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Evolution of a HOXB6 intergenic region within the great apes and humans.

Data accumulated over the past decade from several loci suggest that nonhuman primates have a greater amount of intraspecific genetic variation relative to humans. In phylogenetic reconstructions among primates that are based on genetic data, therefore, it becomes essential to adequately sample the population(s) being analyzed. Inadequate sampling may not only underestimate variation within any given population, but such an underestimate may confound any phylogenetic or population-specific conclusions implied by the data. Here we present inter- and intraspecific data on the molecular evolution of an approximately 1.0 kb intergenic HOXB6 sequence among humans, common chimpanzees, pygmy chimpanzees, gorillas and orangutans. To date, this study represents the most comprehensive investigation of a noncoding nuclear locus among the great apes and humans that examines the nature and amount of intraspecific variation in DNA sequences. Not only do these HOXB6 data continue to support earlier findings that Homo sapiens sapiens has less genetic variation than any great ape species (Ruano et al., 1992; Deinard & Kidd, 1995), but they strongly suggest that a high level of genetic polymorphism existed within the common ancestor of the African ape clade (Homo-Pan-Gorilla). Despite detecting two nucleotide substitutions linking Pan and Homo, we caution against concluding that the HOXB6 data definitively support a Homo-Pan clade to the exclusion of Gorilla. Rather, we believe that taking into consideration the level of genetic polymorphism that is likely to have existed within the common ancestor, the most prudent conclusion that can be made from all available data, including morphological, karyotypic and genetic data, may be that speciation among Homo-Pan-Gorilla is best represented by a "trichotomy".

Animals↗

Comparative mapping of ZFY in the hominoid apes.

Within our project of comparative mapping of candidate genes for sex-determination/testis differentiation, we used a cloned probe from the human ZFY locus for comparative hybridization studies in hominoids. As in the human, the ZFY probe detects X- and Y-specific restriction fragments in the chimpanzee, the gorilla, the orangutan, and the gibbon. Furthermore, the X-specific hybridization site in the great apes resides in Xp21.3, the same locus defining ZFX in the human. The Y-specific locus of ZFY maps closely to the early replicating pseudoautosomal segment in the telomeric or subtelomeric position of the Y chromosomes of the great apes, again as found in the human. Thus, despite cytogenetically visible structural alterations within the euchromatic parts of the Y chromosomes of the human species and the great apes, a segment of the Y chromosome defined by the pseudoautosomal region and ZFY seems to be more strongly conserved than the rest of the Y chromosome.

Animals↗

The APE nebuliser--a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid.

We report the validation of a new delivery system--aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 microns and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV1 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of 99mTc DTPA, which was collected in a 35 1 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of 99mTc-DTPA. In view of the excellent intrapulmonary deposition of 99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.

Acquired Immunodeficiency Syndrome↗

Unique genomic sequences in human chromosome 16p are conserved in the great apes.

In humans, acute myelomonocytic leukemia (AMML) with abnormal bone marrow eosinophilia is diagnosed by the presence of a pericentric inversion in chromosome 16, involving breakpoints p13;q23 [i.e., inv(16)(p13;q23)]. A pericentric inversion involves breaks that have occurred on the p and q arms and the segment in between is rotated 180 degrees and reattaches. The recent development of a "human micro-coatasome" painting probe for 16p contains unique DNA sequences that fluorescently label only the short arm of chromosome 16, which facilitates the identification of such inversions and represents an ideal tool for analyzing the "divergence/convergence" of the equivalent human chromosome 16 (PTR 18, GGO 17 and PPY 19) in the great apes, chimpanzee, gorilla and orangutan. When the probe is used on the type of pericentric inversion characteristic of AMML, signals are observed on the proximal portions (the regions closest to the centromere) of the long and short arms of chromosome 16. The probe hybridized to only the short arm of all three ape chromosomes and signals were not observed on the long arms, suggesting that a pericentric inversion similar to that seen in AMML has not occurred in any of these great apes.

