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Comparative mapping of DNA probes derived from the V kappa immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) of cosmid clones of human V kappa gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the kappa locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen-q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V kappa I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V kappa region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution.

Animals↗

Mental rehearsal in great apes (Pan troglodytes and Pongo pygmaeus) and children.

The ability to rehearse possible future courses of action in the mind is an important feature of advanced social cognition in humans, and the "social brain" hypothesis implies that it might also be a feature of primate social cognition. We tested two chimpanzees, six orangutans and 63 children aged 3-7 years on a set of four puzzle boxes, half of which were presented with an opportunity to observe the box before being allowed to open it ("prior view"), the others being given without an opportunity to examine the boxes before handling them ("no prior view"). When learning effects are partialled out, puzzle boxes in the "prior view" condition were opened significantly faster than boxes given in the "no prior view" condition by the children, but not by either of the great apes. The three species differ significantly in the speed with which they opened boxes in the "no prior view" condition. The three species' performance on this task was a function of relative frontal lobe volume, suggesting that it may be possible to identify quantitative neuropsychological differences between species.

Algorithms↗

Primatology: advanced ape technology.

New findings from African rainforests show chimpanzees to have impressively advanced technology. They make tools of vegetation to harvest termites as in East and West Africa, but some apes in Central Africa show different techniques and tool sets geared for different tasks.

Africa↗

NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells.

DNA glycosylases/AP lyases initiate repair of oxidized bases in the genomes of all organisms by excising these lesions and then cleaving the DNA strand at the resulting abasic (AP) sites and generate 3' phospho alpha,beta-unsaturated aldehyde (3' PUA) or 3' phosphate (3' P) terminus. In Escherichia coli, the AP-endonucleases (APEs) hydrolyze both 3' blocking groups (3' PUA and 3' P) to generate the 3'-OH termini needed for repair synthesis. In mammalian cells, the previously characterized DNA glycosylases, NTH1 and OGG1, produce 3' PUA, which is removed by the only AP-endonuclease, APE1. However, APE1 is barely active in removing 3' phosphate generated by the recently discovered mammalian DNA glycosylases NEIL1 and NEIL2. We showed earlier that the 3' phosphate generated by NEIL1 is efficiently removed by polynucleotide kinase (PNK) and not APE1. Here we show that the NEIL2-initiated repair of 5-hydroxyuracil (5-OHU) similarly requires PNK. We have also observed stable interaction between NEIL2 and other BER proteins DNA polymerase beta (Pol beta), DNA ligase IIIalpha (Lig IIIalpha) and XRCC1. In spite of their limited sequence homology, NEIL1 and NEIL2 interact with the same domains of Pol beta and Lig IIIalpha. Surprisingly, while the catalytically dispensable C-terminal region of NEIL1 is the common interacting domain, the essential N-terminal segment of NEIL2 is involved in analogous interaction. The BER proteins including NEIL2, PNK, Pol beta, Lig IIIalpha and XRCC1 (but not APE1) could be isolated as a complex from human cells, competent for repair of 5-OHU in plasmid DNA.

Animals↗

Focusing on comparative ape population genetics in the post-genomic age.

The initial human and chimpanzee genome sequences have been published, and additional primate genomes, including those of gorilla and orang-utan, are in progress. With these new resources, we can now address what makes our species unique, by focusing on the underlying genetic differences associated with phenotypes. Comparative primate population genomics, including studies of structural changes, mobile elements, gene expression and functional analyses, will shed light on how natural selection and population demography are involved in the processes that lead to differences among great apes. Historically, this research has focused on the human perspective; however, we will learn much about ourselves with a focus on genomic diversity in hominoids as a group.

Animals↗

Does space in the jaw influence the timing of molar crown initiation? A model using baboons (Papio anubis) and great apes (Pan troglodytes, Pan paniscus).

