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The angular distribution of vertebral trabeculae in modern humans, chimpanzees and the Kebara 2 Neanderthal.

Bone is known to remodel to optimize its structure according to its mechanical environment. In particular trabecular arcades are thought to align with the orientations of components of principal strain. This paper presents the application of a novel method for quantifying trabecular orientation to test the hypothesis that hominoid posture and locomotion are reflected in trabecular architecture. Lateral radiographs were taken of vertebrae from the entire thoracolumbar spines of eight modern humans, seven Pan troglodytes and one Neanderthal. The radiographs were digitized and a square region of interest located at the centre of each vertebral body selected. Fourier transforms of the regions of interest were performed and the relative magnitude of the transform in each of 16 angular segments calculated. The simple indices of external vertebral body morphology, wedge angle and aspect ratio, were also calculated from the radiographs. All three species exhibit the same pattern, with the majority of trabeculae oriented either axially or dorsoventrally. This suggests that vertebral mechanical loading is similar in chimpanzees and humans, despite their apparent postural and locomotor differences. Significant differences between the magnitudes of the Fourier transform in the 78.75 degrees and 135 degrees orientations of chimpanzee and human vertebrae were observed in all but the upper thoracic spine. As the magnitudes at these orientations in the Neanderthal correspond more closely to that in the human and the orientational features were unrelated to the external vertebral morphology, the difference between the two magnitudes may well prove to be a useful parameter in future phylogenetic analysis. Modern human spines were found to show a greater variation in the proportions of axial and dorsoventral trabeculae with spinal level than chimpanzees, with the greatest differences observed in the upper thoracic spine and thoracolumbar junction, suggesting an association with postural spinal curves.

Animals↗

Premature stop codons inactivate the RT6 genes of the human and chimpanzee species.

RT6 is a glycosyl phosphatidylinositol-anchored cell membrane protein, whose expression is restricted to peripheral T cells and intraepithelial lymphocytes. It has attracted interest as a T cell differentiation marker and activation antigen in rats. The only known protein to which RT6 shows significant homology is a recently cloned mono(ADP-ribosyl)transferase of rabbit skeletal muscle which is distantly related also to certain bacterial toxins. Intriguingly, whereas the rat carries a single copy RT6 gene with two known highly divergent alleles, the mouse carries two closely linked, functional RT6 genes that show approximately 85% sequence identity. We have now cloned and sequenced the homologues of the RT6 genes from humans of distinct ethnic backgrounds and of the chimpanzee. Surprisingly, in each case, three premature in-frame stop codons preclude expression of the single copy RT6 gene as a cell surface protein. Otherwise, the RT6 genes of human and chimpanzee exhibit high structural conservation to their rodent counterparts. RNA expression analyses indicate that the RT6 gene is not transcriptionally active in human T cells or any other human tissue analyzed so far. To our knowledge, RT6 represents the first mammalian membrane protein identified that has been lost universally in the human and chimpanzee species due to gene inactivation.

ADP Ribose Transferases↗

Experimentally induced Mycoplasma pneumoniae pneumonia in chimpanzees.

Eight chimpanzees were examined. Two served as negative control and six inoculated with Mycoplasma pneumoniae became colonized. Colonization persisted for 28-68, 16-50 and 21 days with an average duration of 47, 32.5 and 21 days in the oropharyngeal, tracheal and lung tissues, respectively. Mycoplasma titers ranged from 10(8) to 10(1) color-changing units per specimen during the course of the infections. Seroconversion occurred within 12-15 days and peak antibody titers ranged from 1.256 to 1.1024 and developed between days 28 and 48 post-inoculation. Positive cold agglutinin titers were detected between 12 to 15 days and peak titers ranged from 1:80 to 1:640. Significant increases in sIgA and IgG immunoglobulin antibody levels were detected in lung lavage fluids. Unlike the many other experimentally infected animals examined, chimpanzees infected with M. pneumoniae had positive X-ray findings, developed cold agglutinins and showed overt signs of disease. These signs include persistent cough, low grade fever, rhinitis, oropharyngitis, diarrhea, and loss of appetite. Peak severity of disease corresponded with peak lung colonization, and the detection of cold agglutinins and positive X-ray findings. The microbiological, serological and clinical aspects of pneumonia induced in chimpanzees was similar to naturally occurring primary atypical pneumonia in humans.

