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PubMed1988

Segregation of functionally distinct axons in the monkey's optic tract.

The classical neuro-ophthalmologic literature describes the organization of the primate's optic tract as containing a single topographic representation of the complete contralateral visual hemifield. In contrast, cats have separate visual field representations for the optic axons of the functionally distinct retinal ganglion cell classes. As the line of decussation for each ganglion cell class in the cat occupies a different location on the retinal surface, whereas in primates they are all superimposed, such a species difference might be expected. We report that implants of horseradish peroxidase placed in either the deep or superficial extremes of the monkey's optic tract produce retrograde labelling of distinct retinal ganglion cell classes, and produce anterograde labelling confined to distinct laminae of the lateral geniculate nucleus. Hence, the optic tract of the primate cannot contain a single representation of the contralateral visual hemifield; rather, independent visual field representations for the functionally distinct optic axons must exist. Their anatomical segregation may account for the clinical observation of selective impairments of distinct visual abilities following partial interruption of the optic tract in man.

Animals↗
PubMed1989

Mutation rates differ among regions of the mammalian genome.

In the traditional view of molecular evolution, the rate of point mutation is uniform over the genome of an organism and variation in the rate of nucleotide substitution among DNA regions reflects differential selective constraints. Here we provide evidence for significant variation in mutation rate among regions in the mammalian genome. We show first that substitutions at silent (degenerate) sites in protein-coding genes in mammals seem to be effectively neutral (or nearly so) as they do not occur significantly less frequently than substitutions in pseudogenes. We then show that the rate of silent substitution varies among genes and is correlated with the base composition of genes and their flanking DNA. This implies that the variation in both silent substitution rate and base composition can be attributed to systematic differences in the rate and pattern of mutation over regions of the genome. We propose that the differences arise because mutation patterns vary with the timing of replication of different chromosomal regions in the germline. This hypothesis can account for both the origin of isochores in mammalian genomes and the observation that silent nucleotide substitutions in different mammalian genes do not have the same molecular clock.

Animals↗
PubMed1989

An African primate lentivirus (SIVsm) closely related to HIV-2.

The ancestors of the human immunodeficiency viruses (HIV-1 and HIV-2) may have evolved from a reservoir of African nonhuman primate lentiviruses, termed simian immunodeficiency viruses (SIV). None of the SIV strains characterized so far are closely related to HIV-1. HIV-2, however, is closely related to SIV (SIVmac) isolated from captive rhesus macaques (Macaca mulatta). SIV infection of feral Asian macaques has not been demonstrated by serological surveys. Thus, macaques may have acquired SIV in captivity by cross-species transmission from an SIV-infected African primate. Sooty mangabeys (Cercocebus atys), an African primate species indigenous to West Africa, however, are infected with SIV (SIVsm) both in captivity and in the wild (P. Fultz, personal communication). We have molecularly cloned and sequenced SIVsm and report here that it is closely related to SIVmac and HIV-2. These results suggest that SIVsm has infected macaques in captivity and humans in West Africa and evolved as SIVmac and HIV-2, respectively.

Africa↗
PubMed1990

Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-PBj14.

The PBj14 isolate of simian immunodeficiency virus from sooty mangabey monkeys (SIVSMM-PBj14) is the most acutely pathogenic primate lentivirus so far described, always causing fatal disease in pig-tailed macaques (Macaca nemestrina) within 8 days of inoculation. As a first step in identifying viral genes and gene products that influence pathogenicity, the SIVSMM-PBj14 genome was amplified by the polymerase chain reaction as 5' and 3' genomic halves of 5.1 and 5.8 kilobases, respectively, and molecularly cloned. DNA sequence analysis revealed a high degree of conservation with other SIVs, except for a 22-base-pair duplication in the enhancer region of the viral long terminal repeat which included a second binding site for the transcription factor NF-kappa B. Of six genomic halves examined, four contributed to the formation of infectious virus that induced acute disease and death in pig-tailed macaques as early as 6 days post-inoculation, with pathology, disease syndromes and kinetics indistinguishable from those induced by the uncloned isolate. To our knowledge this is the first example of acute immunodeficiency disease induced by a molecularly defined lentivirus. Furthermore, the molecularly cloned SIVSMM-PBj14 viruses share with the uncloned virus cytopathicity for mangabey CD4+ cells, a property that may correlate with their observed pathogenicity in vivo.