Radiographic and histological studies of baboon (Papio hamadryas, P. anubis) and chimpanzee (Pan troglodytes) permanent tooth development have found that periods of molar crown mineralization overlap markedly in chimpanzees but are staggered in baboons. Here we test the hypothesis that these intertaxon differences in molar initiation are primarily due to the space available in the mandibles of each species for these teeth. This study includes radiographic, linear measurement, and three-dimensional (3D) coordinate landmark data taken from baboon (Papio anubis n=51) and great ape (Pan paniscus n=43, P. troglodytes n=60) mandibles and permanent molars across a broad developmental range for each taxon. Unexpectedly, 3D multivariate statistical shape analysis of the molar crypt, crown, and root data shows that all three species trajectories of molar row shape change are indistinguishable from each other. Qualitative analysis of these 3D data reveals subtle and inconclusive intergeneric differences in the space maintained between adjacent molars during growth. The space distal to each newly initiated molar is slightly greater in the baboon. Bivariate analyses comparing molar row and mandibular corpus proportions in Papio and Pan fail to show clear or consistent taxonomic differences in the ratio of space afforded developing molars in the alveolar bone. Thus, there is a poor correlation between mandibular proportion and both intermolar spacing and 3D molar development pattern. Contrary to earlier studies, these results suggest that pattern of molar crown initiation and temporal overlap of adjacent mineralizing crowns is not significantly different between Papio and Pan. This may be due in part to the inclusion here of not only 3D molar crown data but also 3D molar crypt data. This study strongly refutes the hypothesis that space available in the mandible directly underlies different times of permanent molar crown initiation between Papio and Pan.

Animals↗

Distinguishing humans from great apes with AluYb8 repeats.

Humans and chimpanzees share some 99% of DNA and amino acid identity, yet they exhibit important biomedical, morphological, and cognitive differences, difficult to accommodate within the remaining 1% of sequence diversity. Other types of genetic variation must be responsible for the taxonomic differences. Here we trace the evolution of AluYb8 repeats from a single origin at the roots of higher primates to a large increase in their number in humans. We identify nine AluYb8 DNA repeats in the chimpanzee genome compared to over 2200 repeats in the human, which represents a 250-fold increase in the rate of change in the human lineage and far outweighs the 99% sequence similarity between the two species. It is estimated that the average age of the human Yb8Alus is about 3.3 million years (My); almost 10% of them are identical in sequence, and hence are of recent origin. Genomic variations of this magnitude, distinguishing humans from great apes have not been realized. This explosive Alu expansion must have had a profound effect on the organization of our genome and the architecture of our chromosomes, inferentially altering profiles of gene expression and chromosome choreography in cell division. Additionally, we conclude that this major evolutionary process of Alu proliferation is driven by internal forces, written in the chemistry of DNA, rather than by external selection.

Alu Elements↗

Molecular dating: ape bones agree with chicken entrails.

Molecular time estimates, especially those that employed the 310 million years ago (Mya) date of mammal-bird divergence as the calibration point, were criticized in recent publications. In this article, we estimate the divergence time of primates and rodents, primates and artiodactyls and the different great ape species by using two independent calibration-time ranges and maximally conservative error estimates. We observed a variation of approximately +/-15-20% for most of the molecular time estimates in the 10-100 Mya range. The estimated range of the primate-rodent divergence time, 84-121 Mya, includes the date obtained with the 310 million years calibration point (110 Mya). We conclude that molecular time estimates remain useful tools of evolutionary biology, although utmost caution is required when interpreting the results.

Animals↗

Up-regulation of the redox mediators thioredoxin and apurinic/apyrimidinic excision (APE)/Ref-1 in hypoxic microregions of invasive cervical carcinomas, mapped using multispectral, wide-field fluorescence image analysis.

Thioredoxin and apurinic/apyrimidinic excision (APE)/ref-1 are important redox mediators in biochemical pathways that promote cell survival under adverse conditions including hypoxia and oxidative stress. For example, elevated levels occur surrounding vascular infarcts and protect from reperfusion injury. Because elevated thioredoxin or APE/ref-1 is also associated with resistance to certain forms of cancer treatment, we examined their tissue distribution in a series of 110 cervical carcinoma biopsies. Analysis was done using a quadruple fluorescence imaging technique, incorporating carbonic anhydrase IX (CAIX) immunofluorescence to outline hypoxic microregions and 4',6-diamidino-2-phenylindole to localize nuclear staining of thioredoxin and APE/ref-1. A scanning autostage was used to image the entire tissue section. Thioredoxin and APE/ref-1 levels were expressed as the average pixel brightness in tumor tissue, subdivided based on CAIX and 4',6-diamidino-2-phenylindole staining. Results showed that the nuclear and cytoplasmic levels of thioredoxin were similar, whereas APE/ref-1 expression was greater in nuclei. Neither of these markers was predictive of outcome in this series of patients treated with radical radiotherapy. Both proteins showed highly significant elevations in CAIX-positive regions compared to CAIX-negative regions, and there was a nonsignificant trend for this effect to be greater in adenocarcinomas compared to squamous cell carcinomas. Levels of APE/ref-1 decreased with increasing tumor grade, but the expression was similar in CAIX-positive regions of poorly differentiated tumors compared to moderately or well-differentiated tumors. Elevated expression of thioredoxin and APE/ref-1 might promote cancer cell survival in hypoxic microenvironments of cervical carcinomas.