Agglutinins↗

Demonstration of in vitro infection of chimpanzee hepatocytes with hepatitis C virus using strand-specific RT/PCR.

Analysis of hepatitis C virus (HCV) replication has been hampered due to the difficulty encountered in in vitro cultivation of the virus in conventional tissue culture systems. In this study, primary chimpanzee hepatocyte cultures maintained in a serum-free medium formulation were susceptible to in vitro infection with HCV. In order to document infection, two new methods of reverse transcription/polymerase chain reaction were developed that permit accurate distinction between positive and negative strand HCV RNA. One method relied upon the use of a tagged cDNA primer, while the second method employed a thermostable reverse transcriptase. Following inoculation of chimpanzee hepatocytes with HCV, intracellular positive and negative strand HCV RNA were detectable 4 days postinfection and throughout the remainder of the experimental period, 25 days. Analysis of HCV-inoculated baboon hepatocytes revealed a total absence of negative strand HCV RNA, while residual positive strand RNA from the inoculum could be detected for up to 11 days. The in vitro replication of HCV RNA in chimpanzee hepatocytes could be suppressed by alpha-interferon. This system should be amenable to the study of HCV replication, antiviral compounds, and the development of neutralization assays.

Animals↗

Four chimpanzee monoclonal antibodies isolated by phage display neutralize hepatitis a virus.

Chimpanzee immunoglobulins are virtually identical to human immunoglobulins and may have clinically useful applications. Four chimpanzee monoclonal antibodies (MAbs) to the hepatitis A virus (HAV) capsid were isolated from a combinatorial cDNA library of gamma1/kappa antibody genes using phage display. Competition assays indicated that three of the MAbs recognized the same or overlapping epitopes, whereas the fourth recognized a different, nonoverlapping epitope on the HAV capsid. All four MAbs neutralized the homologous HAV strain, HM-175, in a radioimmunofocus assay and two of the four MAbs neutralized a heterologous simian HAV strain, AGM-27. From these data, we conclude that the MAbs must recognize at least three epitopes on the HAV capsid. Furthermore, competition assays performed with neutralizing murine MAbs suggested that three of the chimpanzee MAbs recognized epitopes on the HAV capsid which have not been defined previously.

Amino Acid Sequence↗

Differentiation between human and chimpanzee in bloodstains by enzyme-linked immunosorbent assay (ELISA) using antihuman serum.

An enzyme-linked immunosorbent assay (ELISA) for species identification of human bloodstains using two commercially available antisera against human serum is described. Human bloodstains were to be distinguished from those of chimpanzees and other animals using raw antisera, and the differentiation between human and chimpanzee became more evident when those antisera were absorbed with a small amount of chimpanzee plasma. Human bloodstains could clearly be identified by the present method even after 4 weeks of aging at room temperature.

Animals↗

The distribution of sequences complementary to human satellite DNAs I, II and IV in the chromosomes of chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orang utan (Pongo pygmaeus).

