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The rates of molecular evolution in rodent and primate mitochondrial DNA.

A higher rate of molecular evolution in rodents than in primates at synonymous sites and, to a lesser extent, at amino acid replacement sites has been reported previously for most nuclear genes examined. Thus in these genes the average ratio of amino acid replacement to synonymous substitution rates in rodents is lower than in primates, an observation at odds with the neutral model of molecular evolution. Under Ohta's mildly deleterious model of molecular evolution, these observations are seen as the consequence of the combined effects of a shorter generation time (driving a higher mutation rate) and a larger effective population size (resulting in more effective selection against mildly deleterious mutations) in rodents. The present study reports the results of a maximum-likelihood analysis of the ratio of amino acid replacements to synonymous substitutions for genes encoded in mitochondrial DNA (mtDNA) in these two lineages. A similar pattern is observed: in rodents this ratio is significantly lower than in primates, again consistent only with the mildly deleterious model. Interestingly the lineage-specific difference is much more pronounced in mtDNA-encoded than in nuclear-encoded proteins, an observation which is shown to run counter to expectation under Ohta's model. Finally, accepting certain fossil divergence dates, the lineage-specific difference in amino acid replacement-to-synonymous substitution ratio in mtDNA can be partitioned and is found to be entirely the consequence of a higher mutation rate in rodents. This conclusion is consistent with a replication-dependent model of mutation in mtDNA.

Animals↗

Extensive Mhc-DQB variation in humans and non-human primate species.

Non-human primates are often used in biomedical research, and the application of these animals as a model in immune-related diseases necessitates the characterisation of their MHC system. In particular, the MHC class II regions of the chimpanzee (Pan troglodytes), the rhesus macaque (Macaca mulatta)and the common marmoset (Callithrix jacchus) have been subject of molecular biological studies in recent years. In this study the emphasis was on MHC class II genes of another macaque species, Macaca fascicularis(crab eating macaque or cynomolgous monkey). The exon 2 of the Mhc-DQB gene (Mafa-DQB) was sequenced in each of a random panel of 60 non-pedigreed cynomolgous monkeys. This resulted in the detection of 23 Mafa-DQB1alleles that had not previously been published. In addition, unreported alleles were found in chimpanzees, rhesus macaques, orang-utans (Pongo pygmaeus) and stump-tailed macaques (Macaca arctoides), of which a few individuals were included in this study. Phylogenetic analyses confirm the trans-species model of evolution of the MHC-DQBlineages, in which a group of major alleles is passed on in the phylogeny, and has led to the sharing of allelic lineages by different species of non-human primates. The sharing of alleles is observed only for closely related macaque species. Furthermore, this manuscript provides an overview of all published, and whenever necessary corrected, non-human primate Mhc-DQB exon 2 alleles.

Alleles↗

Comparison of allele O sequences of the human and non-human primate ABO system.

Like humans, non-human primates express the antigens A and B of the ABO histoblood group system. In chimpanzees, only A and O types are found, while the types A, B, AB, and O are found in macaques. The sequences of exons 6 and 7 of two chimpanzee O alleles (Odel and O(x), two macaque species O alleles (rhesus monkey and crab-eating macaque), and sequences of exon 7 of two major chimpanzee A alleles (A1ch and A2ch) were established. The sequences of cDNAs corresponding to the chimpanzee and rhesus monkey O alleles were characterized from exon 1 to 7 and from exon 4 to 7, respectively. A comparison of our results with ABO gene sequences already published by others demonstrates that human and non-human primate O alleles are species-specific and result from independent silencing mutations. These observations reinforce the hypothesis that the maintenance of the ABO gene polymorphism in primates reflects convergent evolution more than transpecies inheritance of ancestor alleles.

ABO Blood-Group System↗

Rapid nonsynonymous evolution of the iron-sulfur protein in anthropoid primates.

Cytochrome c (CYC) and 9 of the 13 subunits of cytochrome c oxidase (complex IV; COX) were previously shown to have accelerated rates of nonsynonymous substitution in anthropoid primates. Cytochrome b, the mtDNA encoded subunit of ubiquinol-cytochrome c reductase (complex III), also showed an accelerated nonsynonymous substitution rate in anthropoid primates but rate information about the nuclear encoded subunits of complex III has been lacking. We now report that phylogenetic and relative rates analysis of a nuclear encoded catalytically active subunit of complex III, the iron-sulfur protein (ISP), shows an accelerated rate of amino acid replacement similar to cytochrome b. Because both ISP and subunit 9, whose function is not directly related to electron transport, are produced by cleavage into two subunits of the initial translation product of a single gene, it is probable that these two subunits of complex III have essentially identical underlying rates of mutation. Nevertheless, we find that the catalytically active ISP has an accelerated rate of amino acid replacement in anthropoid primates whereas the catalytically inactive subunit 9 does not.

