Project description:The rhesus macaque is an abundant species of Old World monkeys and a valuable model organism for biomedical research due to its close phylogenetic relationship to humans. Copy number variation is one of the main sources of genomic diversity within and between species and a widely recognized cause of inter-individual differences in disease risk. However, copy number differences among rhesus macaques and between the human and macaque genomes, as well as the relevance of this diversity to research involving this nonhuman primate, remain understudied. Here we present a high-resolution map of sequence copy number for the rhesus macaque genome constructed from a dataset of 198 individuals. Our results show that about one-eighth of the rhesus macaque reference genome is composed of recently duplicated regions, either copy number variable regions or fixed duplications. Comparison with human genomic copy number maps based on previously published data shows that, despite overall similarities in the genome-wide distribution of these regions, there are specific differences at the chromosome level. Some of these create differences in the copy number profile between human disease genes and their rhesus macaque orthologs. Our results highlight the importance of addressing the number of copies of target genes in the design of experiments and cautions against human-centered assumptions in research conducted with model organisms. Overall, we present a genome-wide copy number map from a large sample of rhesus macaque individuals representing an important novel contribution concerning the evolution of copy number in primate genomes.
Project description:Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance, location, and spacing of the vertical array. We next asked whether monkeys show a spatially-oriented number mapping by testing their responses to the same five-element stimulus array rotated ninety degrees into a horizontal line. In these horizontal probe trials, monkeys preferentially selected the fourth position from the left, but not the fourth position from the right. Our results indicate that rhesus macaques map number onto space, suggesting that the association between number and space in human cognition is not purely a result of cultural experience and instead has deep evolutionary roots.
Project description:Primate bocaparvovirus (BOV) is a possible cause of respiratory disorders and gastroenteritis in humans. However, the diversity and evolution of these viruses remain largely unknown, despite the identification of a growing number of BOVs in non-human primates (NHPs). Here, we report the identification of a novel BOV (provisionally named Macaca mulatta bocaparvovirus [MmBOV]) in the feces of wild Macaca mulatta in China by viral metagenomic analysis. Seven of 400 fecal samples from Macaca mulatta were positive for MmBOV. An almost complete genome sequence of 4,831 nucleotides was obtained, which had genomic organization and protein motifs similar to human bocaviruses (HOBVs), and shared characteristically low G/C content and weak codon usage bias. Sequence analyses of NS1, NP1, and VP1 revealed that MmBOV was most closely related to HBOV4 of Primate bocaparvovirus 2 (approximately 68.4%/70.6%, 73.3%/67.6%, and 70.4%/73.1% nucleotide/amino acid identities, respectively). Additionally, phylogenetic analysis revealed that MmBOV formed an independent peripheral branch, but clustered closely with those of the Primate bocaparvovirus species in the BOV genus (particularly HBOV4). These data strongly suggest that HBOV4 originated from NHP bocaparvoviruses around 200-300 years ago, and that NHPs may act as HBOV reservoirs. Following the International Committee of Taxonomy for Viruses guidelines, we propose MmBOV as a new species (tentatively named Primate bocaparvovirus 3) in the genus Bocaparvovirus, which is the first report of a novel species of primate BOV. Our data facilitate future research on the genetic diversity and evolution of primate bocaparvoviruses and highlight the importance of bocaparvovirus surveys in wild NHPs.
Project description:BACKGROUND: The cattle MHC is termed the bovine leukocyte antigen (BoLA) and, along with the MHCs of other ruminants, is unique in its genomic organization. Consequently, correct and reliable gene maps and sequence information are critical to the study of the BoLA region. The bovine genome sequencing project has produced two assemblies (Btau_3.1 and 4.0) that differ substantially from each other and from conventional gene maps in the BoLA region. To independently compare the accuracies of the different sequence assemblies, we have generated a high resolution map of BoLA using a 12,000rad radiation hybrid panel. Seventy-seven unique sequence tagged site (STS) markers chosen at approximately 50 kb intervals from the Btau 2.0 assembly and spanning the IIa-III-I and IIb regions of the bovine MHC were mapped on a 12,000rad bovine radiation hybrid (RH) panel to evaluate the different assemblies of the bovine genome sequence. RESULTS: Analysis of the data generated a high resolution RH map of BoLA that was significantly different from the Btau_3.1 assembly of the bovine genome but in good agreement with the Btau_4.0 assembly. Of the few discordancies between the RH map and Btau_4.0, most could be attributed to closely spaced markers that could not be precisely ordered in the RH panel. One probable incorrectly-assembled sequence and three missing sequences were noted in the Btau_4.0 assembly. The RH map of BoLA is also highly concordant with the sequence-based map of HLA (NCBI build 36) when reordered to account for the ancestral inversion in the ruminant MHC. CONCLUSION: These results strongly suggest that studies using Btau_3.1 for analyses of the BoLA region should be reevaluated in light of the Btau_4.0 assembly and indicate that additional research is needed to produce a complete assembly of the BoLA genomic sequences.
