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Positive selection during the diversification of class I vomeronasal receptor-like (V1RL) genes, putative pheromone receptor genes, in human and primate evolution.

Vomeronasal receptors are the major receptors for pheromones in vertebrates, and five putative type 1 vomeronasal receptors (V1RL) have been identified in humans. The evolution of the V1RL1 gene in non-human primates, and patterns of selection on V1RL genes, were investigated. The presumed ortholog of V1RL1 was sequenced from 13 species of nonhuman primate, and in eight of these species V1RL1 was a pseudogene. Phylogenetic reconstructions reveal that V1RL1 pseudogene formation occurred independently in multiple primate lineages. Using maximum likelihood estimates of dN/dS ratios in PAML, we show that V1RL genes have evolved under neutral evolution in lineages in which they became a pseudogene. In contrast, among lineages in which V1RL genes contain an open reading frame, the majority of sites are under purifying selection and a minority are under significant positive selection. These results provide an interesting case where all three categories of selection can be teased apart in the same data set using maximum likelihood methods. The finding of positive selection on V1RL genes during primate evolution provides indirect support for the hypothesis that V1RL genes have a function in species-specific pheromone detection in primates.

Amino Acid Sequence↗

Chorionic gonadotropin has a recent origin within primates and an evolutionary history of selection.

Chorionic gonadotropin (CG) is a critical signal in establishing pregnancy in humans and some other primates, but this placentally expressed hormone has not been found in other mammalian orders. The gene for one of its two subunits (CG beta subunit [CGbeta]) arose by duplication from the luteinizing hormone beta subunit gene (LHbeta), present in all mammals tested. In this study, 14 primate and related mammalian species were examined by Southern blotting and DNA sequencing to determine where in mammalian phylogeny the CGbeta gene originated. Bats (order Chiroptera), flying lemur (order Dermoptera), strepsirrhine primates, and tarsiers do not have a CGbeta gene, although they possess one copy of the LHbeta gene. The CGbeta gene first arose in the common ancestor of the anthropoid primates (New World monkeys, Old World monkeys, apes, and humans), after the anthropoids diverged from tarsiers. At least two subsequent duplication events occurred in the catarrhine primates, all of which possess multiple CGbeta copies. The LHbeta-CGbeta family of genes has undergone frequent gene conversion among the catarrhines, as well as periods of strong positive selection in the New World monkeys (platyrrhines). In addition, newly generated DNA sequences from the promoter of the CG alpha subunit gene indicate that platyrrhine monkeys use a different mechanism of alpha gene expression control than that found in catarrhines.

Amino Acid Sequence↗

A molecular view of primate phylogeny and important systematic and evolutionary questions.

Phylogenetic analysis of extensive nucleotide sequence data from primate beta-globin gene clusters elucidates the systematics and evolution of the order Primates and reveals that rates of accumulation of mutations vary by as much as a factor of seven among different primate lineages. The picture of primate phylogeny from DNA sequences clarifies many ambiguities of the morphological picture. In the molecular picture, dwarf and brown lemurs group together into superfamily Lemuroidea, Lemuroidea and Lorisoidea into suborder Strepsirhini, and Tarsius and Anthropoidea into suborder Haplorhini. The molecular picture also provides both significant evidence for a human-chimpanzee clade that narrowly excludes gorilla and overwhelming evidence for the gorilla-chimpanzee-human clade within Hominoidea. Rates of DNA sequence evolution appear to have been fastest in the early primates ancestral to Anthropoidea and next fastest on the lorisoid branch. Rates were slowest over the past 25 Myr of hominoid descent, suggesting that mechanisms lowering the mutation rate evolved in correlation with lengthened life spans.

Animals↗

The relative rate of DNA evolution in primates.

