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Maintenance of DQB1 polymorphisms in primates.

To understand the evolution of the class II major histocompatibility complex (MHC) DQB1 locus in primates, the second exons of seven DQB1 alleles from five non-human primate species were amplified by polymerase chain reaction. Comparisons of these and other primate sequences show that no between-species diversity is greater than within-species diversity, suggesting maintenance of DQB1 alleles through the history of Old-World primates. There is a preponderance of nonsynonymous nucleotide substitutions at antigen-binding-site codons; this pattern is in marked contrast to what is seen at the closely related, presumably nonfunctional DQB2 gene. The results support the hypothesis that DQB1 polymorphism is maintained by overdominant selection relating to antigen presentation.

Animals↗

Differential expansion of neural projection systems in primate brain evolution.

Whole brain MRI scans from 11 primate species (43 individuals) spanning more than a 50-fold range in brain volume were used to determine whether the corpus callosum keeps pace with the growth of the forebrain among living anthropoid primates. Interhemispheric connectivity via the corpus callosum and anterior commissure was reduced in larger primate brains, whereas intrahemispheric connectivity was augmented. We also show that the splenium constitutes an increasing proportion of callosal area with increasing brain size. This may function to maintain rapid integration of the left and right visual space as brain size increases. These results indicate that the evolution of larger brain size in primates results in increasingly independent hemispheres.

Animals↗

Primate brain evolution: genetic and functional considerations.

Functionally distinct regions of the brain to which maternal and paternal genomes contribute differentially (through genomic imprinting) have developed differentially over phylogenetic time. While certain regions of the primate forebrain (neocortex, striatum) have expanded relative to the rest of the brain, other forebrain regions have contracted in size (hypothalamus, septum). Areas of relative expansion are those to which the maternal genome makes a substantial developmental contribution. This may be significant with respect to the importance of primate forebrain expansion in the development of complex behavioural strategies and the way in which these are deployed, especially by the matriline. In many primate societies the maintenance of social cohesion and group continuity over successive generations is dependent on the matriline, with high ranking females producing high ranking daughters that stay within the group. Regions of relative contraction are those to which the paternal genome makes a differential contribution and these are target areas for gonadal hormones, which is congruent with the diminished role for gonadal hormones in the emancipation of primate reproductive behaviour.

Animals↗

A covarion-based method for detecting molecular adaptation: application to the evolution of primate mitochondrial genomes.

A new method for detecting site-specific variation of evolutionary rate (the so-called covarion process) from protein sequence data is proposed. It involves comparing the maximum-likelihood estimates of the replacement rate of an amino acid site in distinct subtrees of a large tree. This approach allows detection of covarion at the gene or the amino acid levels. The method is applied to mammalian-mitochondrial-protein sequences. Significant covarion-like evolution is found in the (simian) primate lineage: some amino acid positions are fast-evolving (i.e. unconstrained) in non-primate mammals but slow-evolving (i.e. highly constrained) in primates, and some show the opposite pattern. Our results indicate that the mitochondrial genome of primates reached a new peak of the adaptive landscape through positive selection.

Animals↗

The problems and promise of DNA barcodes for species diagnosis of primate biomaterials.

The Integrated Primate Biomaterials and Information Resource (www.IPBIR.org) provides essential research reagents to the scientific community by establishing, verifying, maintaining, and distributing DNA and RNA derived from primate cell cultures. The IPBIR uses mitochondrial cytochrome c oxidase subunit I sequences to verify the identity of samples for quality control purposes in the accession, cell culture, DNA extraction processes and prior to shipping to end users. As a result, IPBIR is accumulating a database of 'DNA barcodes' for many species of primates. However, this quality control process is complicated by taxon specific patterns of 'universal primer' failure, as well as the amplification or co-amplification of nuclear pseudogenes of mitochondrial origins. To overcome these difficulties, taxon specific primers have been developed, and reverse transcriptase PCR is utilized to exclude these extraneous sequences from amplification. DNA barcoding of primates has applications to conservation and law enforcement. Depositing barcode sequences in a public database, along with primer sequences, trace files and associated quality scores, makes this species identification technique widely accessible. Reference DNA barcode sequences should be derived from, and linked to, specimens of known provenance in web-accessible collections in order to validate this system of molecular diagnostics.

Animals↗

Voice processing in human and non-human primates.

