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Selection on human genes as revealed by comparisons to chimpanzee cDNA.

To better understand the evolutionary forces that affect human genes, we sequenced 5055 expressed sequence tags from the chimpanzee and compared them to their human counterparts. In conjunction with intergenic chimpanzee DNA sequences and data on human single-nucleotide polymorphisms in the genes studied, this allows us to gauge the extent to which selection affects human genes at a genome-wide scale. The comparison to intergenic DNA sequences indicates that about 39% of silent sites in protein-coding regions are deleterious and subject to negative selection. Further, when the divergence between human and chimpanzee is compared with the extent of nucleotide polymorphisms among humans in the same sequences, there is significantly higher divergence in the 5' untranslated regions (UTRs) but not in other parts of the transcript. This indicates that positive selection may have had a considerable influence on 5'UTRs. The dinucleotide CG (CpG) also exhibits a different substitution pattern within 5'UTRs as compared with other parts of the genome.

Amino Acid Substitution↗

Chimpanzees (Pan troglodytes) recognize spatial and object correspondences between a scale model and its referent.

In the present study, the contributions of spatial and object features to chimpanzees' comprehension of scale models were examined. Seven chimpanzees that previously demonstrated the ability to use a scale model as an information source for the location of a hidden item were tested under conditions manipulating the feature correspondence and spatial-relational correspondence between objects in the model and an outdoor enclosure. In Experiment 1, subjects solved the task under two conditions in which one object cue (color or shape) was unavailable, but positional cues remained. Additionally, performance was above chance under a third condition in which both types of object cues, but not position cues, were available. In Experiment 2, 2 subjects solved the task under a condition in which shape and color object cues were simultaneously unavailable. The results suggest that, much like young children, chimpanzees are sensitive to both object and spatial-relational correspondences between a model and its referent.

Animals↗

Paternity exclusion in a community of wild chimpanzees using hypervariable simple sequence repeats.

We report the use of hypervariable simple sequence repeat (SSR) nuclear loci to study paternity in a community of wild chimpanzees (Pan troglodytes schweinfurthii) in Gombe National Park, Tanzania. All 43 living members of a habituated community were sampled and 35 were genotyped at 8 SSR loci using DNA amplified from hair. Paternity exclusions were performed for 25 chimpanzees including 10 for whom the mother was also genotyped. In each case 12-20 males were potential fathers based on their age and/or direct observation of sexual behaviour. 179 tests involving potential father/offspring combinations were performed. In four cases the data permit the probable identification of the previously undetermined father; these are the first such determinations for free-ranging chimpanzees, and the first based on non-invasive sampling. In another four cases we were able to exclude all but two to five potential fathers, and in the remaining cases we were able to exclude all living males. For molecular ecologists SSR genotype databases offer important advantages over currently popular minisatellite DNA finger-printing: they can be analysed unequivocally using traditional population genetics techniques and they can be expanded through time and space by other researchers.

Alleles↗

Mixed lymphocyte reactivity in chimpanzees. I. Some technical and genetic aspects.

One-way mixed lymphocyte culture (MLC) tests were performed among the members of five chimpanzee harems in all possible combinations: parents, parent-child, siblings and half-siblings. The technical aspects of MCL testing in chimpanzees appeared to be very similar to those observed for human and rhesus monkey MLC's. Two unexpected observations were made for which no satisfactory explanation can as yet be give: firstly, the occurrence of animals with consistently high autologous values and secondly, the existence of chimpanzees displaying low MLC responsive. The high autologous values occurred mostly in older imported animals (25% with high autologous values), while only one of the 45 laboratory born animals showed this phenomenon. Low responsiveness occurred in a few offspring belonging to a single harem only and is therefore likely to be genetically controlled but, as it appeared, not by genes linked to ChLA. Data suggesting the existence of an MHC-linked "major MLC" or D locus were confirmed and extended. A gene dose effect for D locus antigens was demonstratable, i.e., combinations of related animals differing for one showed lower MLC responses than combinations differing for two ChLA haplotypes. The number of D locus alleles was estimated to be 10.

Animals↗

Posaconazole therapy for systemic coccidioidomycosis in a chimpanzee (Pan troglodytes): a case report.