Animals↗

Comparative study of urinary reproductive hormones in great apes.

Urinary estrone conjugates (E(1)C), pregnanediol-3-glucuronide (PdG), and follicle-stimulating hormone (FSH) were determined by enzyme immunoassays (EIAs) during the normal menstrual cycle in the orangutan, gorilla, chimpanzee, and bonobo. Furthermore, the data were compared to those levels in the human and long-tailed macaque. The results showed a typical preovulatory E(1)C surge and postovulatory increase in PdG in all species. The pattern of E(1)C during the menstrual cycle in the great apes more closely resembled the human than do the long-tailed macaque. A major difference of E(1)C pattern between these species appeared in the luteal phase. In the great apes and the human, E(1)C exhibited two peaks, the first peak detected at approximately mid cycle and the second peak detected during the luteal phase. On the other hand, in the long-tailed macaque, increase of E(1)C in the luteal phase was small or nonexistent. The gorilla, chimpanzee, and bonobo exhibited similar PdG trends. The orangutan excreted one tenth less PdG than these species during the luteal phase. The long-tailed macaque also excreted low levels of PdG. The patterns of FSH in orangutan, chimpanzee, bonobo and long-tailed macaque showed a marked mid-cycle rise and an early follicular phase rise, similar to those in the human. Comparing similar taxa, a large difference was found in FSH of gorilla; there were three peaks during the menstrual cycle. Thus, there is considerable species variation in the excretion of these hormones during the menstrual cycle and comparative studies could be approached with a single method. The methods and baseline data presented here provide the basis for a practical approach to evaluation and monitoring of ovarian events in the female great apes.

Animals↗

Patterns of C-heterochromatin and telomeric DNA in two representative groups of small apes, the genera Hylobates and Symphalangus.

The course of chromosome evolution in small apes is still not clear, though painting analyses have opened the way for elucidating the puzzle. Even the C-banding pattern of the lar-group of gibbons (the genus Hylobates) is not clarified yet, although our previous studies suggested that lar-group gibbons have a unique C-banding pattern. We therefore made observations to establish C-banded karyotypes of the agile gibbons included in the lar-group. The data were compared with those of siamangs (the genus Symphalangus), which carry distinctive C-bands, to determine the chromosomal patterns in each group. C-banded chromosomes of agile gibbons showed several terminal, interstitial and paracentric bands, whose patterns are specific for each chromosome, whereas the C-bands of siamangs were located only at the terminal and centromeric regions in most chromosomes. Moreover, the C-bands of agile gibbons and siamangs were shown to be G+C-rich and A+T-rich DNA, respectively, by DAPI/C-band sequential staining. Additionally, PRINS labelling with a telomere primer revealed that agile gibbons have telomeric DNA only at chromosome ends where there is no C-band (non-telomeric heterochromatin), whereas the telomeric DNA of siamangs is located in the terminal C-banded regions (telomeric heterochromatin). Although the evolutionary mechanisms in small apes are still unknown, C-banding patterns and distribution of telomeric DNA sequences should provide valuable data to deduce the evolutionary pathways of small apes.

AT Rich Sequence↗

Face touching in monkeys, apes and man evolutionary origins and cerebral asymmetry.

The evolution of face touching, i.e. the use of the hand to touch the individual's own face, was studied in monkeys, apes and man with the object of examining which hand is used and which part of the face is touched. Monkeys show little if any face touching. Gorillas, orang- utans and chimpanzees show face-touching comparable to man. Left-hand face touching was superior to right-hand touching for both apes and humans. One feature which distinguished humans from other apes was the frequency of chin touching, which is generally high for man. It has been suggested that emotions are expressed more intensely on the left side of the face and it was thought that the left hand is used by the right hemisphere as a special pointer to heighten the effect of this.

Animals↗

Nucleotide sequence of the large terminal repeat of two different strains of gibbon ape leukemia virus.