Humans share with non-human primates a number of voice perception abilities of crucial importance in social interactions, such as the ability to identify a conspecific individual from its vocalizations. Speech perception is likely to have evolved in our ancestors on the basis of pre-existing neural mechanisms involved in extracting behaviourally relevant information from conspecific vocalizations (CVs). Studying the neural bases of voice perception in primates thus not only has the potential to shed light on cerebral mechanisms that may be--unlike those involved in speech perception--directly homologous between species, but also has direct implications for our understanding of how speech appeared in humans. In this comparative review, we focus on behavioural and neurobiological evidence relative to two issues central to voice perception in human and non-human primates: (i) are CVs 'special', i.e. are they analysed using dedicated cerebral mechanisms not used for other sound categories, and (ii) to what extent and using what neural mechanisms do primates identify conspecific individuals from their vocalizations?

Animals↗

Embryonic stem cell lines of nonhuman primates.

Human embryonic stem (ES) cell lines have opened great potential and expectation for cell therapy and regenerative medicine. Monkey and human ES cell lines, which are very similar to each other, have been established from monkey blastocysts and surplus human blastocysts from fertility clinics. Nonhuman primate ES cell lines provide important research tools for basic and applicative research. Firstly, they provide wider aspects of investigation of the regulative mechanisms of stem cells and cell differentiation among primate species. Secondly, their usage does not need clearance or permission from the regulative rules in many countries that are associated with the ethical aspects of human ES cells, although human and nonhuman embryos and fetuses are very similar to each other. Lastly and most importantly, they are indispensable for animal models of cell therapy to test effectiveness, safety, and immunological reaction of the allogenic transplantation in a setting similar to the treatment of human diseases. So far, ES cell lines have been established from rhesus monkey (Macaca mulatta), common marmoset (Callithrix jacchus), and cynomolgus monkey (Macaca fascicularis), using blastocysts produced naturally or by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). These cell lines seem to have very similar characteristics. They express alkaline phosphatase activity and stage-specific embryonic antigen (SSEA)-4 and, in most cases, SSEA-3. Their pluripotency was confirmed by the formation of embryoid bodies and differentiation into various cell types in culture and also by the formation of teratomas that contained many types of differentiated tissues including derivatives of three germ layers after transplantation into the severe combined immunodeficiency (SCID) mice. The noneffectiveness of the leukemia inhibitory factor (LIF) signal makes culture of primate and human ES cell lines prone to undergo spontaneous differentiation and thus it is difficult to maintain these stem cell colonies. Also, these ES cells are more susceptible to various stresses, causing difficulty with subculturing using enzymatic treatment and cloning from single cells. However, with various improvements in culture methods, it is now possible to maintain stable colonies of monkey ES cells using a serum-free medium and subculturing with trypsin treatment. Under such conditions, cynomolgus monkey ES cell lines can be maintained in an undifferentiated state with a normal karyotype and pluripotency even after prolonged periods of culture over 1 year. Such progress should facilitate many aspects of stem cell research using both nonhuman primate and human ES cell lines.

Animals↗

Single haplotype analysis demonstrates rapid evolution of the killer immunoglobulin-like receptor (KIR) loci in primates.

The human killer immunoglobulin-like receptors (KIR) are encoded within the Leukocyte Receptor Complex (LRC) on chromosome 19q13.4. Here we report the comparative genomic analysis of single KIR haplotypes in two other primates. In the common chimpanzee (Pan troglodytes), seven KIR genes (ptKIRnewI, ptKIRnewII, ptKIR2DL5, ptKIRnewIII, ptKIR3DP1, ptKIR2DL4, ptKIR3DL1/2) have been identified, and five KIR genes (mmKIRnewI, mmKIR1D, mmKIR2DL4, mmKIR3DL10, mmKIR3DL1) are present in the haplotype sequenced for the rhesus macaque (Macaca mulatta). Additional cDNA analysis confirms the genes predicted from the genomic sequence and reveals the presence of a fifth novel KIR gene (mmKIRnewII) in the second haplotype of the rhesus macaque. While all known human haplotypes contain both activating and inhibitory KIR genes, only inhibitory KIR genes (characterized by long cytoplasmic tails) were found by in silico and cDNA analyses in the two primate haplotypes studied here. Comparison of the two human and the two non-human primate haplotypes demonstrates rapid diversification of the KIR gene family members, many of which have diverged in a species-specific manner. An analysis of the intronic regions of the two non-human primates reveals the presence of ancient repeat elements, which are indicative of the duplication events that have taken place since the last common ancestor.

