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At least 1,297 records · Page 72Linked to original sources
PubMed1992

Allelic diversity at the primate major histocompatibility complex DRB6 locus.

The HLA-DRB6 gene (also called DRB sigma/V1) has been found only in about 26% of human HLA haplotypes, i.e.; DR1, DRw10, and DR2-bearing ones (Corell et al. 1991). In contrast, exon-2 DRB6 sequences have been obtained from all tested primates: nine chimpanzees (Pan troglodytes), three gorillas (Gorilla gorilla) and three orangutans (Pongo pygmaeus); other apes which had already been sequenced (one gorilla and one chimpanzee) also had the DRB6 gene. Thus, all apes tested from three different species, some of them evolutionary separated by at least 14-16 million years, bear the DRB6 gene. In addition, more than one gene copy per haplotype has been found in one chimpanzee; this, together with the apparent loss of this gene in some of the human DR haplotypes, may indicate that the DR genome has undergone evolutionary changes more recently and more actively than class I or III genes. In addition, ten different and presumably allelic DRB6 exon-2 sequences have been obtained, and some of them coming from different species are more similar to each other than the one from the same species; this finding goes in favor of the trans-species theory of major histocompatibility complex polymorphism generation. Also, data are presented supporting that DRB6 may be one of the eldest genes of the DRB family, thus one of the first to diverge from the ancestral DRB gene.

Alleles↗
PubMed1987

Primate evolution of a dispersed human repetitive DNA sequence.

A dispersed middle repetitive DNA sequence isolated originally from human chromosome 12 did not show homology with rodent DNA under standard conditions of Southern DNA blot analysis. The evolutionary relationship of this human repetitive DNA to that of other primates was investigated using three hybridization methods: DNA dot blot, Southern DNA blot analysis, and chromosome in situ hybridization. Homology with the human repetitive DNA was found throughout the suborder Anthropoidea, in fourteen ape and New and Old World monkey species. In addition, the human pattern of hybridization to noncentromeric regions of all chromosomes was seen. No hybridization by any of the three techniques was found in five species of the suborder Prosimii. The phenomenon of marked differences in sequence homology and copy number of dispersed repetitive DNA from closely related species has been observed in protozoans (Plasmodia), Drosophila, sea urchins, mice and the great apes (Hominoidea). We report here a similar phenomenon that may have occurred at an early stage in primate evolution.

Animals↗
PubMed1995

Evolution of a repeat sequence in the parathyroid hormone-related peptide gene in primates.

A polymorphism of the variable number of tandem repeat (VNTR) type is located 97 bp downstream of exon VI of the parathyroid hormone-related peptide (PTHrP) gene in humans. The repeat unit has the general sequence G(TA)nC, where n equals 4-11. In order to characterize the evolutionary history of this VNTR, we initially tested for its presence in 13 different species representing four main groups of living primates. The sequence is present in the human, great apes, and Old World monkeys, but not in New World monkeys; and this region failed to PCR amplify in the Loris group. Thus, the evolution of the sequence as part of the PTHrP gene started at least 25-35 millions years ago, after divergence of the Old World and New World monkeys, but before divergence of Old World monkeys and great apes and humans. The structural changes occurring during evolution are characterized by a relatively high degree of sequence divergence. In general, the tandem repeat region tends to be longer and more complex in higher primates with the repeat unit motifs all being based on a TA-dinucleotide repeat sequence. Intra-species variability of the locus was demonstrated only in humans and gorilla. The divergence of the TA-dinucleotide repeat sequence and the variable mutation rates observed in different primate species are in contrast to the relative conservation of the flanking sequences during primate evolution. This suggests that the nature of the TA-dinucleotide repeat sequence, rather than its flanking sequences, is responsible for generating variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1984

Problems and pitfalls in estimating average pharmacokinetic parameters.

