chromatin-immunoprecipitation with high-throughput sequencing (ChIP-seq) is a technology that has only been used in genetic model systems and is a powerful experimental tool to screen for active cis-regulatory elements. Here, we show that it can also be used in ecological model systems and permits genome-wide functional exploration of cis-regulatory elements. As a proof of concept, we use ChIP-seq technology in adult fin tissue of the cichlid fish Oreochromis niloticus to map active promoter elements, as indicated by occupancy of trimethylated Histone H3 Lysine 4 (H3K4me3). The fact that cichlids are one of the most phenotypically diverse and species-rich families of vertebrates could make them a perfect model system for the further in-depth analysis of the evolution of transcriptional regulation.
Project description:Ctenophores’ amazing capacity of regeneration has fascinated biologists for centuries. The morphological features of ctenophore regeneration have been documented, but the molecular and cellular components behind this phenomenon have remained a mystery. Here, next generation sequencing technologies and transcriptomic analysis are used to investigate the regeneration dynamics in the ctenophore Mnemiopsis leidyi. The resulting data identify multiple signaling pathways that might be involved in ctenophore regeneration. These include evolutionarily conserved pathways, such as Ca2+-dependent and MAP-kinase signaling pathways, that are up regulated during regeneration, as well as genes involved in energetics and cytoskeleton function. The data also show evidence for involvement of dozens of ctenophore specific secretory molecules, their receptors and processing components that are important signal messengers in regeneration. A unique subset of transcription factors were also found to be involved in regeneration which may be upstream regulators of those signaling pathways. In summary, our data indicate that the strategies which ctenophores employ to regenerate use a unique combination of evolutionarily conserved and ctenophore specific signaling components. These data provide novel insights into the mechanisms of regeneration in the earliest branching taxa in Metazoa.
Project description:Coleoid cephalopods (squids, cuttlefish, octopus) have the largest nervous system among invertebrates that together with many lineage-specific morphological traits enables complex behaviors. The genomic basis underlying these innovations remains unknown. Using comparative and functional genomics in the model squid Euprymna scolopes, we reveal the unique genomic, topological, and regulatory organization of cephalopod genomes. We show that cephalopod genomes have been extensively restructured compared to other animals leading to the emergence of hundreds of tightly linked and evolutionary unique gene clusters (microsyntenies). Such novel microsyntenies correspond to topological compartments with a distinct regulatory structure and contribute to complex expression patterns. In particular, we identified a set of microsyntenies associated with cephalopod innovations (MACIs) broadly enriched in cephalopod nervous system expression. We posit that the emergence of MACIs was instrumental to cephalopod nervous system evolution and propose that microsyntenic profiling will be central to understand cephalopod innovations.
Project description:The cellular and genetic mechanism underlying the human-specific features of cortex development remains unclear. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility of the developing macaque and mouse prefrontal cortex, and conducted evolutionary analyses with the published complementary human data. The cortex cell type composition shows an overall conservation across species. We found the human neural progenitors show extensive transcriptional rewiring in the growth factor and extracellular matrix pathways. Expression of the human-specific progenitor marker ITGA2 in the cortex of fetal mouse promotes progenitor proliferation and an increased upper-layer neuron proportion. We demonstrate that these transcriptional divergences are primarily driven by the activity changes of the distal regulatory elements in the genome. Markedly, the chromatin regions with human-gained accessibility enrich the human-fixed sequence changes, as well as sequence polymorphisms associated with intelligence and neuropsychiatric disorders. Our results uncover evolutionary innovations in neural progenitors and gene regulatory mechanism during primate cortex evolution.
Project description:An International Multi-Center Study to Define the Clinical Utility of MicroarrayâBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=1,152 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. 1,152 blood or bone marrow samples of acute and chronic leukemia patients were hybridized to the Roche AmpliChip Leukemia Custom Microarray
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=2,096 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. 2096 blood or bone marrow samples of acute and chronic leukemia patients were hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips.
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=1,152 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc.