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Building a eukaryotic chromosome arm by de novo design and synthesis.

ABSTRACT: The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a "one-amino-acid-one-codon" strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.

SUBMITTER: Jiang S

PROVIDER: S-EPMC10689750 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Building a eukaryotic chromosome arm by de novo design and synthesis.

Jiang Shuangying S Luo Zhouqing Z Wu Jie J Yu Kang K Zhao Shijun S Cai Zelin Z Yu Wenfei W Wang Hui H Cheng Li L Liang Zhenzhen Z Gao Hui H Monti Marco M Schindler Daniel D Huang Linsen L Zeng Cheng C Zhang Weimin W Zhou Chun C Tang Yuanwei Y Li Tianyi T Ma Yingxin Y Cai Yizhi Y Boeke Jef D JD Zhao Qiao Q Dai Junbiao J

Nature communications 20231130 1

The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial ...[more]

PMID: 38036514

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Project description:BackgroundLTR retrotransposons are a class of mobile genetic elements containing two similar long terminal repeats (LTRs). Currently, LTR retrotransposons are annotated in eukaryotic genomes mainly through the conventional homology searching approach. Hence, it is limited to annotating known elements.ResultsIn this paper, we report a de novo computational method that can identify new LTR retrotransposons without relying on a library of known elements. Specifically, our method identifies intact LTR retrotransposons by using an approximate string matching technique and protein domain analysis. In addition, it identifies partially deleted or solo LTRs using profile Hidden Markov Models (pHMMs). As a result, this method can de novo identify all types of LTR retrotransposons. We tested this method on the two pairs of eukaryotic genomes, C. elegans vs. C. briggsae and D. melanogaster vs. D. pseudoobscura. LTR retrotransposons in C. elegans and D. melanogaster have been intensively studied using conventional annotation methods. Comparing with previous work, we identified new intact LTR retroelements and new putative families, which may imply that there may still be new retroelements that are left to be discovered even in well-studied organisms. To assess the sensitivity and accuracy of our method, we compared our results with a previously published method, LTR_STRUC, which predominantly identifies full-length LTR retrotransposons. In summary, both methods identified comparable number of intact LTR retroelements. But our method can identify nearly all known elements in C. elegans, while LTR_STRUCT missed about 1/3 of them. Our method also identified more known LTR retroelements than LTR_STRUCT in the D. melanogaster genome. We also identified some LTR retroelements in the other two genomes, C. briggsae and D. pseudoobscura, which have not been completely finished. In contrast, the conventional method failed to identify those elements. Finally, the phylogenetic and chromosomal distributions of the identified elements are discussed.ConclusionWe report a novel method for de novo identification of LTR retrotransposons in eukaryotic genomes with favorable performance over the existing methods.

Dataset Information

Building a eukaryotic chromosome arm by de novo design and synthesis.

Publications

Building a eukaryotic chromosome arm by de novo design and synthesis.

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