Project description:Recent advancements in genome sequencing have facilitated accessing the natural genetic diversity of species, unveiling hidden genetic traits, clarifying gene functions, and the degree to which laboratory studies can be generalized. One notable discovery is the frequent (~20%) aneuploidy - an imbalance in chromosome copy numbers - in natural Saccharomyces cerevisiae (Sc) isolates, despite the significant fitness costs and transient nature reported for lab-engineered yeast aneuploids. To examine this discrepancy, we adapted a high-throughput proteomic platform to analyze the proteome of 800 diverse yeast isolates. Matching these proteomes to the natural isolates’ genomes, transcriptomes, as well as generating ubiquitinome and protein turnover data for selected isolates, we report that natural and lab-generated aneuploids differ specifically at the proteome. While lab-generated aneuploids attenuate specific proteins – mostly protein complex subunits – and do not alter the average gene dosage provided by chromosome duplications, in natural strains, 70% of proteins encoded on aneuploid chromosomes are attenuated, and protein levels are shifted towards the euploid state chromosome-wide. Our data links chromosome-wide dosage compensation in natural strains to i) genome-wide buffering of gene expression changes manifesting in trans on euploid chromosomes, ii) increased expression of structural components of the ubiquitin proteasome system, and iii) increased global rates of protein turnover. Our results encourage the exploitation of natural diversity of species to understand complex biological processes at the molecular level. This submission contains the raw files for the disomics lab engineered strains, the library used for the analysis and the corresponding DIA-NN report and associated files.
Project description:Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we hypothesized that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the “coenzyme” category have been examined, including a gene cluster encoding for the co-factor pyrroloquinoline quinone (PQQ). When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides a new engineering strategy for improving polyketide production and discovering new biosynthetic gene clusters.
Project description:negative data from the malaria extract run. postive done in separate job
These are fungal extracts from the natural product library R01. Previous malaria docking already done on samples.
Project description:We have conducted a genome-wide analysis of spontaneous copy number variation (CNV) in the laboratory mouse. We used high resolution microarrays to identify 38 CNVs between 14 colonies of the C57BL/6 strain spanning ~967 generations of inbreeding, and examined these loci in 12 additional strains. It is clear from our results that many CNVs arise through a highly non-random process: 18 of 38 were the product of recurrent mutation, and rates of change vary roughly four orders of magnitude across different loci. These recurrent CNVs are distributed throughout the genome, affect 43 genes, and fluctuate in copy number over mere hundreds of generations, observations that raise questions about their contribution to natural variation. Keywords: Representational oligonucleotide microarray analysis, comparative genomic hybridization, DNA copy number variation, structural variation, inbred mice, spontaneous mutation rate
Project description:We have conducted a genome-wide analysis of spontaneous copy number variation (CNV) in the laboratory mouse. We used high resolution microarrays to identify 38 CNVs between 14 colonies of the C57BL/6 strain spanning ~967 generations of inbreeding, and examined these loci in 12 additional strains. It is clear from our results that many CNVs arise through a highly non-random process: 18 of 38 were the product of recurrent mutation, and rates of change vary roughly four orders of magnitude across different loci. These recurrent CNVs are distributed throughout the genome, affect 43 genes, and fluctuate in copy number over mere hundreds of generations, observations that raise questions about their contribution to natural variation. Keywords: comparative genomic hybridization, DNA copy number variation, structural variation, inbred mice, spontaneous mutation rate