Identification of monozygotic twin chimpanzees by microsatellite analysis

Zygosity determination is important for epidemiological, biological, obstetric, and prognostic studies in both human and nonhuman primates. In this study, microsatellite loci were used to screen a pair of chimpanzee (Pan troglodytes) twins and their parents. The twins share identical alleles at all loci tested. The probability of dizygotic origin is estimated to be 2.9 x 10(-11). Even after excluding linkage of loci on the same chromosome, the probability is still low enough (3.7 x 10(-9)) to exclude dizygotic origin. MHC typing was also done on Patr-DRB and Patr-DQB loci and the twins share identical alleles at both loci, consistent with the microsatellite results. Together these results demonstrate a monozygotic origin for the chimp twins. Our results suggest that microsatellite analysis is a powerful method for zygosity determination, which can be screened reliably and efficiently. Am. J. Primatol. 52:101-106, 2000. (C) 2000 Wiley-Liss, Inc.

Genetic diversity and population history of golden monkeys (Rhinopithecus roxellana)

Golden monkey (Rhinopithecus roxellana), namely the snub-nosed monkey, is a well-known endangered primate, which distributes only in the central part of mainland China. As an effort to understand the current genetic status as well as population history of this species, we collected a sample of 32 individuals from four different regions, which cover the major habitat of this species. Forty-four allozyme loci were surveyed in our study by allozyme electrophoresis, none of which was found to be polymorphic. The void of polymorphism compared with that of other nonhuman primates is surprising particularly considering that the current population size is many times larger than that of some other endangered species. Since many independent loci are surveyed in this Study, the most plausible explanation for our observation is that the population has experienced a recent bottleneck. We used a coalescent approach to explore various scenarios of population bottleneck and concluded that the most recent bottleneck could have happened within the last 15,000 years. Moreover, the proposed simulation approach could be useful to researchers who need to analyze the non- or low-polymorphism data.

Pseudogenization of the tumor-growth promoter angiogenin in a leaf-eating monkey

Physiological functions of human genes may be studied by gene-knockout experiments in model organisms such as the mouse. This strategy relies on the existence of one-to-one gene orthology between the human and mouse. When lineage-specific gene duplication occurs and paralogous genes share a certain degree of functional redundancy, knockout mice may not provide accurate functional information on human genes. Angiogenin is a small protein that stimulates blood-vessel growth and promotes tumor development. Humans and related primates only have one angiogenin gene, while mice have three paralogous genes. This makes it difficult to generate angiogenin-knockout mice and even more difficult to interpret the genotype-phenotype relation from such animals should they be generated. We here show that in the douc langur (Pygathrix nemaeus), an Asian leaf-eating colobine monkey, the single-copy angiogenin gene has a one-nucleotide deletion in the sixth codon of the mature peptide, generating a premature stop codon. This nucleotide deletion is found in five unrelated individuals sequenced, and therefore is likely to have been fixed in the species. Five colobine species that are closely related to the douc langur have intact angiogenin genes, suggesting that the pseudogenization event was recent and unique to the douc langur lineage. This natural knockout experiment suggests that primate angiogenin is dispensable even in the wild. Further physiological studies of douc largurs may offer additional information on the role of this cancer-related gene in normal physiology of primates, including humans. Our findings also provide a strong case for the importance of evolutionary analysis in biomedical studies of gene functions. (C) 2003 Elsevier Science B.V. All rights reserved.

Evolution of the DRD2 gene haplotype and its association with alcoholism in Mexican Americans

The human D2 dopamine receptor gene (DRD2) plays a central role in the neuromodulation of appetitive behaviors and is implicated in having a possible role in susceptibility to alcoholism. We genotyped an SNP in DRD2 Exon 8 in 251 nonalcoholic, unrelated, healthy controls and 200 alcoholic Mexican Americans. The DRD2 haplotypes were analyzed using the Exon 8 genotype in combination with five other SNP genotypes, which were obtained from our previous study. The ancestral origins of the DRD2 polymorphisms have been determined by sequencing the homologous region in other higher primates. Twenty DRD2 haplotypes, defined as H1 to H20 based on their frequency from high to low, were obtained in this major minority population. The ancestral haplotype "I-132-G-C-G-A1" and two one-step mutation haplotypes were absent in our study population. The haplotype H1, "I-B1-T-C-A-A1", with the highest frequency in the population, is a three-step mutation from the ancestral form. The first five or eight major haplotypes make up 87% or 95% of the entire population, respectively. The prevalence of the haplotype H1+ (H1/H1 and H1/Hn genotypes) is significantly higher in alcoholics and alcoholic subgroups, including early onset drinkers and benders, than in their respective control groups. The Promoter -141C allele is in linkage disequilibrium (LD) with five other loci in the nonalcoholic group, but not in the alcoholic group. All of the other five loci are in LD in both the alcoholic and control groups. The DRD2 TaqI B allele is in complete LD with the allele located in intron 6. Five SNPs, Promoter -141C, TaqI B (or Intron 6), Exon 7, Exon 8, and TaqI A, are sufficient to define the DRD2 haplotypes in Mexican Americans. Our data indicate that the DRD2 haplotypes are associated with alcoholism in Mexican Americans. (c) 2005 Elsevier Inc. All rights reserved.