Human satellite DNAs I, II and IV were transcribed to yield radioactive complementary RNAs (cRNAs). These cRNAs were hybridised to metaphase chromosomes of man, chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orang utan (Pongo pygmaeus). The results of this in situ hybridisation were analysed quantitatively and compared with accepted chromosome homologies based on Giemsa banding patterns. The cRNA to satellite II (cRNAII) did not hybridise to chimpanzee chromosomes, although its hybridisation to chromosomes of gorilla and orang utan yielded more autoradiograph grains than hybridisation to human chromosomes, and cRNAIV hybridised to many chromosomes of gorilla and chimpanzee but was almost entirely restricted to the Y chromosome in orang utan. Most sites of hybridisation were located on homologous chromosomes in all four species, but there were a number of sites which showed no correspondence between satellite DNA location and chromosome banding patterns, and others where a given chromosomal location hybridised with different cRNAs in each species. These results are in contrast to those found for many transcribed DNA sequences, where the same sequence is usually located at homologous chromosome sites in different species, and appear to cast doubt on many proposed models of satellite DNA function.

Animals↗

There are two C4 genetic loci and a null allele in the chimpanzee.

Genetic polymorphism in C4 in the chimpanzee was studied by agarose gel electrophoresis of desialated plasma and development of patterns by immunofixation with antiserum to human C4 and by a C4-sensitive hemolytic overlay. In general, immunofixation patterns showed multiple partially overlapping bands of which only the most cathodal had strong hemolytic activity. In analogy to human C4, the latter were designated C4B, whereas those detected by immunofixation which had little hemolytic activity were designated C4A. Chimp C4A and C4B reacted with human and mouse (monoclonal) anti-C4B and human anti-Ch1 but neither reacted with monoclonal anti-C4A or human anti-Ch2, Ch3, Rg1, or Rg2. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the alpha chain of C4B showed a slightly lower apparent relative mass than that of C4A at around Mr 93,000. There were three C4A variants and two C4B variants inherited in families as autosomal codominant traits, as C4A-C4B cosegregating pairs with no detectable crossing-over. These pairs were inherited with chimpanzee leukocyte antigen types C2 and BF variants without detectable crossing-over. Half-null C4 haplotypes with C4B QO were observed in family studies. Nine BF, C2, C4A, C4B allelic haplotypic combinations (complotypes) were identified among presumably unrelated chimpanzees.

Alleles↗

HLA-DR7-specific monoclonal antibodies and a chimpanzee anti-DR7 serum detect different epitopes on the same molecule.

We describe here two monoclonal antibodies with HLA-DR7 serologic specificity. The antibodies, SFR16-DR7M, a cytotoxic rat IgM antibody of high affinity, and SFR16-DR7G, a noncytotoxic antibody of the rat IgG 2a class, react with only DR7-positive cells in radioimmunoassay. The cytotoxic activity of SFR16-DR7M correlates completely with the presence of the DR7 specificity, and segregates with the DR7-bearing haplotype in a family. SFR16-DR7M precipitates a class II molecule with the electrophoretic characteristics of DR molecules from LG-10, an HLA-DR7 homozygous cell line. SFR16-DR7G completely inhibits the cytotoxicity of SFR16-DR7M, but only partially inhibits the cytotoxicity of a chimpanzee antiserum with DR7 specificity, Gay/Swei. In binding-inhibition studies, binding of SFR16-DR7M to LG-10 cells is only partially inhibited by the chimpanzee antiserum and vice versa. Both SFR16-DR7M and Gay/Swei reciprocally deplete the same class II molecules from a 35S-methionine-labeled detergent-solubilized membrane preparation of the LG-10 cell line. The chimpanzee serum Gay contains antibodies reactive with epitopes on separated DR7 beta chains, while both SFR16-DR7M and SFR16-DR7G bind only to DR7 alpha-beta complexes. These data suggest that at least two allogenic epitopes exist which result in the same serologic specificity, and that these epitopes differ in their requirement for alpha-beta complex formation.

Animals↗

The genomic synteny at DNA level between human and chimpanzee chromosomes.

The evolutionary relationship between human (Homo sapiens) and chimpanzee (Pan troglodytes) has been the subject of debate and scrutiny for over two decades. The close relationship established by numerous parameters may or may not reflect homology at the DNA level. The recent advent of a molecular method termed the chromosome in situ suppression hybridization (CISS)-technique has prompted us to explore the phylogenetic relationship at the DNA sequence level. Cross-hybridization data using human-derived whole chromosome paints (WCPs) suggests an apparent genomic synteny with chimpanzee chromosomes at the DNA level, thus providing a better understanding of an evolutionary relationship between humans and chimpanzees.

