All Publications


  • CGC1, a new reference genome for Caenorhabditis elegans. bioRxiv : the preprint server for biology Ichikawa, K., Shoura, M. J., Artiles, K. L., Jeong, D. E., Owa, C., Kobayashi, H., Suzuki, Y., Kanamori, M., Toyoshima, Y., Iino, Y., Rougvie, A. E., Wahba, L., Fire, A. Z., Schwarz, E. M., Morishita, S. 2024

    Abstract

    The original 100.3 Mb reference genome for Caenorhabditis elegans, generated from the wild-type laboratory strain N2, has been crucial for analysis of C. elegans since 1998 and has been considered complete since 2005. Unexpectedly, this long-standing reference was shown to be incomplete in 2019 by a genome assembly from the N2-derived strain VC2010. Moreover, genetically divergent versions of N2 have arisen over decades of research and hindered reproducibility of C. elegans genetics and genomics. Here we provide a 106.4 Mb gap-free, telomere-to-telomere genome assembly of C. elegans, generated from CGC1, an isogenic derivative of the N2 strain. We used improved long-read sequencing and manual assembly of 43 recalcitrant genomic regions to overcome deficiencies of prior N2 and VC2010 assemblies, and to assemble tandem repeat loci including a 772-kb sequence for the 45S rRNA genes. While many differences from earlier assemblies came from repeat regions, unique additions to the genome were also found. Of 19,972 protein-coding genes in the N2 assembly, 19,790 (99.1%) encode products that are unchanged in the CGC1 assembly. The CGC1 assembly also may encode 183 new protein-coding and 163 new ncRNA genes. CGC1 thus provides both a completely defined reference genome and corresponding isogenic wild-type strain for C. elegans, allowing unique opportunities for model and systems biology.

    View details for DOI 10.1101/2024.12.04.626850

    View details for PubMedID 39677790

    View details for PubMedCentralID PMC11643116

  • DNA polymerase diversity reveals multiple incursions of Polintons during nematode evolution. Molecular biology and evolution Jeong, D. E., Sundrani, S., Hall, R. N., Krupovic, M., Koonin, E. V., Fire, A. Z. 2023

    Abstract

    Polintons are dsDNA, virus-like self-synthesizing transposons widely found in eukaryotic genomes. Recent metagenomic discoveries of Polinton-like viruses are consistent with the hypothesis that Polintons invade eukaryotic host genomes through infectious viral particles. Nematode genomes contain multiple copies of Polintons and provide an opportunity to explore the natural distribution and evolution of Polintons during this process. We performed an extensive search of Polintons across nematode genomes, identifying multiple full-length Polinton copies in several species. We provide evidence of both ancient Polinton integrations and recent mobility in strains of the same nematode species. In addition to the major nematode Polinton family, we identified a group of Polintons that are overall closely related to the major family, but encode a distinct protein-primed B family DNA polymerase (pPolB) that is related to homologs from a different group of Polintons present outside of the Nematoda. Phylogenetic analyses on the pPolBs support the evolutionary scenarios in which these extrinsic pPolBs that seem to derive from Polinton families present in oomycetes and molluscs replaced the canonical pPolB in subsets of Polintons found in terrestrial and marine nematodes, respectively, suggesting inter-phylum horizontal gene transfers. The pPolBs of the terrestrial nematode and oomycete Polintons share a unique feature, an insertion of a HNH nuclease domain, whereas the pPolBs in the marine nematode Polintons share an insertion of a VSR nuclease domain with marine mollusc pPolBs. We hypothesize that horizontal gene transfer occurs among Polintons from widely different but cohabiting hosts.

    View details for DOI 10.1093/molbev/msad274

    View details for PubMedID 38069639

  • Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop JOURNAL OF CELL BIOLOGY Lee, Y., Jung, Y., Jeong, D., Hwang, W., Ham, S., Park, H. H., Kwon, S., Ashraf, J. M., Murphy, C. T., Lee, S. 2021; 220 (5)

    Abstract

    A hallmark of aging is immunosenescence, a decline in immune functions, which appeared to be inevitable in living organisms, including Caenorhabditis elegans. Here, we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically enhances immunocompetence in old age in C. elegans. We demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. In contrast, p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunity, is only partially required for this rejuvenated immunity. The up-regulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip-10/bZIP transcription factor, which in turn down-regulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS prevents immune aging via the up-regulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a feedforward mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies against immune aging in humans.