Systemic coccidioidomycosis was diagnosed in a 4-year-old male chimpanzee (Pan troglodytes) with ascites and failure to thrive. Physical examination, laboratory and radiological studies, and exploratory laparotomy showed signs of systemic fungal infection that included penetration into the central nervous system (CNS). Serum and cerebrospinal fluid (CSF) titres, along with ascites cytology findings, confirmed the presence of Coccidioides immitis. However, the organism could not be cultured from the CSF. Treatment with fluconazole 10 mg kg(-1) daily for 6 months was not associated with clinical improvement. Subsequent treatment with posaconazole 50 mg kg(-1) daily for approximately 24 months resulted in negative serum titres and improved clinical status. Illness not directly related to the C. immitis infection caused the chimpanzee's deterioration and eventual killing. Histological examination performed during necropsy provided no evidence of coccidioidomycosis; however, a positive C. immitis serum antibody titre was noted. The successful suppression of coccidioidomycosis observed in this chimpanzee suggests that posaconazole may have a role in the treatment of CNS infections caused by susceptible fungi.

Animals↗

Can chimpanzee infants (Pan troglodytes) form categorical representations in the same manner as human infants (Homo sapiens)?

We directly compared chimpanzee infants and human infants for categorical representations of three global-like categories (mammals, furniture and vehicles), using the familiarization-novelty preference technique. Neither species received any training during the experiments. We used the time that participants spent looking at the stimulus object while touching it as a measure. During the familiarization phase, participants were presented with four familiarization objects from one of three categories (e.g. mammals). Then, they were tested with a pair of novel objects, one was a familiar-category object and another was a novel-category object (e.g. vehicle) in the test phase. The chimpanzee infants did not show significant habituation, whereas human infants did. However, most important, both species showed significant novelty-preference in the test phase. This indicates that not only human infants, but also chimpanzee infants formed categorical representations of a global-like level. Implications for the shared origins and species-specificity of categorization abilities, and the cognitive operations underlying categorization, are discussed.

Age Factors↗

Cooperative activities in young children and chimpanzees.

Human children 18-24 months of age and 3 young chimpanzees interacted in 4 cooperative activities with a human adult partner. The human children successfully participated in cooperative problem-solving activities and social games, whereas the chimpanzees were uninterested in the social games. As an experimental manipulation, in each task the adult partner stopped participating at a specific point during the activity. All children produced at least one communicative attempt to reengage him, perhaps suggesting that they were trying to reinstate a shared goal. No chimpanzee ever made any communicative attempt to reengage the partner. These results are interpreted as evidence for a uniquely human form of cooperative activity involving shared intentionality that emerges in the second year of life.

Adult↗

Chimpanzee lipoprotein(A): Relationship between apolipoprotein(A) isoform size and the density profile of lipoprotein(A) in animals with different heterozygous apo(A) phenotypes.

In a previous study [C. Doucet et al., J. Lipid Res 35:263-270, 1994], we have shown that plasma lipoprotein (a) [Lp(a)] levels were significantly elevated in a population of unrelated chimpanzees as compared to those in normolipidemic human subjects. Nonetheless, the inverse correlation between Lp(a) levels and apolipoprotein (a) [apo(a)] isoforms typical of man was maintained in the chimpanzee. In the present study, we describe the density profiles of apo B- and apo A1-containing lipoproteins and of Lp(a) in chimpanzee plasmas heterozygous for apo(a) isoforms after fractionation by single spin ultracentrifugation in an isopycnic gradient. The distribution of apo(a) isoforms in the density gradient was also examined by SDS-agarose gel electrophoresis and immunoblotting using chemiluminescence detection. In all double-band phenotypes examined, the smallest isoform was present along the entire length of the density gradient. The density distribution of the second isoform varied according to the size difference between the respective isoforms. Two isoforms close in size (difference in apparent molecular mass = 60 kDa) were present together in every gradient subfraction. On the contrary, when the two isoforms displayed distinct molecular mass (maximal difference in apparent molecular mass = 340 kDa), then the largest was principally present in the densest fractions of the gradient (d > 1.1 mg/ml). These observations suggest that Lp(a) particles with small apo(a) isoforms are more susceptible to interact with other lipoproteins than are Lp(a) particles with large isoforms.

Animals↗

Treatment of myocardial dysfunction and pulmonary oedema in an infant chimpanzee.

The care of any critically ill infant requires special technical equipment for monitoring of cardiac and pulmonary functions including mechanical ventilators and blood gas analysers. The present paper describes the treatment of myocardial dysfunction and pulmonary distress, complicated by severe brain oedema in an infant chimpanzee admitted to an intensive care unit in the Department of Neonatology of the Children's Hospital of the University of Leipzig. The condition of the chimpanzee was diagnosed and monitored by standard clinical tooös including radiography, echocardiography, cerebral Doppler sonography and laboratory parameters. The chimpanzee was treated in close cooperation between veterinarians and paediatricians.