Amino Acid Sequence↗

Analysis of primate genomic variation reveals a repeat-driven expansion of the human genome.

We performed a detailed analysis of both single-nucleotide and large insertion/deletion events based on large-scale comparison of 10.6 Mb of genomic sequence from lemur, baboon, and chimpanzee to human. Using a human genomic reference, optimal global alignments were constructed from large (>50-kb) genomic sequence clones. These alignments were examined for the pattern, frequency, and nature of mutational events. Whereas rates of single-nucleotide substitution remain relatively constant (1-2 x 10(-9) substitutions/site/year), rates of retrotransposition vary radically among different primate lineages. These differences have lead to a 15%-20% expansion of human genome size over the last 50 million years of primate evolution, 90% of it due to new retroposon insertions. Orthologous comparisons with the chimpanzee suggest that the human genome continues to significantly expand due to shifts in retrotransposition activity. Assuming that the primate genome sequence we have sampled is representative, we estimate that human euchromatin has expanded 30 Mb and 550 Mb compared to the primate genomes of chimpanzee and lemur, respectively.

Animals↗

Non-human primate models of childhood psychopathology: the promise and the limitations.

Although non-human primate models have been used previously to investigate the neurobiology of several sensory and cognitive developmental pathologies, they have been employed only sparingly to study the etiology of childhood psychopathologies for which deficits in social behavior and emotion regulation are major symptoms. Previous investigations of both adult human and non-human primates have indicated that primate social behavior and emotion are regulated by a complex neural network, in which the amygdala and orbital frontal cortex play major roles. Therefore, this review will provide information generated from the study of macaque monkeys regarding the timing of normal social and emotional behavior development, the normal pattern of anatomical and functional maturation of the amygdala and orbital frontal cortex, as well as information regarding the neural and behavioral effects of early perturbations of these two neural structures. We will also highlight 'critical periods' of macaque development, during which major refinements in the behavioral repertoire appear to coincide with significant neural maturation of the amygdala and/or orbital frontal cortex. The identification of these 'critical periods' may allow one to better predict the specific behavioral impairments likely to appear after neonatal damage to one or both of these neural areas at different time points during development. This experimental approach may provide a new and important way to inform and stimulate research on childhood psychopathologies, such as autism, schizophrenia and Williams syndrome, in which the development of normal social skills and emotional regulation is severely perturbed. Finally, the promise and limitations inherent to the use of non-human primate models of childhood psychopathology will be discussed.

Amygdala↗

Timing and tempo of primate speciation.

Published molecular clocks for primates are used to estimate typical divergence times for phylogroups (1.6 Ma), species (3.3 Ma), sister species (2.7 Ma), genera (8.9 Ma) and sister genera (8.6 Ma). Significant median differences exist between major groups (infraorders and superfamilies) for various divergence times. These data are employed to estimate typical maximum duration of speciation. Typical primate values (1.1 Ma) suggest this process to be faster than is characteristic of many vertebrates. However, after considering divergence times for hybridizing congeneric and confamilial primates, this value is likely only to estimate the commencement of prezygotic isolating mechanisms, rather than the completion of reproductive isolation. Thus, speciation typically takes around 1.0 Ma to more than 4.0 Ma to occur, depending on whether prezygotic or post-zygotic isolating mechanisms are emphasized. Typical primate genus age is around 5.3 Ma, but we note differences among major groups. In light of these estimates, the classification of humans and chimpanzees is reconsidered using a molecular yardstick approach. Three taxonomic frameworks may flow from molecular analyses, all of them having major implications for understanding the evolution of humans and chimpanzees.

Animals↗

Habitual use of the primate forelimb is reflected in the material properties of subchondral bone in the distal radius.