    View details for DOI 10.1083/jcb.202006174

    View details for Web of Science ID 000626391900001

    View details for PubMedID 33666644

    View details for PubMedCentralID PMC7941181

  • An Extensive Meta-Metagenomic Search Identifies SARS-CoV-2-Homologous Sequences in Pangolin Lung Viromes. mSphere Wahba, L., Jain, N., Fire, A. Z., Shoura, M. J., Artiles, K. L., McCoy, M. J., Jeong, D. 2020; 5 (3)

    Abstract

    In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic data sets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic data set can be readily queried using web-based tools, meta-searches through all such data sets are less accessible. In this brief communication, we demonstrate such a meta-metagenomic approach, examining close matches to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all high-throughput sequencing data sets in the NCBI Sequence Read Archive accessible with the "virome" keyword. In addition to the homology to bat coronaviruses observed in descriptions of the SARS-CoV-2 sequence (F. Wu, S. Zhao, B. Yu, Y. M. Chen, et al., Nature 579:265-269, 2020, https://doi.org/10.1038/s41586-020-2008-3; P. Zhou, X. L. Yang, X. G. Wang, B. Hu, et al., Nature 579:270-273, 2020, https://doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in metavirome data sets generated from the lungs of deceased pangolins reported by Liu et al. (P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979). While analysis of these reads indicates the presence of a similar viral sequence in pangolin lung, the similarity is not sufficient to either confirm or rule out a role for pangolins as an intermediate host in the recent emergence of SARS-CoV-2. In addition to the implications for SARS-CoV-2 emergence, this study illustrates the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences.IMPORTANCE Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.

    View details for DOI 10.1128/mSphere.00160-20

    View details for PubMedID 32376697

  • Inhibition of the oligosaccharyl transferase in Caenorhabditis elegans that compromises ER proteostasis suppresses p38-dependent protection against pathogenic bacteria PLOS GENETICS Jeong, D., Lee, Y., Ham, S., Lee, D., Kwon, S., Park, H. H., Hwang, S., Yoo, J., Roh, T., Lee, S. V. 2020; 16 (3)
  • Genetic inhibition of an ATP synthase subunit extends lifespan in C-elegans SCIENTIFIC REPORTS Xu, C., Hwang, W., Jeong, D., Ryu, Y., Ha, C., Lee, S. V., Liu, L., He, Z. 2018; 8: 14836

    Abstract

    Mild inhibition of mitochondrial respiration leads to longevity. Disruption of mitochondrial respiratory components extends lifespan in Caenorhabditis elegans, but the effects appear to be complex and the underlying mechanism for lifespan regulation by mitochondrial respiratory genes is still not fully understood. Here, we investigated the role of Y82E9BR.3, a worm homolog of the ATP synthase subunit C, in modulating longevity in C. elegans. We found that the Y82E9BR.3 protein is localized in mitochondria and expressed in various tissues throughout development. RNAi knockdown of Y82E9BR.3 extends lifespan, decreases the accumulation of lipofuscin, and affects various physiological processes, including development delay, reproduction impairment and slow behavior. Further tissue-specific RNAi analysis showed that the intestine is a crucial organ for the longevity effects conferred by Y82E9BR.3 RNAi. Moreover, we demonstrated that lifespan extension by Y82E9BR.3 RNAi is associated with reduced mitochondrial function, as well as the suppression of complex I activity in mitochondria. Unexpectedly, Y82E9BR.3 RNAi knock down did not influence the whole-worm ATP level. Our findings first reveal the crucial role of Y82E9BR.3 in mitochondrial function and the underlying mechanism of how Y82E9BR.3 regulates lifespan in C. elegans.

    View details for DOI 10.1038/s41598-018-32025-w

    View details for Web of Science ID 000446325500048

    View details for PubMedID 30287841

    View details for PubMedCentralID PMC6172204