Cited by 380Viral Infectious Diseases and Gene Expression in InsectsGenomics and Phylogenetic StudiesAnimal Genetics and Reproduction

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome

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Lewis, Nathan E, Liu, Xin, Li, Yuxiang, Nagarajan, Harish, Yerganian, George, O'Brien, Edward, Bordbar, Aarash, Roth, Anne M +13 more·2013·Nature Biotechnology

Abstract

Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this genetic diversity highlight the value of the hamster genome as the reference upon which CHO cells can be studied and engineered for protein production.

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  • The publication of the CHO-K1 genome sequence in 2011, followed by the publication of two Chinese hamster and six CHO cell line genomes in 2013, bring new opportunities in developing and engineering CHO cells for improved glycoprotein production.

    “The publication of the CHO-K1 genome sequence in 2011, followed by the publication of two Chinese hamster and six CHO cell line genomes in 2013, bring new opportunities in developing and engineering CHO cells for improved glycoprotein production (Xu et al., 2011;Brinkrolf et al., 2013;Lewis et al., 2013).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Lewis et al., 2013

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  1. Kildegaard, H.F., Baycin-Hizal, D., Lewis, N.E. & Betenbaugh, M.J. The emerging CHO systems biology era: harnessing the 'omics revolution for biotechnology. Curr. Opin. Biotechnol. doi:10.1016/j.copbio.2013.02.007 (20 March 2013). · DOI · Paper page
  2. Kent, W.J., Baertsch, R., Hinrichs, A., Miller, W. & Haussler, D. Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl. Acad. Sci. USA 100, 11484-11489 (2003).

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Authors
Lewis, N. E., Liu, X., Li, Y., Nagarajan, H., Yerganian, G., O'Brien, E., Bordbar, A., Roth, A. M., Rosenbloom, J., Bian, C., Xie, M., Chen, W., Li, N., Baycin-Hizal, D., Latif, H., Forster, J., Betenbaugh, M. J., Famili, I., Xu, X., Wang, J., & Palsson, B. O.
Affiliations
  • Qualcomm (United States) (US)
  • BGI Group (China) (CN)
  • Brandeis University (US)
  • Johns Hopkins University (US)
Corresponding author
Wang, Jun
Venue
Nature Biotechnology
Published
2013-07-21
Volume
31
Issue
8
Pages
759-765
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2127173397
Cited by
380
References
8
Citations by year
2026: 11 · 2025: 15 · 2024: 13 · 2023: 13 · 2022: 21 · 2021: 36 · 2020: 23 · 2019: 27 · 2018: 50 · 2017: 35 · 2016: 30 · 2015: 55 · 2014: 41 · 2013: 7 · 2012: 1
FWCI
19.87
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
Funders
Novo Nordisk Fonden (NNF10CC1016517)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
Keywords
CHO cells, Chinese hamster, draft genome sequence, single nucleotide polymorphisms, copy number variation, indels, CHO-K1 cells, apoptosis-related genes, bioprocessing, therapeutic protein production
MeSH terms
Animals, Base Sequence, Chromosome Mapping, Cricetulus, Female, Cricetinae, Humans, Molecular Sequence Data, Genetic Variation, CHO Cells, Genome, Sequence Analysis, DNA

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