Animals↗
PubMed2000

Rapid evolution of male reproductive genes in the descent of man.

A diverse body of morphological and genetic evidence has suggested that traits pertaining to male reproduction may have evolved much more rapidly than other types of character. Recently, DNA sequence comparisons have also shown a very high level of divergence in male reproductive proteins between closely related Drosophila species, among marine invertebrates and between mouse and rat. Here we show that rapid evolution of male reproductive genes is observable in primates and is quite notable in the lineages to human and chimpanzee. Nevertheless, rapid evolution by itself is not necessarily an indication of positive darwinian selection; relaxation of negative selection is often equally compatible with the DNA sequence data. By taking three statistical approaches, we show that positive darwinian selection is often the driving force behind this rapid evolution. These results open up opportunities to test the hypothesis that sexual selection plays some role in the molecular evolution of higher primates.

Amino Acid Substitution↗
PubMed1995

Insertions and duplications of mtDNA in the nuclear genomes of Old World monkeys and hominoids.

Using oligonucleotide primers designed to match conserved regions of mammalian mitochondrial DNA (mtDNA), we have amplified and sequenced two divergent cytochrome b nuclear pseudogenes from orangutan cellular DNA. Evolutionary analysis suggests that a nuclear transfer occurred about 30 million years ago on the lineage leading to the catarrhines (Old World monkeys and hominoids), and involved a long (at least 3 kilobases), probably damaged, piece of mtDNA. After this transfer, the pseudogene duplicated, giving rise to the two copies that are probably present in all hominoids, including humans. More recent transfers involving the entire cytochrome b gene have also occurred in the Old World monkeys. Such nuclear copies of mtDNA can confound phylogenetic and population genetic studies, and be an insidious source of DNA contamination of 'ancient' and forensic DNA. Indeed, contamination with these anciently transferred human pseudogenes is almost certainly the source of the cytochrome b sequences recently reported from 'dinosaur bone DNA'.

Animals↗
PubMed1997

Earliest known Old World monkey skull.

Similarities of the skull are commonly used to support hypotheses of ancestor-descendant relationships between fossil and living ape genera, especially between the late Miocene apes Sivapithecus and Dryopithecus from Eurasia and the living orang-utan (Pongo) from Borneo and Sumatra. Yet determining whether craniofacial traits shared by extant and Miocene apes are primitive or derived is severely hampered by the rarity of well-preserved fossil crania, particularly of early members of their closest outgroup, the Old World monkeys (Cercopithecoidea). The discovery of a complete and undistorted skull of Victoriapithecus at middle Miocene deposits from Maboko Island, Kenya, provides evidence of intact cranial-vault and basicranial morphology, brain size and craniofacial hafting for a primate from between 32 and 7 million years ago. Victoriapithecus represents a branch of Old World monkey that is intermediate between extant cercopithecids (Colobinae and Cercopithecinae) and the common ancestor they shared with apes (Hominoidea). The skull preserves traits widely thought to be derived for extant and fossil members of a proposed Sivapithecus/Pongo clade, but which now appear to be primitive features of ancestral Old World higher primates in general.

Animals↗
PubMed2006

Inhibition of HIV-1 replication by simian restriction factors, TRIM5alpha and APOBEC3G.

Old World monkey TRIM5alpha targets incoming human immunodeficiency virus type 1 (HIV-1) viral capsid, whereas the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC)3 family hypermutate/degrade viral sequences. Here, we show the potentials of simian TRIM5alpha and APOBEC3G as therapeutic sequences for AIDS gene therapy. Both rhesus and African green monkey (agm) TRIM5alpha efficiently restrict HIV-1 vectors with divergent Gag from different HIV-1 subtypes. Human T cells genetically engineered to express agm-TRIM5alpha block or delay HIV-1 replication. Although agm-APOBEC3G expression alone only transiently suppresses HIV-1 replication, co-expression of agm-APOBEC3G and agm-TRIM5alpha successfully block the virus replication for more than 5 weeks.

Animals↗
PubMed2003

A study of host defence peptide beta-defensin 3 in primates.