The problems of obtaining optimal average parameter estimates (APE) from experimental pharmacokinetic data are considered. Four different approaches, three parametric and one non-parametric tests, are compared, using selected individual alcohol concentration data. Pooling the raw data for estimating APE can obscure individual pharmacokinetic characteristics, whereas averaging individual parameter estimates (IPE) exposes unique statistical problems. Furthermore, careful consideration should be given to weighting procedures. The advantages and shortcomings of all four methods are discussed. It is concluded that none can be considered as a universally applicable statistical method in view of the purpose for which the information, derived from a set of data, e.g. an alcohol-kinetic study, is required.

Computers↗
PubMed1994

The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary.

Fluorescence in situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescence in situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata and Cercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines.

Animals↗
PubMed1986

The assessment of gas exchange by automated analysis of O2 and CO2 alveolar to arterial differences.

A computer program to measure breath by breath alveolar pressure (PA) and alveolar to arterial difference (AaD) for O2 and CO2, by a mass-spectrometer has been implemented. The program allows the determination of alveolar gas by different methods: 1. Bohr's equation (BE); 2. ideal alveolar air equation for O2 (IDO2); 3. end-tidal (ET); 4. by the Rahn's definition of 'mean alveolar gas', i.e., alveolar pressures are defined when instantaneous respiratory exchange ratio (IRQ) equals mean respiratory exchange ratio (MRQ). This automated technique has been used in 16 patients with chronic obstructive lung disease (COLD) and 15 patients with pulmonary embolism (APE). In both groups of patients it was always possible to find in each breath the point where IRQ = MRQ and therefore to measure AaD by RD. IDO2 was significantly lower than PAO2 by the other methods. Also ET values of O2 and CO2 were significantly different from RD and BE in both groups of patients, however the difference was consistently higher in COLD patients. The different shape of the expirograms (steeper expirograms in COLD) is responsible for this different result. RD and BE AaD characterize gas exchange more precisely than ET, because the contribution of high VA/Q units is also evaluated. This is particularly important in COLD patients. Consideration on dead space measurements are also reported both for COLD and APE patients. In conclusion this automated technique provides the assessment of gas exchange for the use in clinical respiratory physiology and for the monitoring of gas-exchange in critically ill patients.

Aged↗
PubMed1987

Man's place in Hominoidea as inferred from molecular clocks of DNA.

Divergence dates among primates were estimated by molecular clock analysis of DNA sequence data. A molecular clock of eta-globin pseudogene was calibrated by setting the date of divergence between Catarrhini and Platyrrhini at 38 million years (Myr) ago. The clock gave dates of 25.3 +/- 2.4, 11.9 +/- 1.7, 5.9 +/- 1.2, and 4.9 +/- 1.2 Myr ago ( +/- refers to standard error) for the separation of rhesus monkey, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. In placing confidence intervals of the estimates in a robust way, a bootstrap method was used. The 95% confidence intervals are 20.5-29.5, 9.0-14.8, 4.1-7.8, and 3.1-7.0 Myr ago for the separation of rhesus monkey, orangutan, gorilla, and chimpanzee, respectively. By a molecular clock dating of the Prosimii-Anthropoidea splitting, it was suggested that the evolutionary rate of the eta-globin gene was high early in primate evolution and subsequently decreased in the line of Anthropoidea. And, by a relative rate test using bootstrap sampling, the possibility of further decrease of the rate (more than 10%) in the line of Hominoidea compared with that of Cercopithecoidea was suggested. Therefore, the above dating of the splittings within Hominoidea may be biased slightly toward younger dates. On the other hand, mitochondrial DNA (mtDNA) seems to have evolved in mammals with a more uniform rate than the eta-globin gene. The ratio of the dates of orangutan splitting to chimpanzee splitting is larger for the mtDNA clock than that for the eta-globin clock, suggesting the possibilities of mtDNA introgression among the early hominids and the early African apes, and/or of mtDNA polymorphism within the common ancestral species of orangutan and the African apes that obscures the date of the true species separation of orangutans.

