Chewsing a better assembly for COVID-19 research

The Cricetinae subfamily of hamsters, part of the large family of mouse-like rodents, contains about 20 species in several genera (Macdonald, 2010; Wilson and Mittermeier, 2017), with the exact numbers being under dispute. Hamsters live in arid or semiarid areas, encompassing parts of Europe, the Middle East, Russia, and China. Mostly herbivorous, they range in size from 5 to 28 centimeters. The golden hamster (Mesocricetus auratus), with up to 16 cm body length and 175 g in weight, is now widely used as pet and laboratory animal. Captive populations descended from a female collected in 1930 in Syria, hence it is also termed Syrian hamster, and from additional animals caught in 1971. Lifespan is up to 2 years in the wild and up to 5 in captivity.

Golden hamster, Photo by Nana-ne from Pixabay [Pixabay License]

Hamsters use their characteristic cheek pouches to collect food, which is stored in burrows, and consumed during occasionally wakings during the hibernation period. In the wild, golden hamsters, like most hamster species are solitary and aggressive toward members of their own species (an exemption may be one dwarf hamster species, Phodopus campbelli, where male animals participate in child birth and raising, which in other hamster species is done by females alone). Closest observed distances between occupied burrows was 118 meters. Hamsters feature a strong sense of smell and hearing, which are both also important for communication. Although fought in some areas since considered pests to agriculture, most hamster species are not endangered since they live in regions inhospitable to humans, and show high reproduction rates (Macdonald, 2010; Wilson and Mittermeier, 2017). Golden hamsters, and particularly male animals, were shown to have a strong preference towards and tolerance for alcohol (Lee et al., 2001).

In the laboratory, golden hamsters are an important animal model to study infectious diseases and have been used to study a plethora of virus infections including important human pathogens such as influenza A viruses (Miao et al., 2019). Upon emergence of the first severe acute respiratory distress coronavirus (SARS-CoV) in 2002/2003, Syrian hamsters were established as a disease model for coronavirus infection (Roberts et al., 2005). Based on this knowledge, this hamster species quickly became important within the research of coronavirus disease 2019 (COVID-19), caused by a related virus, called SARS-CoV-2 (Osterrieder et al., 2020; Rosa et al., 2021; Sia et al., 2020). Within COVID-19 related research, this species is widely used for studies on pathogenesis, drug development, and vaccines (Kreye et al., 2020; Lee and Lowen, 2021; Yahalom-Ronen et al., 2020).

Back in 2019, we have shared a chromosome-length upgrade to MesAur1.0, a short-read draft genome assembly generated by the Broad Institute. Today, in collaboration with a team at Max Delbruck Center for Molecular Medicine and Free University Berlin led by Emanuel Wyler and including Tatiana Borodina, Claudia Quedenau, Janine Altmüller, Markus Landthaler, Jakob Trimpert and Sandro Andreotti, we improve the genomic resources available for the species by sharing a long-read-based de novo chromosome-length genome assembly (cN50=2Mb; sN50=110Mb). The long-read sequencing was done by the MDC team with Oxford Nanopore (Promethion), with about 30x coverage and 50 kB median length of the sequences, polished with Illumina WGS data, also generated by MDC. The draft assembly was generated using wtdbg2. Hi-C data were mapped to the draft genome assembly and processed with Juicer, scaffolded with 3d-dna, followed by manually curation in JBAT. For more information see our Methods page!

Check out the new and improved chromosome-length contact map (2n=44) below. Stay tuned for new and improved annotations!

Blog post by: Emanuel Wyler, with contributions from Zhenzhen Yang

References:

Kreye, J., Reincke, S.M., Kornau, H.C., Sanchez-Sendin, E., Corman, V.M., Liu, H., Yuan, M., Wu, N.C., Zhu, X., Lee, C.D., et al. (2020). A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model. Cell 183, 1058-1069 e1019.

Lee, C.Y., and Lowen, A.C. (2021). Animal models for SARS-CoV-2. Curr Opin Virol 48, 73-81.