Episodic evolution of prolactin receptor gene in mammals: coevolution with its ligand

Divergence of proteins in signaling pathways requires ligand and receptor coevolution to maintain or improve binding affinity and/or specificity. In this paper we show a clear case of coevolution between the prolactin (PRL) gene and its receptor (prolactin receptor, PRLR) in mammals. First we observed episodic evolution of the extracellular and intracellular domains of the PRLR, which is closely consistent with that seen in PRL. Correlated evolution was demonstrated both between PRL and its receptor and between the two domains of the PRLR using Pearson's correlation coefficient. On comparing the ratio of the nonsynonymous substitution rate to synonymous substitution rate (omega=d(N)/d(S)) for each branch of the star phylogeny of mammalian PRLRs, separately for the extracellular domain (ECD) and the transmembrane domain/intracellular domain (TMD/ICD), we observed a lower omega ratio for ECD than TMD/ICD along those branches leading to pig, dog and rabbit but a higher ratio for ECD than TMD/ICD on the branches leading to primates, rodents and ruminants, on which bursts of rapid evolution were observed. These observations can be best explained by coevolution between PRL and its receptor and between the two domains of the PRLR.

Adaptive diversification of vomeronasal receptor 1 genes in rodents

The vomeronasal receptor 1 (V1R) are believed to be pheromone receptors in rodents. Here we used computational methods to identify 95 and 62 new putative V1R genes from the draft rat and mouse genome sequence, respectively. The rat V1R repertoire consists of 11 subfamilies, 10 of which are shared with the mouse, while rat appears to lack the H and I subfamilies found in mouse and possesses one unique subfamily (M). The estimations of the relative divergence times suggest that many subfamilies originated after the split of rodents and primates. The analysis also reveals that these clusters underwent an expansion very close to the split of mouse and rat. In addition, maximum likelihood analysis showed that the nonsynonymous and synonymous rate ratio for most of these clusters was much higher than one, suggesting the role of positive selection in the diversification of these duplicated V1R genes. Because V1R are thought to mediate the process of signal transduction in response to pheromone detection, we speculate that the V1R genes have evolved under positive Darwinian selection to maintain the ability to discriminate between large and complex pheromonal mixtures.

Molecular evolution of growth hormone gene family in old world monkeys and hominoids

Growth hormone is a classic molecule in the study of the molecular clock hypothesis as it exhibits a relatively constant rate of evolution in most mammalian orders except primates and artiodactyls, where dramatically enhanced rate of evolution (25-50-fold) has been reported. The rapid evolution of primate growth hormone occurred after the divergence of tarsiers and simians, but before the separation of old world monkeys (OWM) from new world monkeys (NWM). Interestingly, this event of rapid sequence evolution coincided with multiple duplications of the growth hormone gene, suggesting gene duplication as a possible cause of the accelerated sequence evolution. Here we determined 21 different GH-like sequences from four species of OWM and hominoids. Combining with published sequences from OWM and hominoids, our analysis demonstrates that multiple gene duplications and several gene conversion events both occurred in the evolutionary history of this gene family in OWM/hominoids. The episode of recent duplications of CSH-like genes in gibbon is accompanied with rapid sequence evolution likely resulting from relaxation of purifying selection. GHN genes in both hominoids and OWM are under strong purifying selection. In contrast, CSH genes in both lineages are probably not. GHV genes in OWM and hominoids evolved at different evolutionary rates and underwent different selective constraints. Our results disclosed the complex history of the primate growth hormone gene family and raised intriguing questions on the consequences of these evolutionary events. © 2005 Elsevier B.V. All rights reserved.

