Spontaneous-signature-mutation
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB44312 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR5717060_1.fastq.gz | Fastqsanger.gz | |||
| ERR5717060_2.fastq.gz | Fastqsanger.gz | |||
| ERR5717061_1.fastq.gz | Fastqsanger.gz | |||
| ERR5717061_2.fastq.gz | Fastqsanger.gz | |||
| ERR5717062_1.fastq.gz | Fastqsanger.gz |
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Project description:Experiment to estimate mutatational variance of gene expression in Drosophila melanogaster at two times in development using 12 mutation accumulation lines. Keywords = evolution Keywords = quantitative genetics Keywords = Drosophila Keywords = mutation Keywords: other
2005-09-04 | GSE2126 | GEO
Project description:Numerous single gene mutations identified in humans and mice result in nail deformities with many similarities between the species. A spontaneous, autosomal, recessive mutation called witch nails whnl is described here where the distal nail matrix and nail bed undergo degenerative changes resulting in formation of an abnormal nail plate causing mice to develop long, curved nails. This mutation arose spontaneously in a colony of MRL MpJ-Faslpr J at The Jackson Laboratory. Homozygous mutant mice are recognizable by 8 weeks of age by their long, curved nails. The whnl mutation, mapped on Chromosome 15, is due to a 7-bp insertion identified in the 3 region of exon 9 in the Krt90 gene formerly Riken cDNA 4732456N10Rik, and is predicted to result in a frameshift that changes serine 476 to arginine and subsequently introduces 36 novel amino acids into the protein before a premature stop codon p. Ser476ArgfsTer36. By immunohistochemistry the normal KRT90 protein is expressed in the nail matrix and nail bed in control mice where lesions are located in mutant mice. Immunoreactivity toward equine KRT124, the ortholog of mouse KRT90, is restricted to the nail bed of the hoof and the mouse nail unit. Equine laminitis lesions are similar to those observed in this mutant mouse suggesting that the latter may be a useful model for this horse disease. This first spontaneous mouse mutation affecting the novel Krt90 gene provides new insight into the normal regulation of the molecular pathways of nail development.
2022-07-05 | MSV000089811 | MassIVE
Project description:The spontaneous mutation rate is a crucial parameter in molecular evolution which is maintained very low. To better characterize how proofreading activity of the DNA polymerase and Mismatch repair (MMR) which are ubiquitous in all kingdoms of life shape a mutational landscape we built B. subtilis 168-derived strains allowing conditional inactivation of either one or both of these two error reparation mechanisms. In practice, we used an IPTG-inducible promoter to control the expression of mutant alleles selected for their ability to displace by competition their functional counterparts. The first allele, denoted here mutL*, has a mutation in the ATP hydrolysis active site of MutL. The second allele, denoted here polC* encodes an exonuclease-deficient variant of PolC. Fluctuation tests and Mutation Accumulation experiments confirmed extremely high mutation rates, upon IPTG-induction, in the strain that combine these two deficient alleles in a synthetic operon (mutL*//polC*). The purpose of this transcritomic study was to better characterize this inducible system. Analysis of the data did not reveal specific transcriptional responses of the bacterium to IPTG addition and extreme mutations rates.
2024-03-25 | GSE239804 | GEO
Project description:Experiment to estimate mutatational variance of gene expression in Drosophila melanogaster at two times in development using 12 mutation accumulation lines. Keywords = evolution Keywords = quantitative genetics Keywords = Drosophila Keywords = mutation Each of 12 lines measured 8 times in each of two stages. For each stage, the design has two hexagons with 6 interior connections (=hybridizations) (all except opposite nodes). Each line in one hexagon is connected to one line in the other hexagon and that line's opposite. Each line is also connected to itself twice in the other stage. Dyes are balanced.