Animals↗

Non-A, non-B hepatitis: visualization of virus-like particles from chimpanzee and human sera.

Virus-like particles (VLP), morphologically similar to togavirus particles, were detected in the sera of chimpanzees and humans with chronic non-A, non-B (NANB) hepatitis. Particles resembling the virus were also found in the cytoplasm of hepatocytes obtained from NANB hepatitis infected chimpanzees. Furthermore, two chimpanzees inoculated with materials containing the VLP developed NANB hepatitis. These results strongly suggest that the VLP may be closely associated with the agent of NANB hepatitis.

Animals↗

Effects of an oral contraceptive on sexual behavior of chimpanzees (Pan troglodytes)

Behavioral and physiological effects of a combined oral contraceptive (OC) were studied in chimpanzees for comparative purposes related to (i) the ambiguity surrounding the effects of OCs on the sexuality of humans, (ii) the close biological relationship between chimpanzees and humans, especially with respect to endogenous sex hormones and sexual behavior, and (iii) the relatively greater behavioral sensitivity of the chimpanzee to changes in sex hormone levels such as those that accompany the use of OCs. Two different types of pair tests and detailed behavioral assessments were used to differentiate the hormonal effects of female behavior from social effects imposed by the male. Anogenital swelling and copulation were reduced during OC cycles, but the effect of the OC on copulation was directly related to the social and sexual relationship of the pair during natural cycles. The more compatible and more frequently copulating pairs in the natural cycles continued to copulate during the OC cycles, albeit at reduced rates, whereas the less compatible and less frequently copulating pairs ceased copulating altogether when the female received the OC. There was no independent effect of the OC on ejaculation per se. Both male and female sexual initiative were reduced in the OC cycles, but female responsiveness to male sexual solicitations and direct copulatory attempts were not affected. Data indicate that despite generally adverse effects of the OC on certain physiological and behavioral dimensions of sexuality, social factors ultimately determined the degree of response to the OC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The number of nucleotides required to determine the branching order of three species, with special reference to the human-chimpanzee-gorilla divergence.

A mathematical theory for computing the probabilities of various nucleotide configurations among related species is developed, and the probability of obtaining the correct tree (topology) from nucleotide sequence data is evaluated using models of evolutionary trees that are close to the tree of mitochondrial DNAs from human, chimpanzee, gorilla, orangutan, and gibbon. Special attention is given to the number of nucleotides required to resolve the branching order among the three most closely related organisms (human, chimpanzee, and gorilla). If the extent of DNA divergence is close to that obtained by Brown et al. for mitochondrial DNA and if sequence data are available only for the three most closely related organisms, the number of nucleotides (m*) required to obtain the correct tree with a probability of 95% is about 4700. If sequence data for two outgroup species (orangutan and gibbon) are available, m* becomes about 2600-2700 when the transformed distance, distance-Wagner, maximum parsimony, or compatibility method is used. In the unweighted pair-group method, m* is not affected by the availability of data from outgroup species. When these five different tree-making methods, as well as Fitch and Margoliash's method, are applied to the mitochondrial DNA data (1834 bp) obtained by Brown et al. and by Hixson and Brown, they all give the same phylogenetic tree, in which human and chimpanzee are most closely related. However, the trees considered here are "gene trees," and to obtain the correct "species tree," sequence data for several independent loci must be used.

Animals↗

New cases of inter-community infanticide by male chimpanzees at Ngogo, Kibale National Park, Uganda.

