Widespread transcriptional scanning in the testis modulates gene evolution rates
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ABSTRACT:
PROVIDER: PRJNA515940 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8460430_1.fastq.gz | Fastqsanger.gz | |||
| SRR8460430_2.fastq.gz | Fastqsanger.gz | |||
| SRR8460431_1.fastq.gz | Fastqsanger.gz | |||
| SRR8460431_2.fastq.gz | Fastqsanger.gz | |||
| SRR8460426_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Our detailed transcriptomic map of human and mouse spermatogenesis provides evidence that this widespread transcription serves to maintain DNA sequence integrity in the male germline by correcting DNA damage through “transcriptional scanning”. Supporting this model, we find that genes expressed during spermatogenesis display lower mutation rates on the transcribed strand and have low diversity in the population, while unexpressed genes evolve faster and are enriched for sensory and immune-defense functions. Thus, we propose that transcriptional scanning modulates mutation rates in a gene-specific manner, maintaining germline DNA sequence integrity for the bulk of genes but allowing for fast evolution in a specific subset.
2020-01-23 | GSE125372 | GEO
Project description:The testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Our single-cell transcriptomic data of human and mouse spermatogenesis provide evidence that this widespread transcription maintains DNA sequence integrity in the male germline by correcting DNA damage through a mechanism we term transcriptional scanning. We find that genes expressed during spermatogenesis display lower mutation rates on the transcribed strand and have low diversity in the population. Moreover, this effect is fine-tuned by the level of gene expression during spermatogenesis. The unexpressed genes, which in our model do not benefit from transcriptional scanning, diverge faster over evolutionary timescales and are enriched for sensory and immune-defense functions. Collectively, we propose that transcriptional scanning shapes germline mutation signatures and modulates mutation rates in a gene-specific manner, maintaining DNA sequence integrity for the bulk of genes but allowing for faster evolution in a specific subset.
| S-EPMC7891839 | biostudies-literature
Project description:Gene expression levels are determined by the balance between rates of mRNA transcription and decay, and genetic variation in either of these processes can result in heritable differences in transcript abundance. Although the genetics of gene expression has been the subject of intense interest, the contribution of heritable variation in mRNA decay rates to gene expression variation has received far less attention. To this end, we developed a novel statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. In total, we estimate that 31% of genes exhibit allelic differences in mRNA decay rate, of which 350 can be identified at a false discovery rate of 10%. Genes with significant allele-specific differences in mRNA decay rate have higher levels of polymorphism compared to other genes, with all gene regions contributing to allelic differences in mRNA decay rate. Strikingly, we find widespread evidence for compensatory evolution, such that variants influencing transcriptional initiation and decay having opposite effects, suggesting steady-state gene expression levels are subject to pervasive stabilizing selection. Our results demonstrate that heritable differences in mRNA decay rates are widespread, and are an important target for natural selection to maintain or fine-tune steady-state gene expression levels.
2014-09-16 | GSE60617 | GEO
Project description:Translation is initiated by binding of the eIF4F complex to the 5' cap of the mRNA, which is followed by scanning of the initiation codon by scanning ribosomes. Here we demonstrate that the ASC-1 complex (ASCC), which was previously shown to promote the dissociation of colliding 80S ribosomes, associates with the scanning ribosomes to regulate translation initiation. Sel-TCP-seq analysis revealed that ASCC3, a subunit of ASCC with a helicase domain, localizes predominantly to the 5' untranslated region of mRNAs. Knockdown of ASCC3 resulted in reduced translation efficiency associated with reduced 43S preinitiation complex (PIC) loading and a reduced speed of scanning ribosomes. In addition, depletion of the ubiquitin ligase ZNF598, a sensor of collided 80S ribosomes, also reduces the PIC loading and speed of scanning ribosomes. Our results have thus revealed that ASCC is required not only for dissociation of colliding 80S ribosomes, but also for efficient translation initiation by scanning ribosomes.
2023-03-31 | GSE186502 | GEO
Project description:Biochar-different rates Raw sequence reads
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Project description:Gene expression levels are determined by the balance between rates of mRNA transcription and decay, and genetic variation in either of these processes can result in heritable differences in transcript abundance. Although the genetics of gene expression has been the subject of intense interest, the contribution of heritable variation in mRNA decay rates to gene expression variation has received far less attention. To this end, we developed a novel statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. In total, we estimate that 31% of genes exhibit allelic differences in mRNA decay rate, of which 350 can be identified at a false discovery rate of 10%. Genes with significant allele-specific differences in mRNA decay rate have higher levels of polymorphism compared to other genes, with all gene regions contributing to allelic differences in mRNA decay rate. Strikingly, we find widespread evidence for compensatory evolution, such that variants influencing transcriptional initiation and decay having opposite effects, suggesting steady-state gene expression levels are subject to pervasive stabilizing selection. Our results demonstrate that heritable differences in mRNA decay rates are widespread, and are an important target for natural selection to maintain or fine-tune steady-state gene expression levels. We measured rates of allele-specific mRNA decay (ASD) in a diploid yeast produced by mating two genetically diverse haploid Saccharomyces cerevisiae strains: the laboratory strain BY4716 (BY), which is isogenic to the reference sequence strain S288C, and the wild Californian vineyard strain RM11-1a (RM). Briefly, we introduced rpb1-1, a temperature sensitive mutation in an RNA polymerase II subunit, to each of the haploid yeast strains, mated the strains, and grew the resulting hybrid diploid to mid-log phase at 24 M-BM-0C, before rapidly shifting the culture to 37 M-BM-0C to inhibit transcription. RNA-seq was performed on culture samples taken at 0, 6, 12, 18, 24, and 42 minutes subsequent to the temperature shift. To identify ASD, we used transcribed polymorphisms to distinguish between parental transcripts, and compared the relative levels of transcript abundance over the time course. Note, this experimental design internally controls for trans-acting regulatory variation as well as environmental factors. Under the null hypothesis of no ASD, the proportion of reads from the BY transcript (p_BY = N_BY / (N_BY + N_RM)) observed over the time course remains unchanged. However, genes with ASD will exhibit an increasing or decreasing proportion of BY reads as a function of time. In total, we measured ASD from three independent biological replicates.
2014-09-16 | E-GEOD-60617 | biostudies-arrayexpress
Project description:A scanning quadrupole data independent acquisition (DIA) method is described and characterised for the qualitative and quantitative label free proteomic analysis of complex biological samples. The principle of the scanning quadrupole DIA is discussed and the effect of the optimization of analytical instrument characteristics, such as acquisition speed, sample complexity, and scan/integration time in relation to sample complexity for a number of different model proteomes of various complexity and dynamic range, including plasma, human cell lines, and bacteria samples, discussed. In addition, its technological merits from an acquisition neutral perspective are reviewed. The qualitative and semi-quantitative performance of the method is illustrated and contrasted for the analysis of a well-characterised human cell line sample using untargeted and targeted search strategies. The application of the method is demonstrated for the analysis of the calcineurin-dependent proteome of drug treated Aspergillus fumigatus. The design of these experiments afforded assessment of the precision and accuracy of scanning quadrupole data independent acquisition (DIA) method as will be demonstrated by peptide and protein centric analysis of the study pool QC samples of the study. Moreover, novel and specific interactors in response to drug treatment that are indicative of the role of calcineurin role in regulating these effectors have been identified.
2017-09-14 | PXD005869 | Pride
Project description:Temperature-dependence of spontaneous mutation rates
| PRJEB44550 | ENA