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PubMed1998

Emergence of a brain-expressed variant melanin-concentrating hormone gene during higher primate evolution: a gene "in search of a function".

Two related but distinct melanin-concentrating hormone (MCH) gene systems, i.e., the authentic and variant genes, have been characterized in the human, while only a single MCH gene has been found in the rat. We previously established that the variant gene corresponds to exon-I-deleted copies of the authentic gene mapped on chromosomes 5 and 12, respectively. In this report, we examined the expression of the authentic and variant MCH genes in the human brain. Mature mRNAs of the authentic MCH gene appeared to be predominantly expressed in the hypothalamus, whereas putative unprocessed transcripts of the variant MCH gene were found in other brain areas but not in the hypothalamus. Several products of the variant MCH gene were identified by RACE-PCR in the fetal human brain. One of these transcripts encoded a putative protein of 72 amino acids, while another transcript may potentially generate a protein of 35 amino acids. Thereafter, we explored the question of MCH gene transposition during Primate evolution. Southern blotting, PCR analyses using several genomic DNAs of Primates, and in situ hybridization on metaphase chromosomes led us to define at least three types of genetic events associated with the emergence of the variant MCH gene: (1) translocation of an exon II-exon III copy of the authentic MCH gene onto the equivalent of the human chromosome 5p arm of Anthropoidea ancestors (between 25 and 55 MYA); (2) exon II truncation and mutations before divergence of the Hylobatidae (about 15 MYA); and (3) duplication of the variant gene on the equivalent of the human chromosome 5p and 5q arms in the Hominidae, i.e., 5-10 MYA. Taken together, these results support the hypothesis that transposition/gene rearrangement processes could underlie the evolutionary emergence of new MCH-related genes expressed differentially in the brains of higher Primates, illustrating the concept of genes "in search of function" instead of true "pseudogenes."

Animals↗

PubMed1999

Rapid evolution of a primate sperm protein: relaxation of functional constraint or positive Darwinian selection?

Protamines are arginine-rich proteins that replace histones and bind sperm DNA during spermatogenesis in vertebrates. Previous studies have shown that protamine exons evolve faster than does the protamine intron. It has been suggested that this is a result of a relaxation of functional constraint. However, a more likely explanation is that the evolutionary rate of exons has been accelerated by positive Darwinian selection, because introns are generally believed to evolve in a neutral fashion. Therefore, we examined the possibility that positive selection has been acting on the protamine genes of three groups of placental mammals: primates (hominoids and Old World monkeys), rodents (mice, rats, and guinea pigs), and pecoran ruminants (deer and bovids). We found that the nucleotide substitution rate at nonsynonymous sites is significantly higher than the rate at synonymous and intron sites for protamine P1 of hominoids and Old World monkeys. This result suggests that positive selection has been operating on protamine P1 of these species. In contrast, no clear-cut evidence of positive selection was found for protamine P1 of ruminants and rodents or protamine P2 of primates. The agent of positive selection on primate protamine P1 remains unknown, though sperm competition is a possibility. Further investigations on the function and intraspecific polymorphism of this protein are needed in order to identify the selection agent.

Animals↗

PubMed1984

Individual and evolutionary variation of primate ribosomal DNA transcription initiation regions.

A 16-kilobase region surrounding the transcription initiation site for ribosomal DNA and including the entire ribosomal DNA transcription unit has been characterized in man and compared in higher primates. Restriction analysis of ribosomal DNA from the pygmy chimpanzee (Pan paniscus), the common chimpanzee (Pan troglodytes), the gorilla (Gorilla gorilla), the orangutan (Pongo pygmaeus), the gibbon (Hylobates lar), and the rhesus monkey (Macaca mulatta) allows a primate phylogeny to be constructed based on ribosomal DNA structure. Individual variation and methylation are demonstrated in the ribosomal DNA repeats of all primates examined. Restriction analysis with HincII endonuclease suggests cleavage at sites containing methylated CpG and adds the SalI/HincII pair to those enzymes useful for studying DNA modification.

Animals↗

PubMed2004

Progress with nonhuman primate embryonic stem cells.

Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.

