The Genome Sequence of the Chinese Hamster:Ushering In An Era of CHO Genome Engineering

CHO cells, the workhorses of the biopharmaceutical industry, are derived from the Chinese hamster, arguably making it the most economically important industrial organism. The synergistic application of high-throughput sequencing technologies, along with the existing CHO EST collection as backbone, enabled the efficient assembly of the Chinese hamster genome. The current assembly (~2.5Gb), constituting over two billion sequence reads, includes more than 25,000 annotated genes across a range of functional classes. This has allowed a global comparative analysis with the mouse, rat and human genomes. Furthermore, the investigation of regulatory features including promoters, CpG Islands and microRNAs has opened up new avenues for manipulating individual gene expression as well as genome level interventions.

In addition, this work aims to study the genetic variation underlying economically important productivity traits in CHO cells, by a comparative genomics approach, with diploid hamster DNA as reference. Further, cell line-specific functional polymorphisms have been identified utilizing RNA-Seq data from several different recombinant lines. The availability of a well-annotated Chinese hamster genome will open up many new opportunities for cell engineering and metabolic intervention for process enhancement.