Animals↗
PubMed1996

Comparative fluorescence in situ hybridization mapping of primate chromosomes with Alu polymerase chain reaction generated probes from human/rodent somatic cell hybrids.

We have used Alu polymerase chain reaction generated probes from rearranged human/rodent somatic cell hybrids for fluorescence in situ hybridization and comparative mapping of some intrachromosomal changes in the karyotypes of great apes (Pan troglodytes, P. paniscus, Gorilla gorilla, Pongo pygmaeus), a gibbon (Hylobates lar), and an Old World monkey (Macaca fuscata). Probes containing chromosomes 2 and 18 fragments confirmed inversions already suggested by the banding pattern of great ape homologues. However, a chromosome 3 fragment showed complex rearrangements in the gibbon and macaque karyotype which were previously not well defined from banding. 'Subchromosomal painting' will allow the identification of intrachromosomal changes on the basis of DNA homology and provides a powerful method to study karyological and genomic evolution.

Animals↗
PubMed1996

Analysis of the organisation and localisation of the FSHD-associated tandem array in primates: implications for the origin and evolution of the 3.3 kb repeat family.

The D4Z4 locus is a polymorphic tandem repeat sequence on human chromosome 4q35. This locus is implicated in the neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD). The majority of sporadic cases of FSHD are associated with de novo DNA deletions within D4Z4. However, it is still not known how this rearrangement causes FSHD. Although the repeat contains homeobox sequences, despite exhaustive searching, no transcript from this locus has been identified. Therefore, it has been proposed that the deletion may invoke a position effect on a nearby gene. In order to try to understand the role of the D4Z4 repeat in this disease, we decided to investigate its conservation in other species. In this study, the long-range organisation and localisation of loci homologous to D4Z4 were investigated in primates using Southern blot analysis, pulsed field gel electrophoresis and fluorescence in situ hybridisation. In humans, probes to D4Z4 identify, in addition to the 4q35 locus, a closely related tandem repeat at 10qter and many related repeat loci mapping to the acrocentric chromosomes; a similar pattern was seen in all the great apes. In Old World monkeys, however, only one locus was detected in addition to that on the homologue of human chromosome 4, suggesting that the D4Z4 locus may have originated directly from the progenitor locus. The finding that tandem arrays closely related to D4Z4 have been maintained at loci homologous to human chromosome 4q35-qter in apes and Old World monkeys suggests a functionally important role for these sequences.

Animals↗
PubMed1992

Alteration in mouse splenic phospholipid fatty acid composition and lymphoid cell populations by dietary fat.

The fatty acid composition of diacyl- and alkylacylglycerophosphocholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), alkenylacyl-glycerophosphoethanolamine (aPE), and diacyl- and alkylacyl-glycerophosphoethanolamine (dPE) was assessed in isolated splenocytes from C3H/Hen mice fed one of four purified isocaloric diets for six weeks. Diets contained 20% by weight of either a high-linoleate sunflower oil (Hi 18:2), a high-oleate sunflower oil (Hi 18:1), a mixture of 17% menhaden fish oil and 3% high-linoleate sunflower oil (Hi n-3), or a mixture of 17% coconut oil and 3% high-linoleate sunflower oil (Hi SFA). Spleen weight and immune cell yield were significantly higher (P less than 0.05) in mice fed the Hi 18:1 or the Hi n-3 diets compared with those fed the Hi 18:2 and Hi SFA diets. Distinctive patterns of fatty acids were observed for each phospholipid in response to dietary fatty acids. Dietary fat significantly affected (P less than 0.05) total polyunsaturated fatty acids (PUFA) in PC and dPE, total saturated fatty acids (SFA) in PC, total monounsaturated fatty acids (MUFA), and n-3 PUFA in all phospholipid classes examined. In mice fed the Hi n-3 diet, n-3 PUFA were significantly elevated, whereas n-6 PUFA decreased in all of the phospholipids. In these mice, eicosapentaenoic acid (EPA) was the predominant n-3 PUFA in PC and PI, whereas docosahexaenoic acid (DHA) was the major n-3 PUFA in aPE and PS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evolution of four human Y chromosomal unique sequences.

