Rhesus Monkey Genome Project

Image: Rhesus Macaque Macaca mulatta in Kinnerasani Wildlife Sanctuary, Andhra Pradesh, India.Image source: J.M.Garg (Own work) [GFDL or CC-BY-SA-3.0-2.5-2.0-1.0], via Wikimedia Commons

About the Project

The BCM-HGSC has sequenced the genome of the rhesus monkey (rhesus macaque, Macaca mulatta). The rhesus macaque is an Old World monkey. This primate model organism, while more distant from humans than chimpanzees or orangutans, is important for study of human disease due to its genetic, physiologic and metabolic similarity to humans. Rhesus monkeys are used for essential research in neuroscience, behavioral biology, infectious diseases, reproductive physiology, endocrinology, cardiovascular studies, pharmacology and other areas.

The Macaque Genome Sequencing Consortium is led by the Baylor College of Medicine Human Genome Sequencing Center, and in collaboration with the J. Craig Venter Institute Joint Technology Center, and the Genome Sequencing Center at Washington University, St. Louis. The goals of the project were to produce a seven-fold WGS shotgun assembly, using small insert plasmids as well as large insert clone ends from BACs, Fosmids, and 50kb linking clones. There are finishing and BAC sequencing components of the project to investigate interesting regions for human diseases and to highlight primate evolution.

The rhesus macaque genome sequencing project began in 2002 with consultations between the BCM-HGSC and primate researchers. The project was compelling both because of the intense interest in this organism as a biomedical research model—including SIV and AIDS research—and because of its unique placement in the evolutionary tree relative to the human. A white paper was given high priority in early 2003 by NHGRI. The project was a 5x WGS draft assembly with additional finished regions (up to 500 Mb) and an undefined BAC component, as needed to ensure overall quality. A BAC library from a male was available and the Genome Centre in Vancouver expressed interest in building a fingerprint map. New methods of mapping BACs by pool genomic indexing (PGI) were developed.

The Southwest National Primate Research Center provided DNA from a single female rhesus. BCM-HGSC and Wash U each sequenced 2.5x WGS and JCVI 1x. After sufficient data for 4x coverage, an "interim assembly" was generated by the HGSC to test overall fidelity of the work. This was displayed on the UCSC browser in April 2005. After the WGS data was complete, independent assemblies were performed at each sequencing center using different approaches. A working group was convened to coordinate evaluation and comparison of each assembly and guide melding into a single assembly. The "melded assembly" used the fingerprint map and, at the very highest level (i.e., super-contig placement on the chromosomes), it referred to the human sequence. Statistically this is a high quality 5x WGS assembly, rivaling the rat, which contained a complete BAC scaffold. This assembly, released in Feb 2006, was used for gene predictions, and ongoing analysis.

The BCM-HGSC is currently sequencing more than 100 rhesus macaques from several different NIH-funded research colonies in order to identify and characterize genetic variation in this species. 

The sequencing and comparative analysis is funded by the National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH).

Genomic Resources

Related Publications

Oler JA, Fox AS, Shelton SE, Rogers J, Dyer TD, Davidson RJ, et al. Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature. 2010 ;466(7308):864-8.

Kanthaswamy S, Capitanio JP, Dubay CJ, Ferguson B, Folks T, Ha JC, et al. Resources for genetic management and genomics research on non-human primates at the National Primate Research Centers (NPRCs). J Med Primatol. 2009 ;38 Suppl 1:17-23.

Christian BT, Fox AS, Oler JA, Vandehey NT, Murali D, Rogers J, et al. Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET. Neuroimage. 2009 ;47(4):1230-6.

Chen D, Ge J, Wang L, Gao Q, Ma P, Li N, et al. A simple and evolutional approach proven to recanalise the nasolacrimal duct obstruction. Br J Ophthalmol. 2009 ;93(11):1438-43.

Degenhardt JD, de Candia P, Chabot A, Schwartz S, Henderson L, Ling B, et al. Copy number variation of CCL3-like genes affects rate of progression to simian-AIDS in Rhesus Macaques (Macaca mulatta). PLoS Genet. 2009 ;5(1):e1000346.

Mubiru JN, Hubbard GB, Dick EJ, Furman J, Troyer DA, Rogers J. Nonhuman primates as models for studies of prostate specific antigen and prostatic diseases. Prostate. 2008 ;68(14):1546-54.

Rogers J, Shelton SE, Shelledy W, Garcia R, Kalin NH. Genetic influences on behavioral inhibition and anxiety in juvenile rhesus macaques. Genes Brain Behav. 2008 ;7(4):463-9.

Hernandez RD, Hubisz MJ, Wheeler DA, Smith DG, Ferguson B, Rogers J, et al. Demographic histories and patterns of linkage disequilibrium in Chinese and Indian rhesus macaques. Science. 2007 ;316(5822):240-3.

R Harris A, Rogers J, Milosavljevic A. Human-specific changes of genome structure detected by genomic triangulation. Science. 2007 ;316(5822):235-7.