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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↗
PubMed2002

Hepatitis viruses: a pandora's box?

The term hepatitis virus is reserved for those viruses that are predominantly hepatotropic, although several new agents have been assigned to this category in the absence of hepatotropism and clinical disease. The hepatitis viruses can be broadly divided into those transmitted via the fecal-oral route, and those by blood, blood products and body fluids. Hepatitis A (picornaviridae), hepatitis B (hepadnaviridae) and hepatitis C (flaviviridae) represent the major public health problems. The epidemiology of hepatitis A virus (HAV) and hepatitis B virus (HBV) is changing in response to vaccination. In the case of HAV, older age groups are now deemed at risk, particularly of fulminant hepatitis if exposed over the age of 50. Chronic hepatitis B in some regions is now predominantly of the so-called precore mutant type where high levels of HBV replication persist in the presence of anti-hepatitis B virus (HBe) antibodies. The HBV vaccination is among the most cost-effective health care measures. The epidemiological significance of mutations found increasingly in the HBV S gene isolated from vaccinated children is unclear. Evidence that hepatitis G and TT virus are significant causes of hepatitis is lacking. Of interest, however, is the finding that the related GBV-B agent of monkeys may be a model for developing new antiviral agents against HCV. Animal models of hepatitis infections are providing new insights into the pathogenesis of hepatitis in humans. Indeed it is possible that hepatitis E is primarily an agent of pigs and other domesticated livestock. Intriguingly, the new TT virus shares many properties with the circoviruses, significant pathogens of chickens and pigs. The challenge in the next decade will be to assess the significance of these new agents in terms of public health and resources. Value judgements will have to be made in assessing the risks associated with blood containing trace amounts of these adventitious agents.

Animals↗
PubMed1985

[Morphology of adult and sub-adult Wuchereria bancrofti. Differential characteristics among the strains].

The description of the fourth stage larva of W. bancrofti provides an indication of the direction of morphological evolution in the genus showing in particular that W. kalimantani is more highly evolved than W. bancrofti and constitutes a "capture" by Presbytis of the species parasitic in man. No morphological character of adult W. bancrofti distinguishes the geographic origin of the different collections studied. By contrast, the morphological characters of the microfilariae and their biological features are significantly different, but are not inter-correlated. It therefore appears that in the genus Wuchereria, as in the other viviparous filarioids, the phenomenon of speciation is evident first of all in the morphology of the microfilaria, the stage most susceptible to selection pressures.

Aging↗
PubMed1986

[Discovery of a protist parasite, apparently akin to Acrasiae, in the genital tract and various organs of primates].

Microcysts were first observed in histological sections of the placenta of a gibbon, the uterus of a Microcebus, showing a pyometra, the placenta, spleen and lung of a new born mangabey which died soon after birth from an interstitial pneumonia. Plasmodial forms were also discovered in the sections, either encysted or infiltrating the tissues. Cultures from all the above mentioned pathological material were attempted on a special medium, the composition of which will be given later. All cultures shew myxamoeba-like organisms aggregating and merging into pseudoplasmodial forms that produced microcysts. Attention is drawn to the pathogenic rôle of this new kind of parasites in order that they should be searched for, in every case of genital troubles not ascribable to other causes.

Animals↗
PubMed2000

DNA of nonhuman primates harbors hepatitis C-virus-specific sequences of its 5'-non-coding region (5'-NCR).

The DNA from PBMCs of both hepatitis C virus (HCV)-positive patients and healthy HCV-negative human individuals tested thus far contains essential parts--up to 272/341 nucleotides--of the HCV 5'-non-coding region (5'-NCR). These findings bring up the question of the possible evolutionary background of these sequences. Therefore, using the same methodology, we looked for the same sequences in animals closely related to man, i.e., in nonhuman primates (two chimpanzees, one orang-utan, one Debrazza monkey, two New World monkey species and a prosimian). The DNA from PBMCs of the studied animals belonging to nonhuman primates contains essential parts--up to 272/341 nucleotides--of the HCV 5'-non-coding region (5'-NCR). A common sequence of 82 nucleotides is contained in the DNA of all the tested animals but only the chimpanzee's DNA harbors the same, longer sequence region of 272/341 nucleotides of the 5'-NCR found in human DNA. The results may provide a clue as to the possible origin of parts of the IRES containing sequence area of the HCV.

Animals↗
PubMed2004

Genomic data support the hominoid slowdown and an Early Oligocene estimate for the hominoid-cercopithecoid divergence.