Amino Acid Sequence↗

The Enterobiinae subfam. Nov. (Nematoda, Oxyurida) pinworm parasites of primates and rodents.

Recent redescriptions of most members of the Oxyuridae Cobbold, 1864 parasitic in primates revealed that they share following derived characters: sexual dimorphism of lateral alae (single-crested in the males, double-crested in the females); in males a second pair of genital papillae always surrounded by strongly cuticularized rings; in females, uterine tube divided into 2 parts by a cellular wall forming a diaphragm. These characters are interpreted as synapomorphies, providing evidence that these taxa represent a monophyletic group, and we propose to classify them in a new subfamily of the Oxyuridae: the Enterobiinae subfam.nov. The Enterobiinae as recognized herein occurs in both Old World and New World Primates and rodents of the family Sciuridae (tribe Sciurini in the Holarctic region and tribe Xerini in the Ethiopian region). The new subfamily includes the following genera: Enterobius Leach, 1853; Colobenterobius Quentin, Betterton & Krishnasamy, 1979; Rodentoxyuris Quentin & Tenora 1974; Xeroxyuris Hugot, 1995; Lemuricola Chabaud & Petter, 1959; Protenterobius Inglis, 1961; Madoxyuris Chabaud, Brygoo & Petter, 1965; Trypanoxyuris Vevers, 1923; Hapaloxyuris Inglis & Cosgrove, 1965 and Paraoxyuronema Artigas, 1936. The genus Paraoxyuronema is revalidated as a subgenus of Trypanoxyuris due to its specialized buccal structures. This genus groups all pinworm nematodes specific for primates of the family Atelidae, including: P. brachytelesi Artigas, 1937 occurring in Brachyteles arachnoides; P. atelis (Cameron, 1929) occurring in Ateles spp., and P. duplicidens (Buckley, 1931) and P. lagothricis (Buckley, 1931), which are parasites of Lagothrix spp. Inglisoxyuris inglisi Chabaud, Petter & Golvan, 1961, included in the monospecific genus Inglisoxyuris and previously classified as a subgenus of the Lemuricola, does not share the characters of the new subfamily and, until its precise classification can be considered with more information, it is proposed to refer to this species as an Oxyuridae sensu lato. A diagnosis and a key of the genera included in the new subfamily are given.

Animals↗

The primate psi beta 1 gene. An ancient beta-globin pseudogene.

The human beta-globin gene cluster contains five functional genes plus a single pseudogene termed psi beta 1. Hybridization and comparative sequence analysis show that this pseudogene is not the product of a recent gene duplication, but is ancient and has been maintained in all major primate groups ranging from prosimians to anthropoids, at the same position as in man, between gamma- and delta-globin genes. In the lemur, a prosimian, the central exons of the psi beta 1 and delta-globin genes have undergone an unequal exchange, which has resulted in a contraction of the beta-globin gene cluster and the formation of a Lepore-type psi beta 1-delta globin pseudogene. Comparisons of defects shared by prosimian, New World monkey and human psi beta 1 sequences suggest that the ancestral primate gene was probably a pseudogene with an abnormal initiation codon but few if any additional defects, and that most contemporary pseudogene defects were accumulated relatively recently by slow neutral drift. We suggest that psi beta 1 arose early in primate evolution by silencing of a pre-existing discrete functional gene, and show that psi beta 1-related sequences are also present in other mammalian orders. In view of the antiquity of psi beta 1-related sequences, we propose that this gene be renamed the eta-globin gene.

Animals↗

Differences of superoxide production in blood leukocytes stimulated with thymol between human and non-human primates.

Thymol induced superoxide production (O2-) by blood leukocytes was examined in various primates including man. Leukocytes of chimpanzee and hamadryas baboon cells showed only 35% of the maximal O2- production rate obtained in human cells, and those of the Japanese monkey and orang-utan failed to respond. In contrast, when cells were stimulated with 12-O-tetradecanoyl phorbol acetate, no significant difference in the O2- production rate was observed between human and monkey cells except for chimpanzee. These results showed that human leukocytes are the most sensitive to thymol among the primates tested. The responsiveness of non-human primate leukocytes could be classified into two types, African-type(chimpanzee and baboon) and Asian-type(orang-utan and macaque).

