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[学术文献 ] Engineered extrachromosomal oncogene amplifications promote tumorigenesis 进入全文
nature
Focal gene amplifications are among the most common cancer-associated mutations1 but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs)2 in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures. We also apply this approach to generate mice harbouring Cre-inducible Myc- and Mdm2-containing ecDNAs analogous to those occurring in human cancers. We show that the engineered ecDNAs spontaneously accumulate in primary cells derived from these animals, promoting their proliferation, immortalization and transformation. Finally, we demonstrate the ability of Mdm2-containing ecDNAs to promote tumour formation in an autochthonous mouse model of hepatocellular carcinoma. These findings offer insights into the role of ecDNA-mediated gene amplifications in tumorigenesis. We anticipate that this approach will be valuable for investigating further unresolved aspects of ecDNA biology and for developing new preclinical immunocompetent mouse models of human cancers harbouring specific focal gene amplifications.
[学术文献 ] The Quest for the Sli Locus 进入全文
Potato Research
Genetic gain in potato breeding is limited by the heterozygous tetraploid genome of cultivated potato. Recent efforts to breed potato at the diploid level promise to improve genetic gain and allow more straightforward genetics and introgression breeding. Diploid F1 hybrid potato breeding relies on the ability to create diploid inbred lines via repeated self-fertilization. However, self-fertilization of diploid potato is hampered by a gametophytic self-incompatibility system encoded by the S-locus that prevents fertilization by self-pollen. Nonetheless, self-compatible diploid potato genotypes exist and have been used to create inbred lines. The S-locus inhibitor (Sli) gene is a dominant gene that provides strong self-compatibility in diploid potato and was previously mapped to Chromosome 12. While the Sli gene has already been identified and characterized, the most tedious challenge was to develop the optimal phenotyping methods and genetic populations preceding the cloning of this gene. To this end, we developed an effective phenotyping protocol to identify suitable parents and create diploid populations segregating for Sli. We show that an accurate phenotyping method is crucial to discriminate between confounding fertility factors and self-compatibility. In addition, we found that the Sli locus shows extreme segregation distortion on Chromosome 12. Finally, we used these insights to develop three F1 populations that segregate for Sli, which we later used for the identification of the Sli gene.
[学术文献 ] Identification, Elucidation and Deployment of a Cytoplasmic Male Sterility System for Hybrid Potato 进入全文
Biology
Conventional potato breeding has produced only limited genetic gain due to the polyploid nature of the crop. In recent years, hybrid potato breeding at the diploid level has been developed to overcome this limited genetic gain. In diploid potato breeding, homozygous inbred lines are developed by self-fertilization, enabling incremental improvements of the material in each generation. This type of breeding requires self-fertility, which makes hybridization of inbred lines labor-cumbersome and results in hybrids that produce many undesirable berries in the field. In many crop species, cytoplasmic male sterility is used to produce maternal inbred lines that are male sterile. In this study, we explore the antherless cytoplasmic male sterility system in potato. We identify a recessive locus that is required for sterility and we show that this trait is expressed in Phureja cytoplasm but not in Andigena or Tuberosum cytoplasm. We implemented this system in hybrid seed production and show that the resulting hybrids set far fewer berries in the field than male fertile controls.
[学术文献 ] A cellulose synthase–like protein governs the biosynthesis of Solanum alkaloids 进入全文
SCIENCE / PLANT SCIENCE
Steroid-based natural products produced in Solanum species act as chemical defense molecules against pests and pathogens, and some also have antinutritional properties for humans. Two groups now report the identification of a cellulose synthase–like protein named GAME15 that directs the biosynthesis of these secondary metabolites. Jozwiak et al. found that GAME15 functions both as a cholesterol glucuronosyltransferase and as a scaffolding protein in a metabolon that controls cholesterol and steroidal glycoalkaloid intermediates. Boccia et al. identified the same protein and showed that deletion of the corresponding gene in Solanum nigrum produced plants lacking both steroidal alkaloids and saponins. Identification of GAME15 will pave the way to engineering the production of chemical defense molecules in heterologous plant hosts, and may aid our understanding of the balance between chemical defense and self-toxicity.
[学术文献 ] A high-quality chromosome-level genome assembly of the traditional Chinese medicinal herb Zanthoxylum nitidum 进入全文
Scientific Data
Dried roots of Zanthoxylum nitidum (2n=2x=70, family Rutaceae) was referred as “Liang-Mian-Zhen” in Chinese, acting as a valuable species due to its notable pharmacological activities. Herein, we combined PacBio HiFi data together with Hi-C mapping technology to construct a chromosome-scale reference genome assembly for Z. nitidum. The assembly reached a length of 2.24 Gb, successfully anchoring 99.31% of sequences onto 35 pseudo-chromosomes. Among these, 26 chromosomes achieved telomere-to-telomere assembly, and 11 chromosomes were gap-free. The contigs N50 and scaffolds N50 reached 57.61 Mb and 78.00 Mb, respectively. Transposable elements comprised 81.44% of the Z. nitidum genome, and over 78% of them were long-terminal repeat retrotransposon elements. Furthermore, 32,737 protein-coding genes were identified and 99.38% of all were functionally annotated. The completeness of the genome assembly and final gene sets reached 97.83% and 96.47% based on Benchmarking Universal Single-Copy Orthologs (BUSCO), respectively. Taken together, our results provided a high-quality chromosome-level assembly of Z. nitidum genome and will be a valuable resource that will facilitate breeding varieties with higher alkaloids content.
[学术文献 ] Past innovations and future possibilities in plantchromosome engineering 进入全文
Plant Biotechnology Journal
Plant chromosome engineering has emerged as a pivotal tool in modern plant breeding,facilitating the transfer of desirable traits through the incorporation of alien chromosome fragments into plants. Here, we provide a comprehensive overview of the past achievements,current methodologies and future prospects of plant chromosome engineering. We begin by examining the successful integration of specific examples such as the incorporation of rye chromosome segments (e.g. the 1BL/1RS translocation), Dasypyrum villosum segments (e.g. the 6VS segment for powdery mildew resistance), Thinopyrum intermedium segments (e.g. rust resistance genes) and Thinopyrum elongatum segments (e.g. Fusarium head blight resistance genes). In addition to trait transfer, advancements in plant centromere engineering have opened new possibilities for chromosomal manipulation. This includes the development of plant minichromosomes via centromere-mediated techniques, the generation of haploids through CENH3 gene editing, and the induction of aneuploidy using KaryoCreate. The advent of CRISPR/Cas technology has further revolutionized chromosome engineering, enabling large-scale chromosomal rearrangements, such as inversions and translocations, as well as enabling targeted insertion of large DNA fragments and increasing genetic recombination frequency. These advancements have significantly expanded the toolkit for genetic improvement in plants, opening new horizons for the future of plant breeding.