Gibbon ape leukemia virus, SEATO strain (GaLV-SEATO), a virus that induces myeloid leukemia in gibbon apes, and GaLV, San Francisco strain (GaLV-SF), a virus associated etiologically with lymphocytic leukemia in gibbon apes, have been molecularly cloned. The complete nucleotide sequence of the large terminal repeats (LTRs) of both viruses are reported and compared to the previously published nucleotide sequence of the LTR of another member of the same virus group, the simian sarcoma virus (SSV). Substantial homology is evident among all three LTR sequences. The most striking feature of the GaLV-SEATO LTR is the presence of a 45-bp tandem direct repeat in the U3 region, an area likely to contain transcriptional enhancers. Both GaLV-SEATO and GaLV-SF contain a deletion in U3 when compared to SSV. Each of the three LTRs differ from the other two by short deletions in R-U5 and short additions in U3, as well as by numerous point mutations. The possibility that the structural changes observed in the LTR contribute to the differences in the pathogenic effects of these viruses is discussed.

Animals↗

Cis-acting transcriptional regulatory sequences in the gibbon ape leukemia virus (GALV) long terminal repeat.

Gibbon ape leukemia viruses (GALV) are a group of retroviruses which have been associated with hematopoietic neoplasms in primates. Two of the viruses, GALV-SEATO and GALV-San Francisco (GALV-SF), are associated with myeloid and lymphocytic leukemias, respectively, in apes. Using an assay based on the transient expression of the bacterial gene chloramphenicol acetyltransferase (CAT), we examined the transcriptional activity of GALV-SEATO and GALV-SF. The results suggest that high level expression of GALV is due primarily to cis-acting enhancer sequences. Sequence delineation analysis of GALV-SEATO showed the GALV-SEATO enhancer sequences to be located within a 45-bp tandem repeat in GALV-SEATO. GALV-SF, which has two- to fivefold lower transcriptional activity, contains only a single copy of the 45-bp element with 6-bp differences from those in the GALV-SEATO enhancer element. This 45-bp element is highly homologous to sequences within the LTRs of several murine leukemia viruses but has not been examined for enhancer function in these retroviruses. Expression of GALV was not restricted to hematopoietic cells but was extraordinarily high in MLA 144 cells, a gibbon ape T-cell line known to be infected with GALV-SF. However, expression of constructs containing the CAT gene directed by GALV-SEATO LTR sequences was similar in uninfected and GALV-infected fibroblasts, indicating the lack of virally encoded or virally induced trans-activating factors capable of increasing expression in these cells.

Acetyltransferases↗

Evolution of the pseudoautosomal boundary in Old World monkeys and great apes.

Mammalian sex chromosomes are divided into sex-specific and pseudoautosomal regions. Sequences in the pseudoautosomal region recombine between the sex chromosomes; the sex-specific sequences normally do not. The interface between sex-specific and pseudoautosomal sequences is the pseudoautosomal boundary. The boundary is the centromeric limit to recombination in the pseudoautosomal region. In man, an Alu repeat element is found inserted at the boundary on the Y chromosome. In the evolutionary comparison conducted here, the Alu repeat element is found at the Y boundary in great apes, but it is not found there in two Old World monkeys. During the evolution of the Old World monkey and great ape lineages, homology between the sex chromosomes was maintained by recombination in the sequences telomeric to the Alu insertion site. The Alu repeat element did not create the present-day boundary; instead, it inserted at the preexisting boundary after the Old World monkey and great ape lineages diverged.

Animals↗

Comparative studies on an antigenicity of plasma proteins from humans and apes by ELISA: a close relationship of chimpanzee and human.