In 73 relative-rate tests involving the sequences of 17 genes between humans and six nonhuman primate taxa, there is only one significant (P less than 0.01) difference in evolutionary rate--i.e., that between human and Old World-monkey psi eta-globin genes. No evolutionary rate difference between humans and Old World monkeys is evident from analysis of 18 other genes with a total length of 6 kb. This and the comparison, between humans and other primate taxa, of new extended psi eta-globin sequences suggest that earlier observations of evolutionary-rate differences between humans and other primates were based on differences that are peculiar to psi eta-globin and that are not representative of the whole genome, which appears to be evolving at a stochastically uniform rate. This is supported by whole-genome single-copy DNA and mitochondrial DNA comparisons, neither of which shows any evidence of evolutionary-rate variation among primate taxa. Uniformity in the evolutionary rate of the DNA of primate and other mammalian taxa is inconsistent with current mammalian fossil-record interpretation. Either there has been a general slowing down in rate across lineages or the fossil record has been misinterpreted.

Animals↗

Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples.

BACKGROUND: The serotonin type 4 (5-HT4) receptor has been associated with functions of the gastrointestinal tract such as modulation of the peristaltic reflex, smooth muscle tone, intestinal secretion and visceral sensitivity. The activation of peripheral 5-HT4 receptors with agonists such as tegaserod has been shown to accelerate gastric emptying and improve symptoms of constipation in animals and humans. However, detailed data on the expression profile and on the localization of this receptor subtype are lacking so far. OBJECTIVE: To study the pattern and expression levels of 5-HT4 receptor messenger RNA expression in the gut. METHOD: Normal tissue samples were collected from the whole gastrointestinal tract of patients undergoing abdominal surgery and, in addition, of monkeys. We performed a comprehensive analysis of 5-HT4 receptor expression by quantitative reverse transcription-polymerase chain reaction, using human and non-human primate tissues from the oesophagus to the rectum. In addition, the brain and heart of non-human primates were analysed. RESULTS: Significantly higher levels of 5-HT4 receptor mRNA were measured in the human stomach, duodenum, jejunum, ileum and caecum and also in the corresponding non-human primate gut segments, ranging from 2- to 12-fold compared with the liver. No differences were found between females and males of both human and non-human primates. CONCLUSIONS: These results show 5-HT4 receptor mRNA expression throughout the gastrointestinal tract in humans and primates, and also support the preclinical and clinical findings of 5-HT4 receptors ligands exhibiting multiple effects throughout the gastrointestinal tract.

Animals↗

Correlates to traumatic brain injury in nonhuman primates.

BACKGROUND: Traumatic brain injury (TBI) is a major health problem, both in terms of the economic cost to society and the survivor's quality of life. The development of devices to protect against TBI requires criteria that relate observed injury to measurements of head kinematics. The objective of this study is to find the best statistical correlates to impact-induced TBI in nonhuman primates using a qualified, self-consistent set of historical kinematic and TBI data from impact tests on nonhuman primates. METHODS: A database was constructed and qualified from historical head impact tests on nonhuman primates. Multivariate logistic regression analysis with backwards stepwise elimination was performed. Variables considered are the peak rotational acceleration (Omegamax), the peak linear acceleration (Amax), and the number of impacts (N). RESULTS: Bivariate combinations of angular acceleration and the number of impacts are the best correlates to all modes of TBI considered, i.e., concussion, subarachnoid hemorrhage, brain contusion, and subdural hematoma. For a nonhuman primate with 100-g brain mass, the criteria that the probability of TBI is less than 10% by injury mode are:Concussion: OmegamaxN(0.84) < 70 krad/s/s SAH: OmegamaxN(0.70) < 160 krad/s/s Contusion: Omegamax N(0.35) < 160 krad/s/s SDH: Omegamax N(0.60) < 280 krad/s/s CONCLUSIONS: Based on this dataset, the best statistically based risk factor for all modes of TBI in nonhuman primates is the bivariate combination of rotational acceleration and number of impacts.

Acceleration↗

Females drive primate social evolution.

Within and across species of primates, the number of males in primate groups is correlated with the number of females. This correlation may arise owing to ecological forces operating on females, with subsequent competition among males for access to groups of females. The temporal relationship between changes in male and female group membership remains unexplored in primates and other mammalian groups. We used a phylogenetic comparative method for detecting evolutionary lag to test whether evolutionary change in the number of males lags behind change in the number of females. We found that change in male membership in primate groups is positively correlated with divergence time in pairwise comparisons. This result is consistent with male numbers adjusting to female group size and highlights the importance of focusing on females when studying primate social evolution.