We have investigated the molecular evolution of the gene coding for beta-defensin 3 (DEFB103) in 17 primate species including humans. Unlike the DEFB4 genes (coding for beta-defensin 2) [Boniotto, Tossi, Del Pero, Sgubin, Antcheva, Santon and Masters (2003) Genes Immun. 4, 251-257], DEFB103 shows a marked degree of conservation in humans, Great Apes and New and Old World monkeys. Only the Hylobates concolor defensin hcBD3 showed an amino acid variation Arg17-->Trp17 that could have a functional implication, as it disrupts an intramolecular salt bridge with Glu27, which locally decreases the charge and may favour dimerization in the human congener hBD3. This is thought to involve the formation of an intermolecular salt bridge between Glu28 and Lys32 on another monomer [Schibli, Hunter, Aseyev, Starner, Wiencek, McCray, Tack and Vogel (2002) J. Biol. Chem. 277, 8279-8289]. To test the role of dimerization in mediating biological activity, we synthesized hBD3, hcBD3 and an artificial peptide in which the Lys26-Glu27-Glu28 stretch was replaced by the equivalent Phe-Thr-Lys stretch from human beta-defensin 1 and we characterized their structure and anti-microbial activity. Although the structuring and dimerization of these peptides were found to differ significantly, this did not appear to affect markedly the anti-microbial potency, the broad spectrum of activity or the insensitivity of the anti-microbial action to the salinity of the medium.

Amino Acid Sequence↗
PubMed1990

Glycosylation of the envelope glycoprotein gp130 of simian immunodeficiency virus from sooty mangabey (Cercocebus atys).

The envelope glycoprotein 130 ('130' referring to an Mr of 130,000) of simian immunodeficiency virus from sooty mangabey (Cercocebus atys) (SIVSM) was isolated from the cell-free supernatant of the SIVSM-infected human T-cell line H9, metabolically labelled with D-[6-3H]glucosamine. After digestion with Staphylococcus aureus V8 proteinase, radiolabelled N-glycans were liberated from resulting glycopeptides by sequential treatment with endo-beta-N-acetylglucosaminidase H and peptide:N-glycosidase F and fractionated by h.p.l.c. and gel filtration. Individual oligosaccharide species were characterized by enzymic microsequencing, chromatographic analyses and, in part, by acetolysis. The oligosaccharide structures thus established include oligomannosidic glycans with five to nine mannose residues as well as fucosylated and partially sialylated bi-, tri- and tetra-antennary N-acetyl-lactosaminic oligosaccharide species, the latter of which carry, in part, additional galactose residues or N-acetyl-lactosamine repeats. In comparison with the corresponding envelope glycoprotein 120 from human immunodeficiency virus type 1 (HIV-1), propagated in the same cell line [Geyer, Holschbach, Hunsmann and Schneider (1988) J. Biol. Chem. 263, 11760-11767], carbohydrates of the simian glycoprotein were found to consist of decreased amounts of oligomannosidic glycans and increased quantities of higher-branched N-acetyl-lactosaminic species.

Animals↗
PubMed2001

The dorsomedial visual areas in New World and Old World monkeys: homology and function.

The extrastriate cortex near the dorsal midline has been described as part of an 'express' pathway that provides visual input to the premotor cortex. This pathway is considered important for the integration of sensory information about the visual field periphery and the skeletomotor system, especially in relation to the control of arm movements. However, a better understanding of the functional contributions of different parts of this complex has been hampered by the lack of data on the extent and boundaries of its constituent visual areas. Recent studies in macaques have provided the first detailed view of the topographical organization of this region in Old World monkeys. Despite differences in nomenclature, a comparison of the visuotopic organization, myeloarchitecture and connections of the relevant visual areas with those previously studied in New World monkeys reveals a remarkable degree of similarity and helps to clarify the subdivision of function between different areas of the dorsomedial complex. A caudal visual area, named DM or V6, appears to be important for the detection of coherent patterns of movement across wide regions of the visual field, such as those induced during self-motion. A rostral area, named M or V6A, is more directly involved with visuomotor integration. This area receives projections both from DM/V6 and from a separate motion analysis channel, centred on the middle temporal visual area (or V5), which detects the movement of objects in extrapersonal space. These results support the suggestion, made earlier on the basis of more fragmentary evidence, that the areas rostral to the second visual area in dorsal cortex are homologous in all simian primates. Moreover, they emphasize the importance of determining the anatomical organization of the cortex as a prerequisite for elucidating the function of different cortical areas.

