A cheeky genome

Chinese hamsters are rodents that originated in the deserts of northern China and Mongolia. They are popular as pets throughout the world [1].

For decades, quite a few biotech drugs are produced by putting a gene for a protein into cells derived from the ovary of a Chinese hamster (CHO cell line), which then produce the protein. The history of CHO cells dates back to the 1950s, when ovarian connective tissue was harvested from the Chinese hamster and derivative cells spontaneously became immortal (Tjio, 1958). Since then, the host cells remain poorly characterized.

To facilitate CHO cell research and development, the community now relies on published draft genomes for the CHO-K1 cell line and several draft assemblies for the parent Chinese hamster. Today we share a chromosome-length upgrade to the assembly for the Chinese hamster published by Rupp et al., 2018. In order to do the upgrade, we used primary cells from the T.C. Hsu Cryo-Zoo at the University of Texas MD Anderson Cancer Center. The cells have been stored all the way back in 1977!

In agreement with previously published data, the chromosome-length assembly yielded 11 chromosomes (a very low chromosome number for a mammal!). See below how these gigantic chromosomes relate to those of other closely related rodents in the Cricetidae family (hamsters, voles, lemmings and New World rats and mice) we’ve recently assembled in the DNA Zoo: the golden hamster Mesocricetus auratus, shared here, and the canyon mouse Peromyscus crinitus, here!

Whole-genome alignment plots for the Chinese hamster (CriGri-PICR_HiC), the golden hamster (MesAur1.0_HiC) and the canyon mouse (pecr10X_v2_HiC) genome assemblies.

Introducing the T.C. Hsu Cryo-Zoo at the University of Texas MD Anderson Cancer Center

Tao-Chiuh (T.C.) Hsu, Ph.D. (17 April 1917 – 9 July 2003) was a Professor at the University of Texas MD Anderson Cancer Center, joining the institution in 1955. He was an internationally-recognized cytogeneticist, having discovered a technique using a hypotonic solution, that revolutionized chromosome preparations to determine karyotypes. He was President of the American Society for Cell Biology (1974). He has been called the "Father of modern cytogenetics".

During his tenure at MD Anderson, Dr. Hsu collected and cryo-archived fibroblasts derived from biopsies of numerous and diverse mammalian species. These specimens were collected from zoos, universities, and the wild from collaborators around the world. Fibroblasts derived from the biopsies were karyotyped and frozen for storage. The Cryo-Zoo represents a unique cell archive of genetic information.

Dr. Hsu said "If through my work children two centuries hence may be able to see extinct species live again, I feel that I will have left a worthwhile legacy."

The Cryo-Zoo is currently held by Drs. Asha Multani, Sen Pathak, and Richard Behringer in the Department of Genetics at the MD Anderson Cancer Center. More recently, Dr. Liesl Nel-Themaat and Arisa Furuta contributed to the organization and annotation of the Cryo-Zoo.

Today, we are excited to announce that the Cryo-Zoo is joining the DNA Zoo consortium. Working together, we are hoping to digitize the notebooks describing the Cryo-Zoo, grow the cells in larger numbers, make them available to the scientific community, and use them to accelerate comparative genomics and epigenomics.

Today’s assembly is an example of what we hope to achieve: we used fibroblasts first archived in the Cryo-Zoo in 1977, over half a century ago. You can read more about the Cryo-Zoo in a 1971 excerpt from the Time magazine!

Monkey business

The Japanese macaque is the northernmost-living nonhuman primate. It is found on three of the four main Japanese islands, and lives in a variety of habitats spanning subtropical forests and subarctic forests [1]. The Japanese macaque has featured prominently in culture. For example, the three wise monkeys, which warn people to “see no evil, hear no evil and speak no evil”, are Japanese macaques [2]!

Today, we share a chromosome-length genome assembly for the Japanese macaque. This genome was created in collaboration with Michal Levy-Sakin (formerly UCSF and currently at Dovetail), Pui Kwok (UCSF), Betsy Ferguson (ONPRC) and Jeff Wall (UCSF).

See below how the chromosomes in the new genome assembly compare to those of several closely related primates: the rhesus macaque Macaca mulatta, genome assembly by the Washington University School of Medicine, shared here; crab-eating macaque Macaca fascicularis, genome assembly by the International Macaca fascicularis Genome Sequencing Consortium, shared here; and humans, by the Genome Reference Consortium, latest version available here.

Whole-genome alignments of the new Japanese macaque genome assembly (Macaca_fuscata_HiC) to several previously assembled primate species: rhesus macaque (Mmul_10, ~0.5MY to common ancestor), crab-eating macaque (Macaca_fascicularis_5.0, ~1MY to common ancestor) and human (GRCh38, ~25MY to common ancestor).

It is worth pointing out that homologies in human and Japanese macaque chromosomes have been previously studies by microscopy methods, see (Weinberg et al., 1992). We copy their results below for comparison. It is easy to see that homologies calculated from genome assemblies are in agreement with the predictions made by microscopy. The assembly comparison however offers a much more comprehensive idea of intrachromosomal rearrangements that are taking place between the two species.

Fig. 2 from Weinberg et al., 1992: Idiogramatic representation of hybridization patterns of DNA derived from human chromosomes to chromosomes of Macaca fuscata. Macaque chromosome numbers are given below each chromosome, numbers on the left indicate subregions painted with the respective human chromosome specific library.