Animals↗

PubMed2004

Imaging serotonin transporters with 123I-ADAM brain SPECT in healthy non-human primates.

BACKGROUND: Serotonin transporters (SERTs) play a major role in modulating serotonergic neuronal function and are the target of many antidepressant drugs used in neuro-psychiatric disorders. To gain more information on the temporal distribution of SERTs, 2-([2-([dimethylamino]methyl)phenoxyl]thio)-5-[I]iodophenylamine (I-ADAM) single photon emission computed tomography (SPECT) was utilized in an in vivo imaging study using non-human primates. METHODS: Two female monkeys (Macaca cyclopis) were studied. Eight brain SPECT imaging examinations, each 30 min in duration, were obtained after injection of 185 MBq of I-ADAM. Images were obtained using a dual-head gamma camera equipped with ultra-high resolution fan-beam collimators. In addition to visual inspection, the radio-uptake and specific uptake ratios (SURs) of midbrain (MB), thalamus (TH), striatum (ST), temporal and frontal cortices and the whole brain in reference to the corresponding magnetic resonance image at the eight time points were measured. The SUR of MB, using cerebellum (CB) as the reference tissue, was calculated as (MB - CB)/CB, in mean counts/pixel. The SURs of the other brain regions were similarly measured. RESULTS: There was relatively high uptake of I-ADAM in the MB and TH, moderate uptake in ST, lower uptake in the cerebral cortex, and almost no uptake in the CB. The image of MB could be easily identified at the first 30 min time point. It appeared that the SURs of MB, TH and ST reached equilibrium around 210 min after injection. No adverse reactions of the primates were found during and after imaging. Brain distribution of I-ADAM in the primate appeared consistent with the known distribution of SERTs. CONCLUSION: In conjunction with a high SUR in MB, TH and ST, we speculate that I-ADAM may be a potential radioligand for SPECT studies of serotonin transporters in humans.

Animals↗

PubMed2005

Strategies for tolerance induction in nonhuman primates.

Recent advances in the field of reconstructive surgery and immunology resulted in increased interest in composite tissue allograft (CTA) transplantation. Up to date, more than 50 CTA transplants have been reported in humans. A significant number of experimental studies on CTA transplants under different protocols of tolerance-inducting strategies have been reported in small-animal models. There is however, a limited number of CTA transplants performed in nonhuman primates. To reach the ultimate clinical success in CTA transplantation, more experimental studies on tolerance induction in nonhuman primates are needed to apply these immunomodulatory protocols to CTA transplants in humans. In this review, strategies for tolerance induction in the nonhuman primate model in solid organ and CTA transplants are presented in 3 major categories: chimerism induction, T-cell depletion, and costimulatory receptor blockade.

Animals↗

PubMed2005

Neocortex evolution in primates: the "social brain" is for females.

According to the social intelligence hypothesis, relative neocortex size should be directly related to the degree of social complexity. This hypothesis has found support in a number of comparative studies of group size. The relationship between neocortex and sociality is thought to exist either because relative neocortex size limits group size or because a larger group size selects for a larger neocortex. However, research on primate social evolution has indicated that male and female group sizes evolve in relation to different demands. While females mostly group according to conditions set by the environment, males instead simply go where the females are. Thus, any hypothesis relating to primate social evolution has to analyse its relationship with male and female group sizes separately. Since sex-specific neocortex sizes in primates are unavailable in sufficient quantity, I here instead present results from phylogenetic comparative analyses of unsexed relative neocortex sizes and female and male group sizes. These analyses show that while relative neocortex size is positively correlated with female group size, it is negatively, or not at all correlated with male group size. This indicates that the social intelligence hypothesis only applies to female sociality.

Animals↗

PubMed2006

Ranging patterns and parasitism in primates.

Competing hypotheses exist concerning the influence of ranging patterns on parasitism. More intensive use of a home range could result in greater exposure to infectious agents that accumulate in the soil. Alternatively, when more intensive ranging is associated with territorial defence, this could decrease home range overlap and produce lower levels of parasitism. We tested these hypotheses using phylogenetic comparative methods and parasite richness data for 119 primate species. Helminth richness increased with the defensibility index, a quantitative measure of home range use that correlates with the degree of territoriality in primates. This association was independent of other host traits that influence parasite richness in primates. Results involving non-vector transmitted helminths produced the most significant results, suggesting that the relationship between territorial behaviour and parasitism is driven by accumulation of parasites in defended home ranges. In addition, costs associated with greater ranging could increase susceptibility to infectious agents.

