Rhesus Monkey Genome Project

[field_page_main_image-alt]

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

Dray BK, Raveendran M, R Harris A, Benavides F, Gray SB, Perez CJ, et al. Mismatch repair gene mutations lead to lynch syndrome colorectal cancer in rhesus macaques. Genes Cancer. 2018 ;9(3-4):142-152.

Brammer DW, Gillespie PJ, Tian M, Young D, Raveendran M, Williams LE, et al. MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques. Proc Natl Acad Sci U S A. 2018 ;115(11):2806-2811.

Prall TM, Graham ME, Karl JA, Wiseman RW, Ericsen AJ, Raveendran M, et al. Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques. Immunogenetics. 2017 ;69(5):325-339.

Xue C, Raveendran M, R Harris A, Fawcett GL, Liu X, White S, et al. The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences. Genome Res. 2016 ;26(12):1651-1662.

Bakken TE, Miller JA, Ding S-L, Sunkin SM, Smith KA, Ng L, et al. A comprehensive transcriptional map of primate brain development. Nature. 2016 ;535(7612):367-75.

Zhdanova IV, Rogers J, González-Martínez J, Farrer LA. The ticking clock of Cayo Santiago macaques and its implications for understanding human circadian rhythm disorders. Am J Primatol. 2016 ;78(1):117-26.

Peng X, Thierry-Mieg J, Thierry-Mieg D, Nishida A, Pipes L, Bozinoski M, et al. Tissue-specific transcriptome sequencing analysis expands the non-human primate reference transcriptome resource (NHPRTR). Nucleic Acids Res. 2015 ;43(Database issue):D737-42.

Fawcett GL, Dettmer AM, Kay D, Raveendran M, Higley JD, Ryan ND, et al. Quantitative Genetics of Response to Novelty and Other Stimuli by Infant Rhesus Macaques (Macaca mulatta) Across Three Behavioral Assessments. Int J Primatol. 2014 ;35(1):325-339.

Rogers J, Raveendran M, Fawcett GL, Fox AS, Shelton SE, Oler JA, et al. CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression. Mol Psychiatry. 2013 ;18(6):700-7.

Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Graves T, Fulton RS, et al. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature. 2012 ;483(7387):82-6.