Animals↗

A papillomavirus related to HPV type 13 in oral focal epithelial hyperplasia in the pygmy chimpanzee.

An epizootic of focal epithelial hyperplasia (FEH) or Morbus Heck in a pygmy chimpanzee (Pan paniscus) colony is described. Papovavirus-like particles were observed in the nuclei of epithelial cells. Analysis of the DNA of the lesions revealed an episomal papillomavirus-specific band with a molecular size of approximately 8,000 bp. In situ hybridization under high stringency conditions showed cross-hybridization between the chimpanzee papillomavirus DNA and human papillomavirus (HPV) type 13. The latter virus is uniquely associated with oral disease in man. This is the first demonstration of the association of a HPV 13-related pygmy chimpanzee papillomavirus (PCPV) and oral epithelial hyperplasia in a nonhuman primate.

Animal Diseases↗

Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees.

The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.

Adult↗

The influence of dominance rank on the reproductive success of female chimpanzees.

Female chimpanzees often forage alone and do not display obvious linear dominance hierarchies; consequently, it has been suggested that dominance is not of great importance to them. However, with the use of data from a 35-year field study of chimpanzees, high-ranking females were shown to have significantly higher infant survival, faster maturing daughters, and more rapid production of young. Given the foraging behavior of chimpanzees, high rank probably influences reproductive success by helping females establish and maintain access to good foraging areas rather than by sparing them stress from aggression.

Animals↗

Asymmetry of chimpanzee planum temporale: humanlike pattern of Wernicke's brain language area homolog.

The anatomic pattern and left hemisphere size predominance of the planum temporale, a language area of the human brain, are also present in chimpanzees (Pan troglodytes). The left planum temporale was significantly larger in 94 percent (17 of 18) of chimpanzee brains examined. It is widely accepted that the planum temporale is a key component of Wernicke's receptive language area, which is also implicated in human communication-related disorders such as schizophrenia and in normal variations such as musical talent. However, anatomic hemispheric asymmetry of this cerebrocortical site is clearly not unique to humans, as is currently thought. The evolutionary origin of human language may have been founded on this basal anatomic substrate, which was already lateralized to the left hemisphere in the common ancestor of chimpanzees and humans 8 million years ago.

Animals↗

Antiviral activity of a bis-benzimidazole against experimental rhinovirus infections in chimpanzees.

The marked antiviral activity of (S,S-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethanediol (Abbott 36683) against rhinoviruses in tissue culture warranted investigation of its antiviral activity in vivo. Antiviral levels in mouse sera were attained with an oral dose as small as 10 mg/kg and detectable antiviral levels of drug were also found in lung, liver, kidney, intestinal contents, and urine of mice given a single 300 mg/kg oral dose. Antiviral serum levels were also obtained when monkeys were given a single oral dose of Abbott 36683. Six chimpanzees were infected with 100 median tissue culture infective dose units (TCID(50)) of rhinovirus 30. Three of the animals were treated with Abbott 36683, 100 mg/kg daily for 4 consecutive days. Virus shedding occurred in the infected controls but could not be demonstrated in the treated animals from postinfection days 1 to 8. Two of the treated animals did, however, shed virus on day 9. The compound was retested in chimpanzees at dosage levels of 15 and 50 mg/kg daily for 4 days. Each animal was challenged with 100 TCID(50) of rhinovirus 49. Partial protection was obtained. In a third trial, a single 100 mg/kg dose of the compound was administered to chimpanzees infected with rhinovirus 44. Virus was isolated from all throat smears taken from treated animals, indicating that at the lowest drug level no protection occurred.

Administration, Oral↗

Isolation and characterization of a chimpanzee monoclonal antibody to the G glycoprotein of human respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract disease in infants and young children. In this study a hybridoma line secreting a chimpanzee monoclonal antibody that neutralizes RSV was isolated. Two chimpanzees were immunized with recombinant vaccinia viruses that express the RSV F or G surface glycoprotein and 1 month later were infected intranasally with the wild-type RSV strain A2. Peripheral blood lymphocytes obtained from the animals were transformed with Epstein-Barr virus, and lymphoblastoid cell lines that secreted anti-RSV antibodies were identified by an RSV antigen-binding enzyme-linked immunosorbent assay. Supernatants from RSV antibody-secreting lymphoblastoid cell lines were tested for in vitro virus neutralization before being fused to the heteromyeloma cell GLI-H7. A chimpanzee antibody [immunoglobulin G3(lambda) subclass] produced from a hybridoma line designated E1.4/2 was shown to bind to the RSV G glycoprotein and neutralize a panel of subgroup A viruses, but not subgroup B viruses, at low (nanomolar) concentrations. Mice passively immunized with this antibody were partially resistant to RSV strain A2 challenge. The usefulness of such antibodies in immunoprophylaxis and immunotherapy of RSV infection is discussed.