Animals↗

PubMed1996

Neocortex size and behavioural ecology in primates.

The neocortex is widely held to have been the focus of mammalian brain evolution, but what selection pressures explain the observed diversity in its size and structure? Among primates, comparative studies suggest that neocortical evolution is related to the cognitive demands of sociality, and here I confirm that neocortex size and social group size are positively correlated once phylogenetic associations and overall brain size are taken into account. This association holds within haplorhine but not strepsirhine primates. In addition, the neocortex is larger in diurnal than in nocturnal primates, and among diurnal haplorhines its size is positively correlated with the degree of frugivory. These ecological correlates reflect the diverse sensory-cognitive functions of the neocortex.

Animals↗

PubMed1998

Visual specialization and brain evolution in primates.

Several theories have been proposed to explain the evolution of species differences in brain size, but no consensus has emerged. One unresolved question is whether brain size differences are a result of neural specializations or of biological constraints affecting the whole brain. Here I show that, among primates, brain size variation is associated with visual specialization. Primates with large brains for their body size have relatively expanded visual brain areas, including the primary visual cortex and lateral geniculate nucleus. Within the visual system, it is, in particular, one functionally specialized pathway upon which selection has acted: evolutionary changes in the number of neurons in parvocellular, but not magnocellular, layers of the lateral geniculate nucleus are correlated with changes in both brain size and ecological variables (diet and social group size). Given the known functions of the parvocellular pathway, these results suggest that the relatively large brains of frugivorous species are products of selection on the ability to perceive and select fruits using specific visual cues such as colour. The separate correlation between group size and visual brain evolution, on the other hand, may indicate the visual basis of social information processing in the primate brain.

Animals↗

PubMed2005

The social nature of primate cognition.

The hypothesis that the enlarged brain size of the primates was selected for by social, rather than purely ecological, factors has been strongly influential in studies of primate cognition and behaviour over the past two decades. However, the Machiavellian intelligence hypothesis, also known as the social brain hypothesis, tends to emphasize certain traits and behaviours, like exploitation and deception, at the expense of others, such as tolerance and behavioural coordination, and therefore presents only one view of how social life may shape cognition. This review outlines work from other relevant disciplines, including evolutionary economics, cognitive science and neurophysiology, to illustrate how these can be used to build a more general theoretical framework, incorporating notions of embodied and distributed cognition, in which to situate questions concerning the evolution of primate social cognition.

Animals↗

PubMed1999

Phylogenetic analysis of GB viruses A and C: evidence for cospeciation between virus isolates and their primate hosts.

GB viruses A and C (GBV-A and GBV-C) have been isolated from humans and non-human primates. Phylogenetic analysis based on full-length polyproteins suggests that these two viruses have a common ancestor. It has now been determined that analysis of subgenomic amino acid sequences in the E2 and NS5 regions of GBV-A and a 345 nucleotide segment in the 5' non-coding (5'NC) region was able to reproduce the phylogenetic relationships obtained by complete polyprotein sequences analysis. Using 5'NC sequences from databases, GBV-A isolates were discriminated into eight genetic groups, each one closely associated with specific primate hosts. Phylogenetic analyses performed on sequences from the epsilon-globin genes of primate hosts on one hand and complete polyprotein sequences from GBV-A and GBV-C isolates on the other suggest that a mechanism of cospeciation could be involved in virus evolution over a period of 35 million years.

Animals↗

PubMed2002

Genomic characterization of TT viruses (TTVs) in pigs, cats and dogs and their relatedness with species-specific TTVs in primates and tupaias.