Adult↗

Removal by human apurinic/apyrimidinic endonuclease 1 (Ape 1) and Escherichia coli exonuclease III of 3'-phosphoglycolates from DNA treated with neocarzinostatin, calicheamicin, and gamma-radiation.

DNA strand breaks with terminal 3'-phosphoglycolate groups are produced by agents that can abstract the hydrogen atom from the 4'-carbon of DNA deoxyribose groups. Included among these agents are gamma-radiation (via the OH radical) and enediyne compounds, such as neocarzinostatin and calicheamicin. However, while the majority of radiation-induced phosphoglycolates are found at single-strand breaks, most of the phosphoglycolates generated by these two enediynes are found at bistranded lesions, including double-strand breaks. Using a 32P-post-labelling assay, we have compared the enzyme-catalyzed removal of phosphoglycolates induced by each of these agents. Both human apurinic/apyrimidinic endonuclease 1 (Ape 1) and its Escherichia coli homolog exonuclease III rapidly removed over 80% of phosphoglycolates from gamma-irradiated DNA, although there appeared to be a small resistant subpopulation. The neocarzinostatin-induced phosphoglycolates were removed more slowly, though not to completion, while the calicheamicin-induced phosphoglycolates were extremely refractory to both enzymes. These data suggest that unless other enzymes are capable of acting upon the phosphoglycolate termini at enediyne-induced double-strand breaks, such termini will be resistant to end rejoining repair pathways.

Aminoglycosides↗

Genome of the apes.

The Human Genome Project has generated both the information and technological infrastructure needed to accelerate genetic comparisons between humans and the African great apes (chimpanzees and gorillas). Sequence and chromosomal organization differences between these highly related genomes will provide clues to the genetic basis for recently evolved, specifically human traits such as bipedal gait and advanced cognitive function. Recent studies comparing the primate genomes have the potential to affect many aspects of human biomedical research and could benefit primate conservation efforts.

Animals↗

A comparison of taste thresholds for sweet and astringent-tasting compounds in great apes.

Taste responses to fructose and tannic acid were compared between great apes using the 'two-bottle test' with tests of brief duration. The taste thresholds for fructose were [10-20] mM in Pongo pygmaeus, [40-50] mM in Pan troglodytes, and [70-80] mM in Gorilla gorilla. Inhibition thresholds for tannic acid were [2.9-3.5] mM in Pongo and [2.9-5.9] mM in Pan. Gorillas apparently significantly preferred tannins at low concentrations ([0.59-5.9] mM) but rejected concentrations above [8.8-14.7] mM. These results are discussed in relation to the effects of phylogenetic inertia and biological adaptation.

Animals↗

Beyond species: Il'ya Ivanov and his experiments on cross-breeding humans and anthropoid apes.

The possibility of crossing humans with other anthropoid species has been discussed in fiction as well as in scientific literature during the twentieth century. Professor Il'ya Ivanov's attempt to achieve this was critical for the beginning of organized primate research in the Soviet Union, and remains one of the most interesting and controversial experiments that was ever done on non-human primates. The possibility of removing the boundary that separates humans from other animal species, apes in particular, is loaded with important political meaning and violates cultural and ethical taboos. The history of Ivanov's scientific experiment thus helps to reveal some of the twentieth-century's important cultural conventions and hidden assumptions about human nature, species, and social hierarchy.

Animal Experimentation↗

Interspecies comparative genome hybridization and interspecies representational difference analysis reveal gross DNA differences between humans and great apes.