Four cloned unique sequences from the human Y chromosome, two of which are found only on the Y chromosome and two of which are on both the X and Y chromosomes, were hybridized to restriction enzyme-treated DNA samples of a male and a female chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), and pig-tailed macaque (Macaca nemestrina); and a male orangutan (Pongo pygmaeus) and gibbon (Hylobates lar). One of the human Y-specific probes hybridized only to male DNA among the humans and great apes, and thus its Y linkage and sequence similarities are conserved. The other human Y-specific clone hybridized to male and female DNA from the humans, great apes, and gibbon, indicating its presence on the X chromosome or autosomes. Two human sequences present on both the X and Y chromosomes also demonstrated conservation as indicated by hybridization to genomic DNAs of distantly related species and by partial conservation of restriction enzyme sites. Although conservation of Y linkage can only be demonstrated for one of these four sequences, these results suggest that Y-chromosomal unique sequence genes do not diverge markedly more rapidly than unique sequences located on other chromosomes. However, this sequence conservation may in part be due to evolution while part of other chromosomes.

Animals↗
PubMed1997

Acetylcholine-induced vasoconstrictor response of coronary vessels in rats: a possible contribution of M2 muscarinic receptor activation.

A mechanism by which acetylcholine (ACh) may elicit vasoconstrictor response in coronary vessels was studied in rat hearts perfused at a constant flow rate. In spontaneously beating hearts, bolus injections of ACh and carbachol (CCh) produced biphasic changes in coronary perfusion pressure (CPP): a transient increase at the initial period followed by a sustained decrease. In KCl-arrested hearts, ACh and CCh produced a monophasic increase in CPP, which was attenuated by either removal of endothelial cells by saponin or cyclooxygenase inhibition by diclofenac sodium. In the spontaneously beating heart, ACh-induced vasoconstriction was almost abolished by atropine (0.1 microM) and was markedly attenuated by an M2 antagonist, methoctramine (0.1 microM), but not by an M1 antagonist, pirenzepine (1 microM). Arecaidine propargyl ester (APE), an M2 agonist, produced coronary artery constriction which was attenuated by methoctramine (0.1 microM) but not by pirenzepine (0.1 microM) in both spontaneously beating and KCl-arrested hearts. McN-A-343, an M1 agonist, increased CPP in both beating and KCl-arrested hearts, but to a lesser degree than APE. These results suggest that the release of vasoconstrictor prostaglandins from endothelial cells contributes to the vasoconstrictor response to ACh in perfused rat coronary vessels, and the response to ACh appears to be mediated, in part, via the M2 subtype of muscarinic receptors.

Acetylcholine↗
PubMed1997

Characterization of postjunctional muscarinic receptors mediating contraction in rat anococcygeus muscle.