Lee, S.F., Chen, Z.Y., and Fong, W.P. (2001). Gender difference in enzymes related with alcohol consumption in hamster, an avid consumer of alcohol. Comp Biochem Physiol C Toxicol Pharmacol 129, 285-293.

Macdonald, D.W., ed. (2010). The encyclopedia of mammals (Oxford New York: Oxford New York : Oxford University Press).

Miao, J., Chard, L.S., Wang, Z., and Wang, Y. (2019). Syrian Hamster as an Animal Model for the Study on Infectious Diseases. Front Immunol 10, 2329.

Osterrieder, N., Bertzbach, L.D., Dietert, K., Abdelgawad, A., Vladimirova, D., Kunec, D., Hoffmann, D., Beer, M., Gruber, A.D., and Trimpert, J. (2020). Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters. Viruses 12.

Roberts, A., Vogel, L., Guarner, J., Hayes, N., Murphy, B., Zaki, S., and Subbarao, K. (2005). Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters. J Virol 79, 503-511.

Rosa, R.B., Dantas, W.M., do Nascimento, J.C.F., da Silva, M.V., de Oliveira, R.N., and Pena, L.J. (2021). In Vitro and In Vivo Models for Studying SARS-CoV-2, the Etiological Agent Responsible for COVID-19 Pandemic. Viruses 13.

Sia, S.F., Yan, L.M., Chin, A.W.H., Fung, K., Choy, K.T., Wong, A.Y.L., Kaewpreedee, P., Perera, R., Poon, L.L.M., Nicholls, J.M., et al. (2020). Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature 583, 834-838.

Wilson, D.E., and Mittermeier, R.A., eds. (2017). Handbook of the mammals of the world. Vol.7, Rodents II (Barcelona: Lynx Edicions : Conservation International : IUCN).

Yahalom-Ronen, Y., Tamir, H., Melamed, S., Politi, B., Shifman, O., Achdout, H., Vitner, E.B., Israeli, O., Milrot, E., Stein, D., et al. (2020). A single dose of recombinant VSV-G-spike vaccine provides protection against SARS-CoV-2 challenge. Nat Commun 11, 6402.

Assembly squirrules

The unstriped ground squirrel (Xerus rutilus) is a small rodent endemic to East Africa. Xerus derives from the Greek word 'xeros' meaning 'dry' which refers to the natural habitat of the unstriped ground squirrel, and rutilus is a Latin word that means 'golden-red' referencing the coat hue.

Unstriped ground squirrel by Roger Smith, [CC BY-NC 2.0], via flickr.com

The lack of longitudinal stripes makes these squirrels unique and different from other African ground squirrels. X. rutilus is relatively heavy-bodied with an average length of 225.8mm and weight of 420g. Their pelage is bristly and coarse, varying from pale tan to red-brown in colour with a conspicuous white eye ring. Populations in drier areas tend to consist of paler coloration (1).

They are diurnal, burrow-dwelling inhabitants of arid and semi-arid regions. Burrow systems are isolated from one another and typically have two to six entrances. Emergence above ground is late in relation to the sunrise, and is followed by sunbasking and grooming prior to leaving the area to forage. Their diet consists of fruits, seeds, herbaceous material, and insects (1).

Unstriped ground squirrels are non-territorial and have large, overlapping home ranges. Individuals with shared home ranges form linear dominance hierarchies, with males exhibiting dominance over females for access to food (1).

Today we share a $1K chromosome-length assembly for the unstriped ground squirrel. The draft assembly was generated by the DNA Zoo team from short insert-size PCR-free DNA-Seq data using w2rap-contigger (Clavijo et al. 2017), see (Dudchenko et al., 2018) for details.

The above draft was scaffolded to 19 chromosomes with Hi-C data generated by DNA Zoo labs using 3D-DNA (Dudchenko et al., 2017) and Juicebox Assembly Tools (Dudchenko et al., 2018). See our Methods page for more details.