Comparative chromosome G-/R-banding, comparative gene mapping and chromosome painting techniques have demonstrated that only few chromosomal rearrangements occurred during great ape and human evolution. Interspecies comparative genome hybridization (CGH), used here in this study, between human, gorilla and pygmy chimpanzee revealed species-specific regions in all three species. In contrast to the human, a far more complex distribution of species-specific blocks was detected with CGH in gorilla and pygmy chimpanzee. Most of these blocks coincide with already described heterochromatic regions on gorilla and chimpanzee chromosomes. Representational difference analysis (RDA) was used to subtract the complex genome of gorilla against human in order to enrich gorilla-specific DNA sequences. Gorilla-specific clones isolated with this technique revealed a 32-bp repeat unit. These clones were mapped by fluorescence in situ hybridization (FISH) to the telomeric regions of gorilla chromosomes that had been shown by interspecies CGH to contain species-specific sequences.

Animals↗

Species-specific evolution of repeated DNA sequences in great apes.

DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee share more than 98% homology. Comparative chromosome painting and gene mapping have demonstrated that only a few rearrangements of a putative ancestral mammalian genome occurred during great ape and human evolution. However, interspecies representational difference analysis (RDA) of the gorilla between human and gorilla revealed gorilla-specific DNA sequences. Cloning and sequencing of gorilla-specific DNA sequences indicate that there are repetitive elements. Gorilla-specific DNA sequences were mapped by fluorescence in-situ hybridization (FISH) to the subcentromeric/centromeric regions of three pairs of gorilla submetacentric chromosomes. These sequences could represent either ancient sequences that got lost in other species, such as human and orang-utan, or, more likely, recent sequences which evolved or originated specifically in the gorilla genome.

Animals↗

Comparative mapping of human alphoid satellite DNA repeat sequences in the great apes.

Heterochromatic regions of chromosomes contain highly repetitive, tandemly arranged DNA sequences that undergo very rapid variation compared to unique DNA sequences that are predominantly conserved. In this study the chromosomal basis of speciation has been looked at in terms of repeat sequences. We have hybridized twenty-one chromosome-specific human alphoid satellite DNA probes to metaphase spreads of the chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), and orangutan (Pongo pygmaeus) to investigate the evolutionary relationship of heterochromatic regions among such hominoid species. The majority of the probes did not hybridize to their corresponding equivalent chromosome but presented hybridization signals on non-corresponding chromosomes. Such observations suggest that rapid changes may have occurred in the ancestral alphoid satellite DNA sequence, resulting in divergence among the great ape species.

Animals↗

Cardiac startle and orienting responses in the great apes.

Cardiac patterns of startle and orienting in response to auditory and vibrotactile stimuli were investigated in the infant chimpanzee and gorilla. Results revealed a notable cardiac acceleration in response to the initial presentations of stimuli of either modality. This acceleratory response appeared to reflect the cardiac correlate of startle and was closely associated with the elicitation of somatic startle responses. This initial cardiac acceleration was subject to rapid habituation and was replaced on subsequent trials by cardiac deceleration, which appeared to reflect the orienting response. Results from the chimpanzees and the gorilla were similar, although a slower rate of habituation was apparent in the gorilla. Taken together, these results are highly consistent with those obtained from humans and monkeys, and they provide the first characterization of cardiac patterns associated with startle and orienting responses in the great apes.

Animals↗

How the great apes (Pan troglodytes, Pongo pygmaeus, Pan paniscus, and Gorilla gorilla) perform on the reversed contingency task: the effects of food quantity and food visibility.

S. T. Boysen and G. G. Berntson (1995) found that chimpanzees performed poorly on a reversed contingency task in which they had to point to the smaller of 2 food quantities to acquire the larger quantity. The authors compared the performance of 4 great ape species (Pan troglodytes, Pongo pygmaeus, Pan paniscus, and Gorilla gorilla) on the reversed contingency task while manipulating food quantity (0-4 or 1-4) and food visibility (visible pairs or covered pairs). Results showed no systematic species differences but large individual differences. Some individuals of each species were able to solve the reversed contingency task. Both quantity and visibility of the food items had a significant effect on performance. Subjects performed better when the disparity between quantities was smaller and the quantities were not directly visible.

Age Factors↗