Several lines of indirect evidence suggest that hominoids (apes and humans) and cercopithecoids (Old World monkeys) diverged around 23-25 Mya. Importantly, although this range of dates has been used as both an initial assumption and as a confirmation of results in many molecular-clock analyses, it has not been critically assessed on its own merits. In this article we test the robusticity of the 23- to 25-Mya estimate with approximately 150,000 base pairs of orthologous DNA sequence data from two cercopithecoids and two hominoids by using quartet analysis. This method is an improvement over other estimates of the hominoid-cercopithecoid divergence because it incorporates two calibration points, one each within cercopithecoids and hominoids, and tests for a statistically appropriate model of molecular evolution. Most comparisons reject rate constancy in favor of a model incorporating two rates of evolution, supporting the "hominoid slowdown" hypothesis. By using this model of molecular evolution, the hominoid-cercopithecoid divergence is estimated to range from 29.2 to 34.5 Mya, significantly older than most previous analyses. Hominoid-cercopithecoid divergence dates of 23-25 Mya fall outside of the confidence intervals estimated, suggesting that as much as one-third of ape evolution has not been paleontologically sampled. Identifying stem cercopithecoids or hominoids from this period will be difficult because derived features that define crown catarrhines need not be present in early members of these lineages. More sites that sample primate habitats from the Oligocene of Africa are needed to better understand early ape and Old World monkey evolution.

Animals↗
PubMed2006

Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5alpha.

Retroviral restriction factor TRIM5alpha exhibits a high degree of sequence variation among primate species. It has been proposed that this diversity is the cumulative result of ancient, lineage-specific episodes of positive selection. Here, we describe the contribution of within-species variation to the evolution of TRIM5alpha. Sampling within two geographically distinct Old World monkey species revealed extensive polymorphism, including individual polymorphisms that predate speciation (shared polymorphism). In some instances, alleles were more closely related to orthologues of other species than to one another. Both silent and nonsynonymous changes clustered in two domains. Functional assays revealed consequences of polymorphism, including differential restriction of a small panel of retroviruses by very similar alleles. Together, these features indicate that the primate TRIM5alpha locus has evolved under balancing selection. Except for the MHC there are few, if any, examples of long-term balancing selection in primates. Our results suggest a complex evolutionary scenario, in which fixation of lineage-specific adaptations is superimposed on a subset of critical polymorphisms that predate speciation events and have been maintained by balancing selection for millions of years.

Alleles↗
PubMed2003

Relaxed selective pressure on an essential component of pheromone transduction in primate evolution.

The vomeronasal organ (VNO) detects pheromones in many vertebrate species but is likely to be vestigial in humans. TRPC2(TRP2), a gene that is essential for VNO function in the mouse, is a pseudogene in humans. Because TRPC2 is expressed only in the VNO, the loss of selective pressure on this gene can serve as a molecular marker for the time at which the VNO became vestigial. By analyzing sequence data from the TRPC2 gene of 15 extant primate species, we provide evidence that the VNO was most likely functional in the common ancestor of New World monkeys and Old World monkeys and apes, but then became vestigial in the common ancestor of Old World monkeys and apes. We propose that, at this point in evolution, other modalities, notably the development of color vision, may have largely replaced signaling by pheromones.

Amino Acid Sequence↗
PubMed2002

Paranasal sinus anatomy of Aegyptopithecus: implications for hominoid origins.

The East African Early Miocene apes, or proconsulids, have often been considered to be among the earliest members of the Hominoidea, as defined by the divergence of the Cercopithecoidea, but this hypothesis is only weakly supported by available fossil evidence. The ethmofrontal sinus is one of a few morphological features that may link proconsulids with later hominoids. Here we present direct evidence of an ethmofrontal sinus in an early Oligocene stem catarrhine, Aegyptopithecus zeuxis. The presence of this sinus in Aegyptopithecus suggests that its presence in proconsulids is most likely to be a retained primitive condition. The morphological evidence bearing on proconsulids' purported hominoid affinities is further weakened by this conclusion, and alternative phylogenetic possibilities, such as the placement of proconsulids as stem catarrhines are considered more likely.

Animals↗
PubMed2003

Adaptive evolution of cytochrome c oxidase subunit VIII in anthropoid primates.

Cytochrome c oxidase (COX) is a 13-subunit protein complex that catalyzes the last step in mitochondrial electron transfer in mammals. Of the 10 subunits encoded by nuclear DNA (three are mtDNA products), some are expressed as tissue- and/or development-specific isoforms. For COX subunit VIII, previous work showed that expression of the contractile muscle-specific isoform gene, COX8H, is absent in humans and Old World monkeys, and the other isoform gene, COX8L, is expressed ubiquitously. Here, we show that COX8H is transcribed in most primate clades, but its expression is absent in catarrhines, that is, in Old World monkeys and hominids (apes, including humans), having become a pseudogene in the stem of the catarrhines. The ubiquitously expressed isoform, COX8L, underwent nonsynonymous rate acceleration and elevation in the ratio of nonsynonymous/synonymous changes in the stem of anthropoid primates (New World monkeys and catarrhines), possibly setting the stage for loss of the heart-type (H) isoform. The most rapidly evolving region of VIII-L is one that interacts with COX I, suggesting that the changes are functionally coadaptive. Because accelerated rates of nonsynonymous substitutions in anthropoids such as observed for COX8L are also shown by genes for at least 13 other electron transport chain components, these encoded amino acid replacements may be viewed as part of a series of coadaptive changes that optimized the anthropoid biochemical machinery for aerobic energy metabolism. We argue that these changes were linked to the evolution of an expanded neocortex in anthropoid primates.

Amino Acid Sequence↗