Variation In Macaques Research Articles

Multi-scale hierarchical brain regions detect individual and interspecies variations of structural connectivity in macaque monkeys and humans

Macaques are representative animal models in translational research. However, the distinct shape and location of the brain regions between macaques and humans prevents us from comparing the brain structure directly. Here, we calculated structural connectivity (SC) with multi-scale hierarchical regions of interest (ROIs) to parcel out human and macaque brain into 8 (level 1 ROIs), 28 (level 2 ROIs), or 46 (level 3 ROIs) regions, which consist of anatomically and functionally defined level 4 ROIs (around 100 parcellation of the brain). The SC with the level 1 ROIs showed lower individual and interspecies variation in macaques and humans. SC with level 2 and 3 ROIs shows that the several regions in frontal, temporal and parietal lobe show distinct connectivity between macaques and humans. Lateral frontal cortex, motor cortex and auditory cortex were shown to be important areas for interspecies differences. These results provide insights to use macaques as animal models for translational study.

Intrageneric taxonomic distinction based on morphological variation in the macaque (Macaca) skeleton.

Taxonomic classification is important for understanding the natural world, yet current methods for species assessment often focus on craniodental morphology rather than the entire skeleton. Moreover, it is currently unknown how much variation could, or should, exist intragenerically. Here, we tested whether taxonomy can be accurately predicted based on patterns of morphological variation in macaques (H1 ) and whether postcranial bones reflect subgeneric macaque taxonomy similarly, or better, than the cranium (H2 ). Data included 3D scans of cranial and postcranial bones for eight macaque species (Macaca arctoides, Macaca fascicularis, Macaca fuscata, Macaca mulatta, Macaca nemestrina, Macaca nigra, Macaca radiata, and Macaca sylvanus). Fixed anatomical and semilandmarks were applied to scans of eight skeletal elements (crania = 45; mandible = 31; scapula = 66; humerus = 38; radius = 33; os coxa = 28; femur = 40; tibia = 40). For each skeletal element, regression analyses were performed to minimize the effects of sexual dimorphism. Between-groups principal components analysis was used to visualize the major patterns of among-species morphological variation, while the strength of correct taxon classification was measured with discriminant function analysis. Results suggested accepting the alternate hypothesis that different macaque species can be distinguished morphologically. Both cranial and many postcranial elements appeared to possess a taxonomic signal, and the limb bones-especially the upper limb-are reported to be more useful for taxonomic assessment than previously realized. Theoretically, certain behaviors and/or ecogeographical factors, as well as phylogeny, influenced skeletal morphology in macaques, likely contributing to taxonomic distinctions among different species.

The orthologs of HLA-DQ and -DP genes display abundant levels of variability in macaque species.

The human major histocompatibility complex (MHC) region encodes three types of class II molecules designated HLA-DR, -DQ, and -DP. Both the HLA-DQ and -DP gene region comprise a duplicated tandem of A and B genes, whereas in macaques, only one set of genes is present per region. A substantial sequencing project on the DQ and DP genes in various macaque populations resulted in the detection of previously 304 unreported full-length alleles. Phylogenetic studies showed that humans and macaques share trans-species lineages for the DQA1 and DQB1 genes, whereas the DPA1 and DPB1 lineages in macaques appear to be species-specific. Amino acid variability plot analyses revealed that each of the four genes displays more allelic variation in macaques than is encountered in humans. Moreover, the numbers of different amino acids at certain positions in the encoded proteins are higher than in humans. This phenomenon is remarkably prominent at the contact positions of the peptide-binding sites of the deduced macaque DPβ-chains. These differences in the MHC class II DP regions of macaques and humans suggest separate evolutionary mechanisms in the generation of diversity.

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences.

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.

Functional and behavioral consequences of DRD4 genetic variation in macaques

Functional and behavioral consequences of DRD4 genetic variation in macaques

MhcDRB‐sequences from cynomolgus macaques (Macaca fascicularis) of different origin

Cynomolgus macaques are frequently used in biomedical research. However, in contrast to their closest relative, the rhesus macaque, little is known about their Mhc genes except for the DQB1 locus. In this study, 33 DRB-sequences belonging to 17 allelic lineages were detected in a total of 68 macaques, 58 originating from Mauritius and 10 from China. The majority of the sequences were detected in the few macaques from China, confirming the low degree of genetic variation in macaques from Mauritius. In summary, the DRB region in cynomolgus macaques is polymorphic. The sequences belong in general to the same allelic lineages as in their closest relative, the rhesus macaque. Two exon 2 DNA sequences were identical in both species and may represent a trans-species origin. In addition, protein sequences of members of the DRB*W1 lineage seem to be rather conserved in the three macaque species examined so far. Six DRB-haplotypes were detected in the macaques from Mauritius. While single DRB-alleles or some protein sequences seemed to be conserved among macaque species, we could not detect any evidence for a trans-species conservation of a complete DRB region. Overall, the data indicate that reorganization of the DRB region by recombination is a major force in creating diversity in cynomolgus macaques as it is in rhesus macaques.

Hemoglobin α-chain variation in macaques: Primary structures of the αI and αII chains from the adult hemoglobins of Malaysian Macaca nemestrina

The complete primary structures of each of the two α chains commonly found in the adult hemoglobins of Malaysian Macaca nemestrina (pig-tailed macaques) were obtained from the intact chains and five fragments produced by two nonenzymatic and three enzymatic cleavage reactions. The two chains differ at a single site, the α I chains having a glutaminyl residue and the α II chains having a histidinyl residue in position 78. Both chains differ from their human counterpart at five positions, the extent of divergence being similar to that observed for most of the α chains from other species of Macaca that have been analyzed to date. Elucidation of the structural difference between the α I and α II chains demonstrates that the high degree of heterogeneity observed among the hemoglobin phenotypes of M. nemestrina is a consequence of underlying genetic variability and not a result of postsynthetic modification of genetically identical proteins. Comparisons with the hemoglobin phenotypes found in other species of Macaca support the contention that chromosomes bearing linked α I and α II genes, as well as those bearing single α I and α II alleles, combine in zygotes to produce the phenotypic variation observed in members of Malaysian populations of M. nemestrina.