Animals↗

Infanticide risk and the evolution of male-female association in primates.

Year-round association between adult males and females is common in primates, even though internal gestation and lactation predispose males to mate-desertion in the majority of mammals. Because there is little a priori support for alternative explanations, we hypothesized that permanent male-female association in primates serves to reduce the risk of infanticide by strange males whenever females and infants are closely associated. For a phylogenetic test of this hypothesis, we reconstructed the evolution of male-female and female-infant association among primates. The results of Maddison's concentrated changes test confirmed the prediction that mother-infant association, as opposed to infant parking, and female-male association did not evolve independently. Changes in litter size and activity, in contrast, were not significantly associated with evolutionary changes in male-female association. Thus, we demonstrate a fundamental link between primate life history and social behaviour, explain the most basic type of variation in primate social organization, and propose an additional determinant of social organization that may also operate in other mammals.

Animals↗

Neocortex size predicts deception rate in primates.

Human brain organization is built upon a more ancient adaptation, the large brain of simian primates: on average, monkeys and apes have brains twice as large as expected for mammals of their size, principally as a result of neocortical enlargement. Testing the adaptive benefit of this evolutionary specialization depends on finding an association between brain size and function in primates. However, most cognitive capacities have been assessed in only a restricted range of species under laboratory conditions. Deception of conspecifics in social circumstances is an exception, because a corpus of field data is available that encompasses all major lines of the primate radiation. We show that the use of deception within the primates is well predicted by the neocortical volume, when observer effort is controlled for; by contrast, neither the size of the rest of the brain nor the group size exert significant effects. These findings are consistent with the hypothesis that neocortical expansion has been driven by social challenges among the primates. Complex social manipulations such as deception are thought to be based upon rapid learning and extensive social knowledge; thus, learning in social contexts may be constrained by neocortical size.

Adaptation, Physiological↗

The nutritional consequences of foraging in primates: the relationship of nutrient intakes to nutrient requirements.

Many studies have examined the proportion of time that primates devote to feeding on various types of food, but relatively little is known about the intake rates associated with each food. However, the nutritional consequences of foraging can only be interpreted by comparing nutrient intakes with estimated nutrient requirements. The energy available to primates from ingested foods will depend both on the composition of the food and the extent to which various constituents, including fibre fractions, are digested. Both human and non-human primates have relatively low requirements for protein as a consequence of slow growth rates, small milk yields and relatively dilute milk. Because the nutrient demands of growth and reproduction are spread out over time, it appears that primates do not need to seek out foods of particularly high nutrient density, except perhaps during weaning. Although food selection in some species of primates appears to be correlated with the protein concentration of foods, it is unlikely that high dietary protein levels are required, at least when foods of balanced amino acid composition (such as leaves) are included in the diet.

Adult↗

Biomedical applications and studies of molecular evolution: a proposal for a primate genomic library resource.

The anticipated completion of two of the most biomedically relevant genomes, mouse and human, within the next three years provides an unparalleled opportunity for the large-scale exploration of genome evolution. Targeted sequencing of genomic regions in a panel of primate species and comparison to reference genomes will provide critical insight into the nature of single-base pair variation, mechanisms of chromosomal rearrangement, patterns of selection, and species adaptation. Although not recognized as model "genetic organisms" because of their longevity and low fecundity, 30 of the approximately 300 primate species are targets of biomedical research. The existence of a human reference sequence and genomic primate BAC libraries greatly facilitates the recovery of genes/genomic regions of high biological interest because of an estimated maximum neutral nucleotide sequence divergence of 25%. Primate species, therefore, may be regarded as the ideal model "genomic organisms". Based on existing BAC library resources, we propose the construction of a panel of primate BAC libraries from phylogenetic anchor species for the purpose of comparative medicine as well as studies of genome evolution.

Animals↗

Development of Y-chromosomal microsatellite markers for nonhuman primates.