Bone mineral density is directly proportional to compressive strength, which affords an opportunity to estimate in vivo joint load history from the subchondral cortical plate of articular surfaces in isolated skeletal elements. Subchondral bone experiencing greater compressive loads should be of relatively greater density than subchondral bone experiencing less compressive loading. Distribution of the densest areas, either concentrated or diffuse, also may be influenced by the extent of habitual compressive loading. We evaluated subchondral bone in the distal radius of several primates whose locomotion could be characterized in one of three general ways (quadrupedal, suspensory or bipedal), each exemplifying a different manner of habitual forelimb loading (i.e. compression, tension or non-weight-bearing, respectively). We employed computed tomography osteoabsorptiometry (CT-OAM) to acquire optical densities from which false-colour maps were constructed. The false-colour maps were used to evaluate patterns in subchondral density (i.e. apparent density). Suspensory apes and bipedal humans had both smaller percentage areas and less well-defined concentrations of regions of high apparent density relative to quadrupedal primates. Quadrupedal primates exhibited a positive allometric effect of articular surface size on high-density area, whereas suspensory primates exhibited an isometric effect and bipedal humans exhibited no significant relationship between the two. A significant difference between groups characterized by predominantly compressive forelimb loading regimes vs. tensile or non-weight-bearing regimes indicates that subchondral apparent density in the distal radial articular surface distinguishes modes of habitually supporting of body mass.

Absorptiometry, Photon↗

A survey for a trypanocidal factor in primate sera.

The sera of 21 different species of primates were surveyed for the presence of a trypanocidal factor to a monomorphic human serum-sensitive clone of Trypanosoma brucei gambiense (T.b.g.); human, gorilla, baboon (2 species), and the mandrill were found to contain this factor. The factor in all the sera is in the high density lipoprotein (HDL) fraction, and has similar modes of biological action. It has been shown that the human and gorilla trypanocidal factor share cross-reactive antigenic epitopes, but do not share similar cross-reactive epitopes with the baboon and mandrill factor. There was no relationship between the presence or absence of this factor and the primate's position on the phylogenetic tree. In addition, there was also no obvious correlation between the animals' preferred diet, and the presence or absence of trypanocidal activity. The evidence to date suggests that only African ground-dwelling primates that live in tsetse endemic areas contain the trypanocidal factor. It is assumed that this factor is involved in resistance of these primates to T.b.b. We believe that the host has developed trypanocidal substances as a result of selective evolutionary pressure by the African trypanosomes.

Animals↗

Monoclonal anti-LWab and anti-D reagents recognize a number of different epitopes. Use of red cells of non-human primates.

Monoclonal antibodies (mAbs) which detect antigens on human red cells are also suitable for testing cells of other species. Such studies may reveal previously unrecognized heterogeneity in antibodies which apparently detect the same antigen on the human red cell surface. Information is also provided on specificities shared amongst several species. Here three anti-LWab and a variety of Rh-related antibodies have been tested against the red cells of various primates. One monoclonal anti-LWab antibody, BS46, reacted with the red cells of gorillas and rhesus monkeys but not those of orang-utans, baboons or marmosets. In contrast, BS56 and NIM-M8 reacted with the cells of all these species. Chimpanzee cells, however, reacted only with NIM-M8. Use of primate cells has shown that all three monoclonal anti-LWab antibodies recognize different epitopes. These observations may explain early conflicting data concerning primate cells. The difference between the monoclonal anti-D, D4, and three other anti-D antibodies, 8G2, 8D6 and 7D10, has been confirmed. The D antigen is apparently confined to the red cells of apes and humans. D4 recognizes a polymorphism in chimpanzees and 8G2, 8D6 and 7D10 recognize a polymorphism in gorillas. Two Rh-related mAbs, R6A and K70, were also investigated. R6A fails to react with Rhnull cells and reacts more weakly with homozygous-D-cells than with cells of common Rh phenotypes. K70 reacts weakly with Rhnull and -D-/-D- cells. The antigen detected by R6A is confined to the red cells of humans, gorillas and chimpanzees, while the antigen detected by K70 shows a wider species distribution. In some primates LW antigens are expressed in the absence of the determinant recognized by R6A. This phenotype has never been known to occur in humans.

Animals↗

Caloric restriction in primates.