Using PCR with primers derived from a non-coding region of the human TT virus (TTV) genome, the TTV sequence in serum samples obtained from pigs (Sus domesticus), dogs (Canis familiaris) and cats (Felis catus) was identified and the entire genomic sequence was determined for each representative isolate. Three TTV isolates (Sd-TTV31 from a pig, Cf-TTV10 from a dog and Fc-TTV4 from a cat) comprising 2878, 2797 and 2064 nucleotides, respectively, each had three open reading frames (ORFs) encoding 436-635 (ORF1), 73-105 (ORF2) and 224-243 (ORF3) aa but lacked ORF4, similar to tupaia TTV. ORF3 was presumed to arise from a splicing of TTV mRNA, similar to human prototype TTV. Although the nucleotide sequence of Sd-TTV31, Cf-TTV10 and Fc-TTV4 differed by more than 50% from each other and from previously reported TTVs of 3.4-3.9 kb and TTV-like mini viruses (TLMVs) of 2.8-3.0 kb isolated from humans and non-human primates as well as tupaia TTVs of 2.2 kb, they resembled known TTVs and TLMVs with regard to genomic organization and presumed transcriptional profile rather than animal circoviruses of 1.7-2.3 kb. Phylogenetic analysis revealed that Sd-TTV31, Cf-TTV10 and Fc-TTV4 were closer to TTVs from lower-order primates and tupaias than to TTVs from higher-order primates and TLMVs. These results indicate that domestic pigs, cats and dogs are naturally infected with species-specific TTVs with small genomic size and suggest a wide distribution of TTVs with extremely divergent genomic sequence and length in animals.

Animals↗

PubMed2004

Interactions of decay-accelerating factor (DAF) with haemagglutinating human enteroviruses: utilizing variation in primate DAF to map virus binding sites.

A cellular receptor for the haemagglutinating enteroviruses (HEV), and the protein that mediates haemagglutination, is the membrane complement regulatory protein decay accelerating factor (DAF; CD55). Although primate DAF is highly conserved, significant differences exist to enable cell lines derived from primates to be utilized for the characterization of the DAF binding phenotype of human enteroviruses. Thus, several distinct DAF-binding phenotypes of a selection of HEVs (viz. coxsackievirus A21 and echoviruses 6, 7, 11-13, 29) were identified from binding and infection assays using a panel of primate cells derived from human, orang-utan, African Green monkey and baboon tissues. These studies complement our recent determination of the crystal structure of SCR(34) of human DAF [Williams, P., Chaudhry, Y., Goodfellow, I. G., Billington, J., Powell, R., Spiller, O. B., Evans, D. J. & Lea, S. (2003). J Biol Chem 278, 10691-10696] and have enabled us to better map the regions of DAF with which enteroviruses interact and, in certain cases, predict specific virus-receptor contacts.

Amino Acid Sequence↗

PubMed2005

Evolution of base-substitution gradients in primate mitochondrial genomes.

Inferences of phylogenies and dates of divergence rely on accurate modeling of evolutionary processes; they may be confounded by variation in substitution rates among sites and changes in evolutionary processes over time. In vertebrate mitochondrial genomes, substitution rates are affected by a gradient along the genome of the time spent being single-stranded during replication, and different types of substitutions respond differently to this gradient. The gradient is controlled by biological factors including the rate of replication and functionality of repair mechanisms; little is known, however, about the consistency of the gradient over evolutionary time, or about how evolution of this gradient might affect phylogenetic analysis. Here, we evaluate the evolution of response to this gradient in complete primate mitochondrial genomes, focusing particularly on A-->G substitutions, which increase linearly with the gradient. We developed a methodology to evaluate the posterior probability densities of the response parameter space, and used likelihood ratio tests and mixture models with different numbers of classes to determine whether groups of genomes have evolved in a similar fashion. Substitution gradients usually evolve slowly in primates, but there have been at least two large evolutionary jumps: on the lineage leading to the great apes, and a convergent change on the lineage leading to baboons (Papio). There have also been possible convergences at deeper taxonomic levels, and different types of substitutions appear to evolve independently. The placements of the tarsier and the tree shrew within and in relation to primates may be incorrect because of convergence in these factors.

Animals↗

PubMed2005

Molecular evolution and tempo of amplification of human LINE-1 retrotransposons since the origin of primates.