The present study was designed to characterize the postjunctional muscarinic receptors mediating contraction in rat anococcygeus muscle by means of a series of muscarinic agonists and subtype-preferring key muscarinic antagonists. Cumulative addition of muscarinic agonists elicited concentration-dependent contractions with the following rank order of potency (pD2 values): (+)-muscarine (6.36) > or = oxotremorine M (6.21) > or = arecaidine propargyl ester (APE) (6.18) > carbachol (5.68) = (+/-)-methacholine (5.65) > 4-(4-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium chloride (4-Cl-McN-A-343) (4.28) > 4-(3-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) (3.89). (+)-Muscarine, oxotremorine M, carbachol and (+/-)-methacholine behaved as full agonists, whereas APE, 4-Cl-McN-A-343 and McN-A-343 displayed partial agonism. The contractile responses of the rat anococcygeus muscle to (+/-)-methacholine were competitively antagonized by pirenzepine (pA2 = 6.92), 11-[[4-[4-(diethylamino)butyl]-1-piperidinyl]acetyl] 5,11-dihydro-6H-pyrido(2,3-b) (1,4)-benzodiazepine-6-one (AQ-RA 741; pA2 = 6.75), himbacine (pA2 = 7.11), (+/-)-p-fluoro-hexahydro-sila-difenidol (p-F-HHSiD; pA2 = 7.68) and the (R)- and (S)-enantiomers of hexahydro-difenidol [(R)-HHD: pA2 = 8.52; (S)-HHD: pA2 = 6.06]. A comparison of the pA2 values derived from studies of contraction in rat anococcygeus muscle with literature binding (pKi values) and functional affinities (pA2 values) obtained at native M1-M4 receptors strongly suggests that the postjunctional muscarinic receptors mediating contraction in rat anococcygeus muscle are of the M3 subtype.

Animals↗
PubMed2002

A revised evolutionary history of hepatitis B virus (HBV).

Previous studies of the evolutionary history of hepatitis B virus (HBV) have been compromised by intergenotype recombination and complex patterns of nucleotide substitution, perhaps caused by differential selection pressures. We examined the phylogenetic distribution of recombination events among human HBV genotypes and found that genotypes A plus D, and genotypes B plus C, had distinct patterns of recombination suggesting differing epidemiological relationships among them. By analyzing the nonoverlapping regions of the viral genome we found strong bootstrap support for some intergenotypic groupings, with evidence of a division between human genotypes A-E from the viruses sampled from apes and human genotype F. However, the earliest events in the divergence of HBV remain uncertain. These uncertainties could not be explained by differential selection pressures, as the ratio of nonsynonymous-to-synonymous substitutions ( d(N)/ d(S)) did not vary extensively among lineages and there is no strong evidence for positive selection across the whole tree. Finally, we provide a new estimate of the mean substitution rate in HBV, 4.2 x 10(-5), which suggests that divergence of HBV in humans and apes has occurred only in the last 6000 years.

Animals↗
PubMed2004

Comparative analysis of Alu insertion sequences in the APP 5' flanking region in humans and other primates.

Overexpression of the amyloid precursor protein gene (APP) may play a role in the neuropathology of Alzheimer's disease. Therefore, elucidating the mechanisms involved in APP gene regulation is of primary importance, and various cis-acting regulatory elements located in 5' distal regions are known to play a main role. Some of them lie within Alu elements, one of which (Alu1) is only found in humans and apes while the other (Alu2) has a much older history and is also found in rhesus. These Alu insertions harbor sequence motifs that may act as cis-regulatory elements, which may cause differences in APP regulation among primate species and whose functionality may be ascertained through their conservation in a comparative analysis. We have performed a comparative analysis of the region comprising the two Alu elements of the APP promoter in several primates, including humans. We have found a significant decrease in nucleotide diversity in the Alu2 element (inserted in all the species analyzed) compared to the Alu1 (inserted only in apes). This finding can be interpreted as a constriction in the Alu2 sequence variation as a consequence of a functional role of this element in the APP expression. The present results suggest a wider extension of the regulatory elements than the known short consensus regulatory sequences. Moreover, the different conservation of two highly similar and neighboring sequences suggests that, besides the importance of the sequence motifs, their position in relation to the gene suggests that they have played a role in being recruited as regulatory elements.

5' Flanking Region↗
PubMed2002

Beta-defensin 1 gene variability among non-human primates.