Origin and evolution of new exons in the rodent zinc finger protein 39 gene

The origin of new structures and functions is an important process in evolution. In the past decades, we have obtained some preliminary knowledge of the origin and evolution of new genes. However, as the basic unit of genes, the origin and evolution of exons remain unclear. Because young exons retain the footprints of origination, they can be good materials for studying origin and evolution of new exons. In this paper, we report two young exons in a zinc finger protein gene of rodents. Since they are unique sequences in mouse and rat genome and no homologous sequences were found in the orthologous genes of human and pig, the young exons might originate after the divergence of primates and rodents through exonization of intronic sequences. Strong positive selection was detected in the new exons between mouse and rat, suggesting that these exons have undergone significant functional divergence after the separation of the two species. On the other hand, population genetics data of mouse demonstrate that the new exons have been subject to functional constraint, indicating an important function of the new exons in mouse. Functional analyses suggest that these new exons encode a nuclear localization signal peptide, which may mediate new ways of nuclear protein transport. To our knowledge, this is the first example of the origin and evolution of young exons.

The Influence of Age and Sex on the Cell Counts of Peripheral Blood Leukocyte Subpopulations in Chinese Rhesus Macaques

Non-human primates such as Chinese rhesus macaques are the favorable models for preclinical study of potential therapeutic drugs, vaccines and mechanisms of human diseases. Little is known about the normal levels of leukocyte subpopulations of Chinese rhe

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

Dendritic cells (DCs) play a pivotal role in linking the innate immunity and acquired immunity in responses to pathogen. Non-human primates such as Chinese Rhesus Macaque (CRM) are the favorable models for preclinical study of potential therapeutic drugs,

黄连山自然保护区非人灵长类现状和生存威胁因素

介绍了黄连山自然保护区非人灵长类的现状。利用现有统计资料中隐含的生态信息 对自然保护区中的非人灵长类的生存威胁因素作了分析。农村人口与农民收入、粮食面积、粮 食产量、茶叶产量、水果产量和紫胶产量呈正相关;农民收入与粮食产量、茶叶产量、水果产量、 紫胶产量和橡胶面积呈正相关。农村人口、农业发展和偷猎行为是保护区非人灵长类的威胁 因素;提高农业生产效率和加强保护区管理是改善非人灵长类现状的关键。

云南孟加拉种眼镜蛇蛇毒因子在灵长类动物内应用的免疫原性研究

眼镜蛇蛇毒因子(CVF)能特异性清除机体循环中的补体C3,从而可能在防治补体介导的损伤或疾病中发挥重要的治疗作用.云南孟加拉种眼镜蛇蛇毒因子(Y-CVF)较文献报道的其他各种CVF具有更高的活性和较少的用药量.为探讨Y-CVF静脉使用是否诱导灵长类动物体内产生特异性中和抗体和异种天然抗体,给2只正常食蟹猴每两周静脉注射一次治疗剂量(0.05mg/kg)的Y-CVF,共4次,检测注射前后不同时间点血清内补体C3水平、总补体活性(CH50)、抗Y-CVF抗体和抗猪内皮细胞异种抗体的变化.结果显示,前2次注射Y-CVF后均有良好的清除补体效果,第3次注射Y-CVF后补体仪被部分灭活,第4次注射Y-CVF后则基本无效.免疫印迹和酶联免疫吸附试验均证实特异性抗Y-CVF抗体产生,且其滴度随着Y-CVF注射次数增加而递增.多次注射Y-CVF后,并没有在血清内榆测到明显的抗猪内皮细胞抗体的变化.因此,多次静脉注射Y-CVF能诱导灵长类动物产生特异性抗体,从而导致Y-CVF失效,但未发现抗α-Gal异种天然抗体明显增加.

MANDIBULAR MORPHOMETRICS AMONG MACAQUES - THE CASE OF MACACCA-THIBETANA

Recent field studies suggest that Macaca thibetana, a large endemic Chinese macaque, may be quite folivorous, distinguishing it from most other macaque species, which tend to be primarily frugivorous. To understand how this diet affects its masticatory system, we conducted a comparative morphometric study of mandibular dimensions. We took linear measurements from male and female mandibles of this species as well as four other macaques-M. fascicularis, M. nemestrina, M. arctoides, and M. assamensis-and four species of Presbytis-P. obscura, P. rubicunda, P. cristata, and P. phayrei-and subjected to them to a variety of analyses. Based on analyses of variances and discriminant analyses on each sex individually, the mandible of M. thibetana corresponds to expected patterns for folivorous primates with respect to its wide condyles and thick corpora: However, the height of the corpus and symphysis are lower, and the anteroposterior length of the condyle is longer than predicted for a folivore. In addition to interpretations specifically relating to M. thibetana, we also discuss the functional morphology of the other species in light of what is published about their diets.

Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.