2010-06-09 | E-GEOD-2126 | biostudies-arrayexpress
Project description:Initiation and progression of cancers reflect the underlying process of somatic evolution, which follows a Darwinian logic, i.e., diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination – a key diversification mechanism throughout all strata of life. Based on observations of spontaneous fusions involving cancer cells, reported genetic instability of polypoid cells, and precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions could serve as a source of parasexual recombination in cancer cell populations. Using differentially labelled tumor cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modeling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumor cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape, relative to strictly asexual populations, which may substantially accelerate a tumor’s ability to adapt to new selective pressures.
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Project description:Temperature-dependence of spontaneous mutation rates
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Project description:Initiation and progression of cancers reflect the underlying process of somatic evolution, which follows a Darwinian logic, i.e., diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination – a key diversification mechanism throughout all strata of life. Based on observations of spontaneous fusions involving cancer cells, reported genetic instability of polypoid cells, and precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions could serve as a source of parasexual recombination in cancer cell populations. Using differentially labelled tumor cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modeling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumor cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape, relative to strictly asexual populations, which may substantially accelerate a tumor’s ability to adapt to new selective pressures.
2020-10-21 | GSE159680 | GEO
Project description:Initiation and progression of cancers reflect the underlying process of somatic evolution, which follows a Darwinian logic, i.e., diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination – a key diversification mechanism throughout all strata of life. Based on observations of spontaneous fusions involving cancer cells, reported genetic instability of polypoid cells, and precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions could serve as a source of parasexual recombination in cancer cell populations. Using differentially labelled tumor cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modeling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumor cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape, relative to strictly asexual populations, which may substantially accelerate a tumor’s ability to adapt to new selective pressures.
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Project description:Repetitive sequences are hotspots of evolution at multiple levels. However, due to technical difficulties involved in their assembly and analysis, the role of repeats in tumor evolution is poorly understood. We developed a rigorous motif-based methodology to quantify variations in the repeat content of proteomes and genomes, directly from proteomic and genomic raw sequence data, and applied it to analyze a wide range of tumors and normal tissues. We identify high similarity between the repeat-instability in tumors and their patient-matched normal tissues, but also tumor-specific signatures, both in protein expression and in the genome, that strongly correlate with cancer progression and robustly predict the tumorigenic state. In a patient, the hierarchy of genomic repeat instability signatures accurately reconstructs tumor evolution, with primary tumors differentiated from metastases. We find an inverse relationship between repeat-instability and point mutation load, within and across patients, and independently of other somatic aberrations. Thus, repeat-instability is a distinct, transient and compensatory adaptive mechanism in tumor evolution.
2020-06-02 | PXD012574 | Pride
Project description:Somatic mutations arise during the life history of a cell. Mutations occurring in cancer driver genes may ultimately lead to the development of clinically detectable disease. Nascent cancer lineages continue to acquire somatic mutations throughout the neoplastic process and during cancer evolution. Extrinsic and endogenous mutagenic factors contribute to the accumulation of these somatic mutations. Understanding the underlying causes of mutations is critical for developing potential preventions and tailoring the clinical treatments. Earlier studies have revealed that DNA replication timing and chromatin modifications are associated with variations in mutational density. In order to understand the interplay between spatial genome organization and individual mutational processes, we report here a study of more than 3000 whole genome datasets from 50 different cancer studies. Our analyses revealed that different mutational processes lead to distinct somatic mutation distributions between chromatin folding domains. APOBEC- or MSI-related mutations are enriched in transcriptionally-active domains while mutations occurring due to tobacco-smoke and ultraviolet (UV) light exposure or a gastric flux-related mutational signature (signature 17) enrich predominantly in transcriptionally-inactive domains. Active mutational processes dictate the mutation distributions in cancer genomes, therefore mutational distributions could shift during cancer evolution upon mutational processes switch. Moreover, a dramatic instance of extreme chromatin structure in humans, that of the unique folding pattern of the inactive X-chromosome leads to distinct somatic mutation distribution on X chromosome in females compared to males in various cancer types. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation rate variations observed in human cancer.
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