Project description:Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.
Project description:Mass spectrometry based proteomics has facilitated sperm composition studies in several mammalian species but no studies have been undertaken in non-human primate species. Here we report the analysis of the 1247 proteins that comprise the Rhesus macaque (Macaca mulatta) sperm proteome (termed the MacSP). Comparative analysis with previously characterized mouse and human sperm proteomes reveals substantial levels of orthology (47% and 40% respectively) and widespread overlap of functional categories based on Gene Ontology analyses. Approximately 10% of macaque sperm genes (113/1247) are significantly under-expressed in the testis as compared with other tissues, which may reflect proteins specifically acquired during epididymal maturation. Phylogenetic and genomic analyses of three MacSP ADAMs (A-Disintegrin and Metalloprotease proteins), ADAM18-, 20- and 21-like, provides empirical support for sperm genes functioning in non-human primate taxa which have been subsequently lost in the lineages leading to humans. The MacSP contains proteasome proteins of the 20S core subunit, the 19S proteasome activator complex and an alternate proteasome activator PA200, raising the possibility that proteasome activity is present in mature sperm. Robust empirical characterization of the Rhesus sperm proteome should greatly expand the possibility for targeted molecular studies of spermatogenesis and fertilization in a commonly used model species for human infertility.
Project description:AIM:To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum. METHODS:Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological, histological assays. RESULTS:Serum HGV RNA was detectable in all the 3 Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohis-tochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes. RT-PCR and quantitative PCR results showed that HGV could replicate in liver. CONCLUSION:The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.
Project description:Maximizing animal wellbeing by minimizing drug-related side effects is a key consideration when choosing pharmaceutical agents for chemical restraint in nonhuman primates. One drug combination that may promote this ideology is butorphanol (27.3 mg/mL), azaperone (9.1 mg/mL), and medetomidine (10.9 mg/mL; BAM). Based on results from a pilot study, 2 doses of BAM (16 and 24 ?L/kg IM) were compared in healthy, 3-y-old rhesus macaques. Physiologic parameters and anesthetic quality were assessed and recorded every 5 min. Experimental endpoints were established for hypoxemia (85% or less peripheral oxygen saturation with oxygen supplementation), pulse rate (80 bpm or less for 2 consecutive readings), mean arterial pressure (MAP; 50 mm Hg or less), and hypothermia (97 °F or less); if any endpoint was achieved, medetomidine was reversed by using atipamezole (0.22 mg/kg IM). Both BAM doses resulted in immobilization of all animals with no clinically significant differences between groups. All animals initially exhibited hypoxemia that resolved with oxygen supplementation. Regardless of dose, most macaques (71%) reached established experimental endpoints for bradycardia (62 to 80 bpm) or hypotension (44 to 50 mm Hg MAP). Given the results of this study, our recommendation regarding the use of 16- or 24-?L/kg BAM for immobilizing rhesus macaques is dependent on caution regarding cardiopulmonary parameters and the provision of supplemental oxygen.
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that are critical in post-transcriptional regulation. Macaca mulatta is an important nonhuman primate that is often used in basic and translational researches. However, the annotation of miRNAs in Macaca mulatta is far from complete, and there are no reports of miRNA editing events in Macaca mulatta, although editing may affect the biogenesis or functions of the miRNAs. To improve miRNA annotation and to reveal editing events of miRNAs in Macaca mulatta, we generated 12 small RNA profiles from eight tissues and performed comprehensive analysis of these profiles. We identified 479 conserved pre-miRNAs that have not been reported in Macaca mulatta and 17 species specific miRNAs. Furthermore, we identified 3386 editing sites with significant editing levels from 471 pre-miRNAs after analyzing the 12 self-generated and 58 additional published sRNA-seq profiles from 17 different types of organs or tissues. In addition to 16 conserved A-to-I editing sites, we identified five conserved C-to-U editing sites in miRNAs of Macaca mulatta and Homo sapiens. We also identified 11 SNPs in the miRNAs of Macaca mulatta. The analysis of the potential targets of 69 miRNAs with editing or mutation events in their seed regions suggest that these editing or mutation events severely changed their targets and their potential functions. These results significantly increase our understanding of miRNAs and their mutation/editing events in Macaca mulatta.