1. Antigenic differences between human and ape plasma proteins were quantitatively investigated by enzyme-linked immunosorbent assay (ELISA) using antisera against human and chimpanzee plasmas. 2. With anti-human plasma serum, both the chimpanzee and gorilla were very close to the human, although the chimpanzee was slightly closer to the human than to the gorilla; relative immunological distance (relative ID) of the chimpanzee was 71, while that of the gorilla was 74. 3. With anti-chimpanzee plasma serum, the chimpanzee was found to be closely related to the human; relative ID of the chimpanzee was 58, while that of the gorilla was 75. 4. From these a molecular phylogeny for humans and apes was deduced; among living apes, the chimpanzee is the most closely related species to the human.

Animals↗

Demographic history and genetic differentiation in apes.

Comparisons of genetic variation between humans and great apes are hampered by the fact that we still know little about the demographics and evolutionary history of the latter species. In addition, characterizing ape genetic variation is important because they are threatened with extinction, and knowledge about genetic differentiation among groups may guide conservation efforts. We sequenced multiple intergenic autosomal regions totaling 22,400 base pairs (bp) in ten individuals each from western, central, and eastern chimpanzee groups and in nine bonobos, and 16,000 bp in ten Bornean and six Sumatran orangutans. These regions are analyzed together with homologous information from three human populations and gorillas. We find that whereas orangutans have the highest diversity, western chimpanzees have the lowest, and that the demographic histories of most groups differ drastically. Special attention should therefore be paid to sampling strategies and the statistics chosen when comparing levels of variation within and among groups. Finally, we find that the extent of genetic differentiation among "subspecies" of chimpanzees and orangutans is comparable to that seen among human populations, calling the validity of the "subspecies" concept in apes into question.

Animals↗

Making sense of behavioral irregularities of great apes.

Psychopathology, mental illness, and psychiatric treatment are concepts relevant to modern medicine and medical psychology and replete with cumbersome intellectual and literary baggage. They bear the imprint of suppositions, world views, and general beliefs and values exemplified in the science, history, and general culture of Anglo European societies. The study in higher apes of phenomena addressed by such concepts raises conceptual dilemmas, usually termed speciesism and anthropomorphism, not unlike those encountered in comparative human studies of similar phenomena across cultures and historical periods, namely, ethnocentrism and anachronism. The authors' synthesis of literature and their analysis of the implications of higher ape psychopathology represent an epistemically compelling account that broadens the scope of the comparative study of behavioral irregularities, a topic that provides a different slant for examining challenging questions in evolutionary biology and primatology, such as cognition, self awareness, intentional behavior, culture and behavioral traditions, social intelligence, sickness and healing, and altruism. Theoretical and empirical study of this topic expands formulation and can help provide informative answers about human evolution as well as essential features of human psychiatric syndromes, with potential practical implications. The study of psychopathology of higher apes and other non human primates represents an appropriate focus for neuroscience and bio-behavioral sciences.

Animals↗

Yerkes, Hamilton and the experimental study of the ape mind: from evolutionary psychiatry to eugenic politics.

Robert Yerkes is a pivotal figure in American psychology and primatology in the first half of the twentieth century. As is well known, Yerkes first studied ape intelligence in 1915, on a visit to the private California laboratory of the psychiatrist Gilbert Hamilton, a former student. Less widely appreciated is how far the work done at the Hamilton lab, in its aims and ambitions as well as its techniques, served as a template for much of Yerkes's research thereafter. This paper uses the Hamilton-Yerkes relationship to re-examine Yerkes's career and, more generally, that of American psychology in the early twentieth century. Three points especially are emphasized: first, the role of Freudian psychoanalysis as a spur to Hamilton's experimental studies of ape intelligence; second, the importance of Hamilton's laboratory, with its semi-wild population of monkeys and ape, as a model for Yerkes's efforts to create a laboratory of his own; and third, the influence on Yerkes of Hamilton's optimism about experimental psychological studies of nonhuman primates as a source of lessons beneficial to a troubled human world.

Adult↗

Comparison of the promoters of the mouse (APEX) and human (APE) apurinic endonuclease genes.