Animals↗
PubMedDate not supplied

MIC genes in non-human primates.

MIC molecules belong to the immunoglobulin superfamily, are encoded within the MHC region and are recognized by gamma/delta T-cell receptors. In humans, at least two functional genes (MIC-A* and MIC-B*) and two pseudogenes (MIC-C* and MIC-D*) exist. Functional MIC gene copies are characterized by a high degree of polymorphism, while pseudogenes bear several debilitating mutations either in the putative extracellular region or in the transmembrane region of the molecule. In this study we sequenced these segments of MIC genes in seven non-human primates in order to determine whether debilitating mutations were present. All the MIC primate genes studied were highly homologous to their human counterparts, and cystein residues involved in the maintenance of the immunoglobulin-like structure were highly conserved. Furthermore, none of the MIC genes studied contained stop codons in the extracellular or transmembrane segments of the molecule, which suggests that at least one functional gene copy exists in non-human primates. A distinct family of MHC immunoglobulin-like genes was recently identified within the MHC class I region in humans (Bahram et al., 1994; Leelayuwat et al., 1994). Members of this MIC (MHC class I chain related) gene family belong to the immunoglobulin superfamily. Similar to classical class I MHC genes, they are characterized by three distinct extracellular domains (alpha 1-3), a transmembrane (TM) segment and a cytoplasmic segment, each encoded by a separate exon (Bahram et al., 1994; Bahram et al., 1996). Other similarities between MIC genes and classical MHC genes include a high degree of polymorphism (Fodil et al., 1996; Pellet et al., 1997) and recognition by T-cell receptors (Groh et al., 1998). These findings suggest that the putative MIC-A* chain has evolved for a function that is related to, but quite distinct from, that of typical MHC class I chains.

Amino Acid Sequence↗
PubMed2002

Chronic moderate heat dermatitis (erythema ab igne) in five dogs, three cats and one silvered langur.

Erythema ab igne, an old and rare disease in the human literature, is an erythematous, often pigmented, reticular, macular dermatosis that occurs at the site of repeated exposure to moderate heat. We identified lesions consistent with erythema ab igne in five dogs, three cats and one silvered langur (Trachypithecus cristatus[Raffles, 1821]). In dogs and cats, the cutaneous lesion distribution typically reflected chronic exposure to moderate heat during lateral or sternal recumbency. The silvered langur developed cutaneous lesions on the dorsal neck from exposure to a heat lamp. Principal clinical lesions consisted of irregular areas of alopecia (7/9) and erythema (7/9), sometimes with hyperpigmentation (3/9). Principal histological features consisted of karyomegaly (9/9) and keratinocyte atypia (4/9), scattered apoptotic or vacuolated basal cells and/or apoptotic keratinocytes (6/9), mild mixed mononuclear interstitial or interface dermatitis (9/9) with adnexal atrophy (8/9), and a variable number of wavy eosinophilic elastic fibres (9/9). The presence of these cutaneous lesions in an animal indicates that the environment should be evaluated for exposure to chronic moderate heat, and the heat source should be eliminated or modified to prevent further exposure and progression of lesions.

Animal Husbandry↗
PubMed1999

New world, but not Old World, monkeys carry several genes encoding beta-microseminoprotein.

It was shown by Southern hybridization that cotton-top tamarin and common marmoset, New World monkeys, carry three or more genes encoding beta-microseminoprotein, also known as PSP94. In contrast, the genomes of Old World monkeys, as represented by rhesus macaque and sacred baboon, contain a single gene. Clones containing three different genes encoding beta-microseminoprotein were isolated from a cotton-top tamarin genomic library. They carry two complete genes of four exons and a third gene lacking the first exon. The structure suggests that the three genes are functionally active and give rise to transcripts that are approximately 86% similar in sequence. By sequencing one gene in full, it was shown that the introns carry an excess of interspersed repeats, on average 29% of the introns consist of Alu repeats. A phylogenetic analysis demonstrated that the genes probably arose in New World monkeys after the separation from Old World primates.

Alu Elements↗