We investigated the evolution of the families of LINE-1 (L1) retrotransposons that have amplified in the human lineage since the origin of primates. We identified two phases in the evolution of L1. From approximately 70 million years ago (Mya) until approximately 40 Mya, three distinct L1 lineages were simultaneously active in the genome of ancestral primates. In contrast, during the last 40 million years (Myr), i.e., during the evolution of anthropoid primates, a single lineage of families has evolved and amplified. We found that novel (i.e., unrelated) regulatory regions (5'UTR) have been frequently recruited during the evolution of L1, whereas the two open-reading frames (ORF1 and ORF2) have remained relatively conserved. We found that L1 families coexisted and formed independently evolving L1 lineages only when they had different 5'UTRs. We propose that L1 families with different 5'UTR can coexist because they don't rely on the same host-encoded factors for their transcription and therefore do not compete with each other. The most prolific L1 families (families L1PA8 to L1PA3) amplified between 40 and 12 Mya. This period of high activity corresponds to an episode of adaptive evolution in a segment of ORF1. The correlation between the high activity of L1 families and adaptive evolution could result from the coevolution of L1 and a host-encoded repressor of L1 activity.

5' Untranslated Regions↗

PubMedDate not supplied

Properties of LTP induction in the CA3 region of the primate hippocampus.

Activity-dependent changes in synaptic strength, such as long-term potentiation (LTP), have been proposed to underlie memory storage in the brains of all mammals, including humans. However, most forms of synaptic plasticity, including LTP, are studied almost exclusively in rodents and related species. Thus, the hypothesis that LTP is important in human memory relies on the assumption that LTP is similar in the primate and rodent brains. We have begun to test this hypothesis by studying the properties and mechanisms of LTP induction in area CA3 of hippocampal slices from cynomolgus monkeys. We have found that LTP can be induced reliably at both mossy fiber-CA3 and collateral/associational-CA3 synapses in the primate brain, and that the properties of LTP induction at these synapses are similar to what we and others have observed in experiments using hippocampal slices from rodents. Also, we have investigated the role of opioids in mossy fiber synaptic transmission and LTP and have found no effect of the opioid antagonist naloxone nor the opioid agonist dynorphin on mossy fiber synaptic transmission or potentiation. These data suggest that LTP in the primate and rat brains has a similar induction mechanism and, thus, that the rodent is a useful animal model in which to study synaptic modification such as LTP.

Animals↗

PubMed2004

Anti-pig antibody levels in non-human primates of various origin.

BACKGROUND: Natural anti-porcine antibodies play a major role in hyperacute solid organ xenograft rejection in the pig-to-non-human primate model. Work from other groups and our experience in transplantation experiments has shown that antibody levels are highly variable between non-human primate species, and that extremely high levels can mediate hyperacute rejection even if organs from animals transgenic for human decay-accelerating factor are used. METHODS: Sera were obtained from cynomolgus monkeys wild-caught in Mauritius, captive-bred in the Philippines, captive-bred in Indonesia (Indonesia-Ind), and originating from Indonesia but colony-bred in USA (Indonesia-USA), from baboons wild-caught in Kenya, and from rhesus monkeys originating from India but colony-bred in USA (10 animals in each group). Antibody levels were determined using assays for haemolytic antibody (APA), IgM and IgG class anti-Galalpha1-3Gal antibody, and IgM and IgG class anti-endothelial cell antibody. RESULTS: Cynomolgus monkeys from the Philippines and Indonesia-USA and rhesus monkeys showed median APA and IgM antibody levels in the same range as a pooled human serum standard, and median IgG levels well below the level in this standard. Cynomolgus monkeys from Mauritius and Indonesia-Ind showed extremely high APA levels (median seven to 10 times the human serum standard): IgM class antibodies were also higher, while IgG class antibodies were in the range of the level in the human serum standard. Antibody levels in baboons were in between these two categories. The results of the APA assay showed a highly statistically significant correlation with the assays of IgM antibody, and this was also the case for the IgM antibody assays, indicative of the assessment of the same antibodies in these assays. The same was observed for the assays for IgG antibody. Taking body weight as an indicator for age, there was no relationship between body weight and levels of antibodies. CONCLUSIONS: Natural antibody levels show a significant variation between various groups of non-human primates, with levels in some groups well above those in a human serum standard.

Animals↗