Defensins are a recently described family of peptides that play an important role in innate immunity. Recent studies have shown that defensins exhibit a broad spectrum of antimicrobial activities against bacteria and fungi. Three families have been identified so far in mammals, alpha-defensins, beta-defensins and theta-defensins, presumably derived from a common ancestral defensin. A long-term study on the evolution of these multigene families among primates has been undertaken to investigate: (1) the degree of interspecific differentiation; (2) the genetic mechanisms responsible for the variability of these molecules; and (3) the possible role of different environmental factors in their evolution. Nucleotide sequences have been obtained from great and lesser apes, several African and Asian catarrhine monkeys and one New World monkey. A comparison of rates of synonymous and nonsynonymous (amino-acid changing) nucleotide substitution indicates that the primate beta-defensin 1 gene evolved under a pattern of random nucleotide substitution as predicted by the neutral theory of molecular evolution. These results are not consistent with the hypothesis that the primate beta-defensin 1 gene has diversified in response to changes in the microbial species to which a given host is exposed. Analyses of interpecific variability have yielded some insights about the pattern of molecular evolution of the gene among primates. Humans and great apes present high levels of sequence similarity, differing in only one amino acid residue in the mature peptide. Compared with these taxa, hylobatids and cercopithecids exhibit 3-4 amino acid substitutions, some of which increase the net charge of the active molecule.

Animals↗
PubMed2006

Evolution of an intronic microsatellite polymorphism in Toll-like receptor 2 among primates.

Nonhuman primates express varying responses to Mycobacterium tuberculosis: New World monkeys appear to be resistant to tuberculosis (TB) while Old World monkeys seem to be particularly susceptible. The aim of this study was to elucidate the presence of the regulatory guanine-thymine (GT) repeat polymorphisms in intron 2 of Toll-like receptor 2 (TLR2) associated with the development of TB in humans and to determine any variations in these microsatellite polymorphisms in primates. We sequenced the region encompassing the regulatory GT repeat microsatellites in intron 2 of TLR2 in 12 different nonhuman primates using polymerase chain reaction amplification, TA cloning, and automatic sequencing. The nonhuman primates included for this study were as follows: chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), Celebes ape (Macaca nigra), rhesus monkey (Macaca mulatta), pigtail macaque (Macaca nemestrina), patas monkey (Erythrocebus patas), spider monkey (Ateles geoffroyi), Woolly monkey (Lagothrix lagotricha), tamarin (Saguinus labiatus), and ring-tailed lemur (Lemur catta). Nucleotide sequences encompassing the regulatory GT repeat region are similar across species and are completely conserved in great apes. However, Old World monkeys lack GT repeats altogether, while New World monkeys and ring-tailed lemurs have much more complex structures around the position of the repeats. In conclusion, the genetic structures encompassing the regulatory GT repeats in intron 2 of human TLR2 are similar among nonhuman primates. The sequence is most conserved in New World monkeys and less in Old World monkeys.

Animals↗
PubMed1999

Evidence for an HLA-C-like locus in the orangutan Pongo pygmaeus.

HLA-B and C are related class I genes which are believed to have arisen by duplication of a common ancestor. Previous study showed the presence of orthologues for both HLA-B and C in African apes but only for HLA-B in Asian apes. These observations suggested that the primate C locus evolved subsequent to the divergence of the Pongidae and Hominidae. From an analysis of orangutan Tengku two HLA-C-like alleles (Popy C*0101 and Popy C*0201) were defined as well as three HLA-B-like (Popy-B) alleles. By contrast, no Popy-C alleles were obtained from orangutan Hati, although three Popy-B alleles were defined. Thus an HLA-C-like locus exists in the orangutan (as well as a duplicated B locus), implying that the primate C locus evolved prior to the divergence of the Pongidae and Hominidae and is at least 12-13 million years old. Uncertain is whether all orangutan MHC haplotypes contain a C locus, as the failure to find C alleles in some individuals could be due to a mispairing of HLA-C-specific primers with certain Popy-C alleles. These results raise the possibilities that other primate species have a C locus and that the regulation of natural killer cells by C allotypes evolved earlier in primate evolution than has been thought.

Alleles↗