We investigated the minimal promoter of APEX, which encodes mouse apurinic DNA repair endonuclease. A 1.85-kb fragment with APEX upstream sequences and approximately 290 bp of the transcribed region linked to a chloramphenicol acetyltransferase (CAT) reporter gene was assayed by transient transfection in NIH-3T3 cells. The minimal APEX promoter was comprised of approximately 190 bp of upstream and approximately 170 bp of transcribed DNA (exon 1 and most of intron 1). This approximately 360-bp region contains two CCAAT boxes and other consensus protein binding sites, but no TATA box. Deletion of the 5'-most CCAAT box decreased activity approximately 5-fold. The second CCAAT box (situated in exon 1) may play an independent role in APEX expression. Transcription start sites have been identified downstream of the second CCAAT box, and DNase I footprinting demonstrated NIH-3T3 nuclear proteins binding this region, including an Spl site located between the CCAAT boxes. Electrophoretic mobility-shift assays indicated binding by purified Sp1. Mouse proteins did not bind three myc-like (USF) sites in the APEX promoter, in contrast to the APE promoter. The APEX and APE promoter had similar activity in Hela cells, but in mouse cells, the murine promoter had approximately 5-fold higher activity than did the human promoter. Both the APEX and APE promoters exhibited bidirectional activity in their cognate cells.

3T3 Cells↗

Differential resource utilization by extant great apes and australopithecines: towards solving the C4 conundrum.

Morphological and biogeochemical evidence suggest that australopithecines had diets markedly different from those of extant great apes. Stable carbon isotope analysis, for example, has shown that significant amounts of the carbon consumed by australopithecines were derived from C(4) photosynthesis in plants. This means that australopithecines were eating large quantities of C(4) plants such as tropical grasses and sedges, or were eating animals that were themselves eating C(4) plants. In contrast, there is no evidence that modern apes consume appreciable amounts of any of these foods, even in the most arid extents of their ranges where these foods are most prevalent. Environmental reconstructions of early australopithecine environments overlap with modern chimpanzee habitats. This, in conjunction with the stable isotope evidence, suggests that australopithecines and great apes, even in similar environments, would utilize available resources differently. Thus, the desire or capacity to use C(4) foods may be a basal character of our lineage. We do not know, however, which of the nutritionally disparate C(4) foods were utilized by hominids. Here we discuss which C(4) resources were most likely consumed by australopithecines, as well as the potential nutritional, physiological, and social consequences of eating these foods.

Animals↗

Comparative and familial analysis of handedness in great apes.

Historically, population-level handedness has been considered a hallmark of human evolution. Whether nonhuman primates exhibit population-level handedness remains a topic of considerable debate. This paper summarizes published data on handedness in great apes. Comparative analysis indicated that chimpanzees and bonobos show population-level right handedness, whereas gorillas and orangutans do not. All ape species showed evidence of population-level handedness when considering specific tasks. Familial analyses in chimpanzees indicated that offspring and maternal (but not paternal) handedness was significantly positively correlated, but this finding was contingent upon the classification criteria used to evaluate hand preference. Overall, the proportion of right handedness is lower in great apes compared with humans, and various methodological and theoretical explanations for this discrepancy are discussed.

Animals↗

Constraints on great apes' imitation: model and action selectivity in rehabilitant orangutan (Pongo pygmaeus) imitation.

We discuss selectivity in great ape imitation, on the basis of an observational study of spontaneous imitation in free-ranging rehabilitant orangutans (Pongo pygmaeus). Research on great ape imitation has neglected selectivity, although comparative evidence suggests it may be important. We observed orangutans in central Indonesian Borneo and assessed patterns in the models and actions they spontaneously imitated. The patterns we found resembled those reported in humans. Orangutans preferred models with whom they had positive affective relationships (e.g., important caregiver or older sibling) and actions that reflected their current competence, were receptively familiar, and were relevant to tasks that faced them. Both developmental and individual variability were found. We discuss the probable functions of imitation for great apes and the role of selectivity in directing it. We also make suggestions for more effective elicitation of imitation.

Affect↗