We have analysed 136 newly identified human Y-chromosomal microsatellites in five (sub)species of nonhuman primates. We identified 83 male-specific loci for central chimpanzees, 82 for western chimpanzees, 67 for gorillas, 45 for orangutans and 19 loci for mandrills. Polymorphism was detected at 56 loci in central chimpanzees, 29 in western chimpanzees, 24 in western gorillas, 17 in orangutans and at three in mandrills. Success in male-specific amplification of human Y-chromosomal microsatellites in nonhuman primates was significantly negatively correlated with divergence time from the human lineage. We observed significantly more Y-chromosomal microsatellite diversity in central chimpanzees than in western chimpanzees. There were significantly more male-specific loci with longer alleles in humans than with longer alleles in the nonhuman primates; however, this significant difference disappeared when only the loci which are polymorphic in nonhuman primates were analysed, suggesting that ascertainment bias is responsible. This study provides primatologists with a large number of polymorphic, male-specific microsatellite markers that will be valuable for investigating relevant questions in behavioural ecology such as male reproductive strategies, kin-based cooperation among males and male-specific dispersal patterns in wild groups of nonhuman primates.

Animals↗

Prevalence of Epstein-Barr virus (EBV) antibodies in primate stocks of zoological gardens.

Examination of 387 serum samples from 41 primate species with two different ELISAs for the presence of IgG-antibodies against Epstein-Barr virus. Antibodies were detected in 15 out of 32 species of Old World primates and none in six species of New World primates by screening ELISA (Enzygnost, Behringwerke AG, Marburg), a testkit for human diagnostics. To avoid species-dependent factors which could influence the sensitivity of the Enzygnost assay, a competition ELISA was established. The modified test assessed antibodies in all species of Old World primates and three species of the New World primates.

Animals↗

Progress and challenges in therapies for AIDS in nonhuman primate models.

Efforts to develop animal models for human immunodeficiency virus type-1 (HIV-1) vaccine testing have focused on lentivirus infection of nonhuman primates. A long-term goal of this primate research is to utilize the models to understand the mechanisms of pathogenesis leading to AIDS. Because the time to disease is compressed relative to HIV infection in humans, therapeutic strategies and compounds can be tested in nonhuman primate models in a shorter time frame and under more controlled conditions than are possible in many clinical studies. Recent interventive studies in primates using antiviral drugs or passive immune globulin (IgG) have demonstrated that multiple log reductions in plasma virus can be achieved and sustained, with accompanying health benefits. Information gained about timing and dosage may be of utility in designing clinical studies. The development of reliable and predictable animal models for effective therapies and vaccines against AIDS remains a critical priority for primate research.

AIDS Vaccines↗

A monoclonal antibody recognizing human Thy-1: distribution on human and non-human primate haematopoietic cells.

A monoclonal antibody designated 'antibody 390' (Ab 390) with anti-human Thy-1 reactivity was prepared by the hybridoma technique from the splenocytes of BALB/c mice immunized with human fetal brain. This antibody was shown to have anti-human Thy-1 reactivity because (1) it precipitated a molecule with a molecular weight of about 24,000 daltons, (2) it had a pattern of reactivity similar to that of previously described anti-human Thy-1 antibodies and (3) purified human Thy-1 antigen specifically inhibited binding of Ab 390 to a known antigen-positive cell line. It was the intent of this study to investigate the distribution of Thy-1 on normal and malignant haematopoietic cells in humans and non-human primates. We show here that Ab 390 did not react with human peripheral blood leucocytes, bone marrow cells or splenocytes by immunofluorescence but did react with subcapsular and cortical fetal thymocytes by peroxidase-antiperoxidase immunohistology. A section of fetal spleen demonstrated staining of connective tissue and blood vessels and rare reactive lymphocytes. Adult spleen contained Thy-1-positive cells surrounding the white pulp and in the marginal zone, but single-cell suspensions of splenocytes did not react with Ab 390. Ab 390 was tested against a variety of fresh human leukaemia cells and human cell lines and was shown to react with only the acute lymphoblastic leukaemia T cell lines RPMI 8402 and HPB-MLT. Non-human primate studies revealed reactivity with a number of T cell lines from New World primates (cotton-topped and red-bellied marmosets) and peripheral blood granulocytes (owl monkey). Our studies support previous findings that suggest that human Thy-1 may be a marker for early T lymphocytes in man, and its distribution on non-human primate T cell lines suggests the same for certain species of non-human primates. Not consistent with the distribution on human cells was the demonstration of Ab 390 reactivity with owl monkey granulocytes.