We gratefully acknowledge T.C. Hsu Cryo-Zoo at the University of Texas MD Anderson Cancer Center for providing the sample for this work. The work was supported by resources provided by DNA Zoo, Aiden lab, Baylor College of Medicine (BCM), DNA Zoo Australia, The University of Western Australia (UWA). We acknowledge the Pawsey Supercomputing Centre with funding from the Australian Government and the Government of Western Australia for contributing computational resources to help with this assembly.

The following people contributed: Ashling Charles, Ruqayya Khan, Olga Dudchenko, David Weisz, Asha Multani, Sen Pathak, Richard Behringer, Parwinder Kaur, and Erez Aiden.

Citations

O’Shea, Thomas J. "Xerus rutilus." Mammalian Species 370 (1991): 1-5.

Tail of a dunnart

Dunnarts are small nocturnal mouse-sized marsupials endemic to Australia. Nineteen different species are found in habitats ranging from tropical savanna grasslands to desert sandhills and dense forests of Australia’s southeast and southwest. The fat-tailed dunnart (Sminthopsis crassicaudata) belongs to the Dasyuridae family, which also includes the little red kaluta, quolls, and the Tasmanian devil.

Photo Description: Fat-tailed Dunnart (Sminthopsis crassicaudata) Photo Credits: Photograph by Bernard Dupont licensed under CC BY-SA 2.0 [Source link: https://search.creativecommons.org/photos/4dc501a3-5501-49c3-aa3d-6c7cef71a635]

Dunnarts sleep during the day in cup-shaped nests of dried grass and leaves in fallen hollow logs or in clumps of grass, sedges and grasstrees. Their diet includes insects such as beetles, spiders, small reptiles, and amphibians. They store fat reserves in their carrot-shaped tail for times of food shortage.

The fat-tailed dunnart can survive in extreme, semi-arid environments. One of the survival techniques that it uses is daily torpor. It lowers its body temperature and metabolic rate [1] in order to reduce energy expenditure. Torpor is unaffected by alterations in photoperiod but is greatly affected by environmental conditions.

The main threats to the dunnart are habitat fragmentation, inappropriate fire regimes, and feral predators. While once common throughout Southwest Australia these diminutive marsupials are near threatened in Victoria and now confined to ‘islands’ of remnant vegetation, the result of large-scale clearing for agriculture.

The majority of its remaining habitat is privately-owned bush remnants. Dunnarts are known to be able to recolonise burnt areas readily as they are adapted to mid-successional complexes of vegetation. However, a single fire can potentially wipe out an entire population.

DNA Zoo joined forces with Prof Andrew Pask and Dr Stephen Frankenberg from University of Melbourne, Australia to deliver a much required genomic resource: a chromosome-length genome assembly for the fat-tailed dunnart. The assembly is based on the draft provided by the University of Melbourne team, led by Prof Andrew Pask. The effort has been supported by an ARC grant (DP160103683) to Pask and Frankenberg and Oz Mammals Genomics initiative, a Bioplatforms Australia framework initiative, building genomic resources for conservation through a thorough understanding of the evolution of Australia’s unique mammals that are now under threat, through climate, disease or habitat modifications.

This draft assembly was scaffolded with 548,133,068 PE Hi-C reads generated by DNA Zoo labs using 3D-DNA (Dudchenko et al., 2017) and Juicebox Assembly Tools (Dudchenko et al., 2018). See our Methods page for more details! The Hi-C work was supported by resources provided by DNA Zoo Australia, The University of Western Australia and DNA Zoo, Aiden Lab at Baylor College of Medicine with additional computational resources and support from the Pawsey Supercomputing Centre with funding from the Australian Government, the Government of Western Australia.

The following people contributed to the Hi-C chromosome-length upgrade of the project: Erez Aiden, Olga Dudchenko, Ashling Charles & Parwinder Kaur.

Citations

1. Warnecke, Lisa; James Turner; Fritz Geiser (2008). "Torpor and basking in a small arid zone marsupial". Naturwissenschaften. 95 (1): 73–78. doi:10.1007/s00114-007-0293-4.