Caloric restriction (CR) remains the only nongenetic intervention that reproducibly extends mean and maximal life span in short-lived mammalian species. This nutritional intervention also delays the onset, or slows the progression, of many age-related disease processes. The diverse effects of CR have been demonstrated many hundreds of times in laboratory rodents and other short-lived species, such as rotifers, water fleas, fish, spiders, and hamsters. Until recently, the effects of CR in longer-lived species, more closely related to humans, remained unknown. Long-term studies of aging in nonhuman primates undergoing CR have been underway at the National Institute on Aging (NIA) and the University of Wisconsin-Madison (UW) for over a decade. A number of reports from the NIA and UW colonies have shown that monkeys on CR exhibit nearly identical physiological responses as reported in laboratory rodents. Studies of various markers related to age-related diseases suggest that CR will prevent or delay the onset of cardiovascular disease, diabetes, and perhaps cancer, and preliminary data indicate that mortality due to these and other age-associated diseases may also be reduced in monkeys on CR, compared to controls. Conclusive evidence showing that CR extends life span in primates is not presently available; however, the emerging data from the ongoing primate studies strengthens the possibility that the diverse beneficial effects of CR on aging in rodents will also apply to nonhuman primates and perhaps ultimately to humans.

Aging↗

Caloric restriction in primates and relevance to humans.

Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies). To date, our results strongly suggest that the same beneficial "antiaging" and/or "antidisease" effects observed in CR rodents also occur in primates. These include lower plasma insulin levels and greater sensitivity; lower body temperatures; reduced cholesterol, triglycerides, blood pressure, and arterial stiffness; elevated HDL; and slower age-related decline in circulating levels of DHEAS. Collectively, these biomarkers suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age-related diseases and may in fact be aging more slowly than fully fed counterparts. Despite these very encouraging results, it is unlikely that most humans would be willing to maintain a 30% reduced diet for the bulk of their adult life span, even if it meant more healthy years. For this reason, we have begun to explore CR mimetics, agents that might elicit the same beneficial effects as CR, without the necessity of dieting. Our initial studies have focused on 2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that actually reduces glucose/energy flux without decreasing food intake in rats. In a six-month pilot study, 2DG lowered plasma insulin and body temperature in a manner analagous to that of CR. Thus, metabolic effects that mediate the CR mechanism can be attained pharmacologically. Doses were titrated to eliminate toxicity; a long-term longevity study is now under way. In addition, data from other laboratories suggest that at least some of the same physiological/metabolic end points that are associated with the beneficial effects of underfeeding may be obtained from other potential CR mimetic agents, some naturally occurring in food products. Much work remains to be done, but taken together, our successful results with CR in primates and 2DG administration to rats suggest that it may indeed be possible to obtain the health- and longevity-promoting effects of the former intervention without actually decreasing food intake.

Aging↗

Primates.

Nonhuman primates demonstrate marked similarities to humans in almost all aspects of their anatomy, endocrinology, and physiology. These similarities underlie the value of these animals for appropriate studies in neurobiology, immunology, pathology, reproductive biology, teratology, neonatology, endocrinology, cardiology, and psychology. Investigations with nonhuman primates has made, and continues to make, significant contributions to biomedical and behavioral research. This review provides an overview of basic and applied studies for which primates are appropriate subjects and a summary of the advantages and problems of using nonhuman primates in research.

Aging↗

Detection by PCR and isolation assays of the anaerobic intestinal spirochete Brachyspira aalborgi from the feces of captive nonhuman primates.

The purpose of this study was to investigate the presence of the anaerobic intestinal spirochetes Brachyspira aalborgi and Brachyspira pilosicoli in the feces of captive nonhuman primates (n = 35) from 19 species housed at the Zoological Gardens, Perth, Western Australia. Both spirochete species are known to infect human beings. DNA was extracted from freshly collected feces with a commercially available QIAamp DNA stool minikit and subjected to PCR protocols amplifying portions of the 16S rRNA genes of the two spirochete species. The feces were also subjected to selective culture for the spirochetes. Subsequently, feces from 62 other captive animals or birds representing 39 species at the zoo were examined by PCR to determine whether they were reservoirs of infection. Six fecal samples from individuals from four primate species (two vervet monkeys, two Tonkean macaques, one Japanese macaque, and one hamadryas baboon) tested positive in the B. aalborgi PCR. B. aalborgi was not detected by PCR in any of the other animal or bird species tested, and B. pilosicoli was not detected in the primates or any of the other animals or birds. B. aalborgi was isolated from both PCR-positive vervet monkeys. This is the first time that B. aalborgi has been isolated from nonhuman primates and the first time that it has been isolated from the feces of any species.

Animals↗