Animals↗

Characterization of the genome of feline foamy virus and its proteins shows distinct features different from those of primate spumaviruses.

The genome of the feline foamy virus (FeFV) isolate FUV was characterized by molecular cloning and nucleotide sequence analysis of subgenomic proviral DNA. The overall genetic organization of FeFV and protein sequence comparisons of different FeFV genes with their counterparts from other known foamy viruses confirm that FeFV is a complex foamy virus. However, significant differences exist when FeFV is compared with primate foamy viruses. The FeFV Gag protein is smaller than that of the primate spumaviruses, mainly due to additional MA/CA sequences characteristic of the primate viruses only. Gag protein sequence motifs of the NC domain of primate foamy viruses assumed to be involved in genome encapsidation are not conserved in FeFV. FeFV Gag and Pol proteins were detected with monospecific antisera directed against Gag and Pol domains of the human foamy virus and with antisera from naturally infected cats. Proteolytic processing of the FeFV Gag precursor was incomplete, whereas more efficient proteolytic cleavage of the pre125Pro-Pol protein was observed. The active center of the FeFV protease contains a Gln that replaces an invariant Gly residue at this position in other retroviral proteases. Functional studies on FeFV gene expression directed by the promoter of the long terminal repeat showed that FeFV gene expression was strongly activated by the Bell/Tas transactivator protein. The FeFV Bell/Tas transactivator is about one-third smaller than its counterpart of primate spumaviruses. This difference is also reflected by a limited sequence similarity and only a moderate conservation of structural motifs of the different foamy virus transactivators analyzed.

Amino Acid Sequence↗

Primate population densities in three nutrient-poor amazonian terra firme forests of south-eastern Colombia.

We censused primate populations at three non-hunted 'terra firme' forests of south-eastern Colombian Amazonia. The aggregate biomass densities of diurnal primates at all sites were amongst the lowest recorded for any non-hunted forest in western Amazonia and elsewhere in the Neotropics. Densities of red howler monkeys were low, as is typical in Amazonian terra firme forests far removed from white-water rivers, and densities of woolly monkeys were 1.5-3.5 times lower than those estimated for this species in central-western Brazilian Amazonia. Densities of small to mid-sized primates except for brown capuchins (Cebus apella) and white-faced capuchins (Cebus albifrons) were similar to those of other oligotrophic Amazonian forest sites. Our results are in agreement with other studies showing that terra firme forests of lowland Amazonia typically sustain a low biomass density of primates and other mid-sized to large vertebrates. Large reserves are therefore required to assure the viability of primate populations in oligotrophic systems. Given the escalating negative impacts of human habitat disturbance and hunting in Colombian Amazonia, we urge that a baseline sampling protocol to quantify the abundance and distribution of the harvest-sensitive vertebrate fauna be established within protected areas and the large indigenous reserves so that conservation efforts can be defined and implemented.

Animals↗

Fragile sons or harassed daughters? Sex differences in mortality among juvenile primates.

In most mammals, juvenile males tend to be more vulnerable to starvation than females and consequently experience a higher mortality. This has been attributed to selection on high male growth rates in response to strong intrasexual competition. Among primates, by contrast, it has been noted that females tend to be less viable as juveniles. This has been attributed to a greater ability of juvenile males to contest for food. An alternative explanation is that there is local resource competition, and adults of the resident sex (usually females) attempt to limit the recruitment of unrelated immatures of the same sex by harassing them. These ideas are not mutually exclusive. A set of predictions from these three hypotheses was derived for two social systems and two levels of food supply. They were tested using estimates of juvenile mortality and juvenile sex ratios of non-human primates based on over 40 data sets drawn from the literature. The results indicate that the local resource competition hypothesis provides the best explanation for the observed patterns in differential juvenile mortality in primates. The contrast between the findings for primates and those for other taxa is attributed to the low growth rate of immatures and the widespread occurrence of conditions conducive to local resource competition in primates.

Animals↗