Animals↗

The role of the adenylyl cyclase system in the regulation of corpus luteum function in the human and in nonhuman primates.

We have reviewed the properties of luteinizing hormone/human chorionic gonadotropic (LH/hCG)-sensitive adenylyl cyclase (AC) of human corpus luteum (CL) and its regulation by several hormones and nonhormonal activators. We have also described the changes in enzyme activity in membrane preparations of human and cynomolgus monkey CL obtained at various stages of the menstrual cycle and pregnancy. The data have been analyzed with respect to the functional status of the luteal tissue and to the species differences among primate CL. In the menstrual cycle, luteal AC responsiveness to LH/hCG was detectable during the midluteal phase, but not during the late luteal phase or in the follicular phase of the following cycle. In addition, nonhormonal stimulation was high in CL obtained during the midluteal and late luteal phases, but declined drastically by the follicular phase of the next cycle. In early pregnancy, the enzyme was unresponsive to LH/hCG stimulation, yet its sensitivity to nonhormonal stimulation was similar, if not identical, to that of midluteal phase CL. Functional activity was also evident at the end of pregnancy. These results demonstrate that expression of AC activity in primate luteal membrane changes significantly with varying hormonal status under physiologic conditions. It is concluded that the AC system in luteal membranes is an effective model to study the mechanisms that regulate function and life span of the human and nonhuman primate CL.

Adenylyl Cyclases↗

Infant abuse and neglect: lessons from the primate laboratory.

We review the several areas in which research on nonhuman primates contributes to our understanding of child abuse and neglect in human children. One special advantage of primate studies is that the experimental method can be utilized to examine the short- and long-term effects of relatively well-defined and circumscribed alterations in early experience and the manner in which they can affect later behavioral and physiological development. Four studies in M. nemestrina (pigtail) monkeys are described in which relatively short social separation experiences in infancy were associated with evidence of persistent changes in certain aspects of social behavioral functioning and immunological functioning, up to six years later, when the previously separated animals were in late adolescence or early adulthood. Such findings suggest that nonhuman primates may be used as animal model systems with considerable relevance to issues surrounding human child abuse and neglect.

Animals↗

Integrated phylogeny of the primate brain, with special reference to humans and their diseases.

Fossil, comparative anatomic and ontogenic data suggest that several systems of functionally and anatomically related brain regions underwent selective expansion or differentiation during primate evolution, according to the principle of 'integrated phylogeny'. This process was closely tied to expansion of the neocortex, particularly of its association areas. System I regions include the association neocortices as well as the nucleus basalis of Meynert, the entorhinal cortex, and subdivisions of the septum, hippocampal formation and amygdaloid complex. This system undergoes degeneration in Alzheimer's and Pick's diseases and Down syndrome. System II includes segregated circuits involving parts of the frontal cortex, basal ganglia, thalamus, and substantia nigra, and can become defective in obsessive-compulsive disorder, Huntington's and Parkinson's diseases. Certain nuclei in the mesencephalon and brainstem, which co-evolved with System I and II regions, also demonstrate pathology in diseases affecting these systems. Integrated phylogeny of each of these systems during primate evolution likely was promoted by regulatory mutations, gene duplications or chromosomal rearrangements. Thus, understanding the genetic basis of integrated phylogeny of systems of brain regions during primate evolution may elucidate the pathogenesis of the human diseases which affect these regions.

Animals↗

Patterns of integration of exogenous DNA sequences transfected into mammalian cells of primate and rodent origin.

We studied the cotransfer and cointegration of several genes transfected into four cell lines of primate origin. Mouse thymidine-kinase-negative LM cells, which had been extensively studied previously, were used as a reference. We found that in monkey kidney Vero cells, on average between 3.5 and 6.0 kb of plasmid sequences was integrated per clone, while in the murine LM cell line, 9-186 kb of exogenous DNA was integrated per clone. Transformed Vero clones which had integrated more than 6 kb of DNA did not integrate larger DNA fragments in a second transformation assay than had the parental Vero cells. We found that the efficiency of gene cointegration is similar in Vero, HeLa and GM4312A cells, the latter being deficient in the repair of UV-induced damage. The human hepatocarcinoma Hep G2 cells integrated on the average 2 kb more exogenous DNA than the three other primate cell lines, which resulted in a 4-5 times higher efficiency of gene cointegration. Plasmid penetration and persistence in a free state between 24 h and two weeks after transfection was similar in Vero and LM cells. No major post-integration DNA rearrangement could be demonstrated after the isolation of Vero clones. These observations correlate the low efficiency of gene cointegration in some primate cell lines with a genomic recombination step or with rearrangements taking place during early cell divisions following integration.