Infanticide by males has been recorded in four chimpanzee populations, including that in Kibale National Park, Uganda. Some infanticidal attacks occur during inter-community aggression. The sexual selection hypothesis does not easily explain these attacks because they may not directly increase male mating opportunities. However, females in the attackers' community may benefit by expanding their foraging ranges and thereby improving their reproductive success; thus infanticide may increase male reproductive success indirectly. We report two new cases of infanticide by male chimpanzees at Ngogo, Kibale National Park. Like two previous cases, these occurred during a boundary patrol and were almost certainly between-community infanticides. The patrolling males attacked despite the proximity of males from the victims' presumed community. This probably explains why, unlike the earlier cases, they did not completely cannibalize their victims. Such attacks seem to be relatively common at Ngogo and infanticide may be an important source of infant mortality in neighboring communities. Our observations cannot resolve questions about the sexual selection hypothesis. However, they are consistent with the range expansion hypothesis: the infanticides occurred during a period of frequent encounters between communities associated with a mast fruiting event, and Ngogo community members greatly increased their use of areas near the attack site during another mast fruiting event one year later. Our observations contribute to growing evidence that lethal intergroup aggression is a common characteristic of wild chimpanzee populations.

Aggression↗

Reduced polymorphism in the chimpanzee semen coagulating protein, semenogelin I.

The semen of many primate species coagulates into a mating plug believed to prevent the sperm of subsequent mating events from accessing the ova. The texture of the coagulum varies among species: from a semisoft mass in humans to a firm plug in chimpanzees. In humans, a component of the coagulum, semenogelin I, also inhibits sperm motility. We tested the hypothesis that polymorphism and divergence at semenogelin I differ among hominoid species with different mating systems. Sequence data for the semenogelin I locus were obtained from 12 humans, 10 chimpanzees, 7 gorillas, and 1 bonobo. Mitochondrial D-loop data were collected from a subset of individuals to assess levels of variation at an unlinked locus. HKA tests using D-loop sequence data revealed a significant reduction of polymorphism at semenogelin I in chimpanzees, consistent with predictions of a selective sweep at this locus. This result was supported by independent HKA tests using polymorphism data from a putatively neutral locus from the literature. Humans show a similar trend toward reduced polymorphism, although HKA tests were only marginally significant. Gorilla sequence data show evidence of functional loss at the semenogelin I locus, indicated by stop codons within the putative open reading frame as well as high levels of polymorphism. Elevated Ka/Ks ratios within the Pan-Homo clade suggest a history of positive selection at semenogelin I. Our results suggest that there is a positive relationship between the intensity of sperm competition in a species and the strength of positive Darwinian selection on the seminal protein semenogelin I.

Animals↗

Comparative genomic analysis of human and chimpanzee indicates a key role for indels in primate evolution.

Sequence comparison of humans and chimpanzees is of interest to understand the mechanisms behind primate evolution. Here we present an independent analysis of human chromosome 21 and the high-quality BAC clone sequences of the homologous chimpanzee chromosome 22. In contrast to previous studies, we have used global alignment methods and Ensembl predictions of protein coding genes (n = 224) for the analysis. Divergence due to insertions and deletions (indels) along with substitutions was examined separately for different genomic features (coding, noncoding genic, and intergenic sequence). The major part of the genomic divergence could be attributed to indels (5.07%), while the nucleotide divergence was estimated as 1.52%. Thus the total divergence was estimated as 6.58%. When excluding repeats and low-complexity DNA the total divergence decreased to 2.37%. The chromosomal distribution of nucleotide substitutions and indel events was significantly correlated. To further examine the role of indels in primate evolution we focused on coding sequences. Indels were found within the coding sequence of 13% of the genes and approximately half of the indels have not been reported previously. In 5% of the chimpanzee genes, indels or substitutions caused premature stop codons that rendered the affected transcripts nonfunctional. Taken together, our findings demonstrate that indels comprise the majority of the genomic divergence. Furthermore, indels occur frequently in coding sequences. Our results thereby support the hypothesis that indels may have a key role in primate evolution.

Animals↗