Project description:About 430 million years ago spiders and scorpions evolved from a common ancestor that had experienced a whole genome duplication (WGD) The genetic remnants of this WGD event (genes called ohnologs) can still be found in the genome of the approximately 45,000 species of these animals alive today and these ohnologs may have contributed to their adaptation and diversification. Interestingly, the WGD in arachnids like scorpions and spiders was contemporary with independent WGDs in vertebrates. This presents an opportunity to compare these events to determine if there are general principals underlying the outcomes of WGDs and their contribution to animal diversification. Therefore, the aims of this project are to identify arachnid ohnologs, explore how they have contributed to the evolutionary success of these animals, and compare the outcomes of this event to WGD in vertebrates. This includes sequencing new genomes and transcriptomes of species occupying key phylogenetic positions.
Project description:<p>We use untargeted metabolomics to investigate the immediate phytochemical effects of autopolyploidy on our model system, the greater duckweed <em>Spirodela polyrhiza</em>, a small aquatic macrophyte from the family Lemnaceae. We compare metabolite abundances in four genetically distinct diploid-autotetraploid pairs to address potential implications for establishment and combine traditional dry mass normalization with nuclear density information to investigate the link with gene dosage. We found that autopolyploidy increases metabolite levels per cell, although there is considerable variation in the response of individual metabolites. However, the impact on metabolite level per biomass is limited because the increased cell size reduces metabolite concentration per cell. Nevertheless, whole genome duplication (WGD) still exerts a discernible quantitative and qualitative influence on the phytochemical composition of our strains, each with potential ecological implications. While some metabolite levels are consistently higher in all tetraploids, many effects are restricted to a single strain, reflecting the importance of genetic background.</p>
Project description:Impaired control of the G1/S checkpoint allows initiation of DNA replication under non-permissive conditions. Unscheduled S-phase entry is associated with DNA replication stress, demanding for other checkpoints or cellular pathways to maintain proliferation. Here, we uncovered a requirement for ADARp150 to sustain proliferation of G1/S-checkpoint-defective cells under growth-restricting conditions. Besides its well-established mRNA editing function in inversely oriented short interspersed nuclear elements (SINEs), we found ADARp150 to exert a critical function in mitosis. ADARp150 depletion resulted in tetraploidization, impeding cell proliferation in mitogen-deprived conditions. Mechanistically we show that ADAR1 depletion induced aberrant expression of Cyclin B3, which was causative for mitotic failure and whole-genome duplication. Finally, we find that also in vivo ADAR1-depletion-provoked tetraploidization hampers tumor outgrowth.
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.
Project description:Potocki-Shaffer syndrome (PSS) is a rare contiguous gene deletion syndrome marked by haploinsufficiency of genes in chromosomal region 11p11.2p12. Approximately 50 cases of PSS have been reported; however, a syndrome with a PSS-like clinical phenotype caused by 11p11.12p12 duplication has not yet been reported. We first report the 11p11.12p12 duplication in a family with intellectual disability and craniofacial anomalies. 11p11.12p12 duplication syndrome was identified by karyotype analysis. Next-generation sequencing (NGS) analysis clarified the location of the chromosomal variations, which was confirmed by chromosome microarray analysis (CMA). Whole-exome sequencing (WES) was performed to exclude single nucleotide variations (SNVs). The raw data of NGS analysis and WES have been submitted to SRA, the accession number is PRJNA713823.