Animals↗

Transmission of hepatitis B to chimpanzees by hepatitis B surface antigen-positive saliva and semen.

To assess the infectivity of hepatitis B surface antigen (HBsAg)-containing body fluids other than blood, chimpanzees were inoculated intravenously with saliva and semen obtained from HBsAg-positive individuals implicated in non-percutaneous transmission of hepatitis B. Saliva and semen samples were negative for occult blood. The titer of HBsAg in saliva was on the average only 1/3,000 that of the corresponding serum. One chimpanzee, inoculated sequentially with saliva from three individuals, developed HBsAg at 9 weeks and serum glutamic pyruvic transaminase elevation at 13 weeks after injection. HBsAg persisted for 15 weeks. This animal also developed e antigen, anti-core antibody, and anti-surface antibody. Liver biopsies showed acute hepatitis that subsequently resolved. A second chimpanzee, inoculated with HBsAg-positive semen, developed HBsAg and elevated serum glutamic pyruvic transaminase 4 weeks after inoculation and then died suddenly without explanation. HBsAg was positive in two consecutive samples and was confirmed by specific neutralization. Autopsy did not reveal evidence of hepatitis. This study demonstrates that HBsAg-positive saliva and, probably, semen contain infectious virus and suggests that saliva and/or semen may serve as important mechanisms in the transmission of type B hepatitis.

Animals↗

Detection of the hepatitis C virus genome in acute and chronic experimental infection in chimpanzees.

In order to gain an understanding of the relationship of various markers of hepatitis C virus (HCV) infection in acute and chronic cases of the disease, serial blood samples obtained from chimpanzees before and after infection with HCV were analyzed for the presence of the HCV genome by using polymerase chain reaction (PCR) amplification of cDNA (cDNA PCR) synthesized from plasma- and serum-derived RNA. In a chimpanzee with acute hepatitis C, signals detectable by cDNA PCR appeared 1 week before characteristic ultrastructural changes visualized by electron microscopy, persisted throughout the peak alanine aminotransferase levels, and diminished with the disappearance of alterations visualized by electron microscopy. This was in contrast to the results obtained from chimpanzees with chronic HCV infection, in which the HCV genome was consistently detectable for up to 10 years after infection. The results indicate the usefulness of detection of HCV RNA by cDNA PCR as a sensitive and semiquantitative method for monitoring the course of HCV infection and as a potential marker for differentiating between chronic and acute cases of disease.

Acute Disease↗

Transmission of simian immunodeficiency virus SIVcpz and the evolution of infection in the presence and absence of concurrent human immunodeficiency virus type 1 infection in chimpanzees.

Current data suggest that the human immunodeficiency virus type 1 (HIV-1) epidemic arose by transmission of simian immunodeficiency virus (SIV) SIVcpz from a subspecies of common chimpanzees (Pan troglodytes troglodytes) to humans. SIVcpz of chimpanzees is itself a molecular chimera of SIVs from two or more different monkey species, suggesting that recombination was made possible by coinfection of one individual animal with different lentiviruses. However, very little is known about SIVcpz transmission and the susceptibility to lentivirus coinfection of its natural host, the chimpanzee. Here, it is revealed that either infected plasma or peripheral blood mononuclear cells readily confer infection when exposure occurs by the intravenous or mucosal route. Importantly, the presence of preexisting HIV-1 infection did not modify the kinetics of SIVcpz infection once it was established by different routes. Although humoral responses appeared as early as 4 weeks postinfection, neutralization to SIVcpz-ANT varied markedly between animals. Analysis of the SIVcpz env sequence over time revealed the emergence of genetic viral variants and persistent SIVcpz RNA levels of between 10(4) and 10(5) copies/ml plasma regardless of the presence or absence of concurrent HIV-1 infection. These unique data provide important insight into possible routes of transmission, the kinetics of acute SIVcpz infection, and how readily coinfection with SIVcpz and other lentiviruses may be established as necessary preconditions for potential recombination.

Animals↗