Animals↗

Nonhuman primates prefer slow tempos but dislike music overall.

Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21] to test cotton-top tamarins and common marmosets, two new-World primates, for their spontaneous responses to stimuli that varied systematically with respect to tempo. Across several experiments, we found that both tamarins and marmosets preferred slow tempos to fast. It is possible that the observed preferences were due to arousal, and that this effect is homologous to the human response to tempo. In other respects, however, these two monkey species showed striking differences compared to humans. Specifically, when presented with a choice between slow tempo musical stimuli, including lullabies, and silence, tamarins and marmosets preferred silence whereas humans, when similarly tested, preferred music. Thus despite the possibility of homologous mechanisms for tempo perception in human and nonhuman primates, there appear to be motivational ties to music that are uniquely human.

Animals↗

Dehydroepiandrosterone-sulfate as a biomarker of senescence in male non-human primates.

Numerous studies have suggested important and varying roles for dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in primate physiological functions. Despite these numerous claims, specific actions and significance of DHEA and DHEA-S are still equivocal. A decline of these hormones in adult humans may have functional significance, yet there is no clear relationship between functional impairments of aging and the decline in DHEA or DHEA-S levels. This current study attempts to address the natural history of adrenal hormones by presenting non-human primate evidence of the endocrinology of aging; the age-related patterns of adrenal hormone decline in three species of the subfamily Cercopithecinae, Macaca mulatta, Macaca nemestrina, and Papio cynocephalus are compared. It is concluded that DHEA-S and cortisol represent lineage specific markers of senescence among primates and that parallel age-related patterns of DHEA-S and cortisol likely reflect lineage specific effects, or rather, phylogenetic similarities of endocrine senescence. The use of relative adrenal hormone levels to approximate species' life expectancies is discussed.

Adrenal Cortex Hormones↗

Evolution of the tandem repeats in thymidylate synthase enhancer region (TSER) in primates.

The upstream regulatory region of the human thymidylate synthase gene (thymidylate synthase enhancer region, TSER) is length polymorphic, attributable to variable numbers of tandemly repeated copies of a 28-bp fragment. It has been found that TSER length polymorphism is correlated to malignancy risk. To further our understanding of the origin and evolution of TSER, this region was investigated among different primates, including hominoids, two subfamilies of the Old World monkeys (OWMs): colobines and cercopithecines, and two species of the New World monkeys (NWMs). In addition to humans, our results show that length polymorphism in TSER is also present in some primate populations, although it appears that this region is length monomorphic in many other primates. We identified three unique repeat motifs in TSER and defined them as R1, R2, and R3, respectively, starting from the 3' end. The same repeat motifs from different species are more similar to each other than different repeat motifs within same species are. Such a paraphyletic pattern suggests that divergence of the three repeat motifs predated divergence of the OWMs/hominoids and the NWMs. The most recent common ancestor (MRCA) of hominoids and the OWMs probably possessed triple repeats but now double and triple repeats are two dominant types in hominoids and the OWMs. In addition, our results show that each of the three repeat motifs may be lost independently. We have also found clues that recombination was involved in formation of tandem repeat polymorphism in TSER.

Alleles↗

Human endogenous retroviral elements belonging to the HERV-S family from human tissues, cancer cells, and primates: expression, structure, phylogeny and evolution.

A new human endogenous retrovirus family (HERV-S) was recently identified from the human chromosome X. The HERV-S was 6.7 kb in length with typical retroviral structure (LTR-gag-pol-env-LTR). We investigated pol fragments of HERV-S family in various human tissues and cancer cells. The pol gene was expressed in only brain and thymus among human tissues (brain, prostate, testis, heart, kidney, liver, lung, placenta, skeletal muscle, spleen, thymus, uterus), whereas the pol gene was detected in various cancer cell lines (RT4, PFSK-1, BT-474, HCT-116, Jurkat, HepG2, MCF7, OVCAR-3, MIA-PaCa-2, PC3, LOX-IMVI, AZ521, 2F7, and C-33A) except for TE-1, UO-31, A549, and U-937 by RT-PCR analysis. Expression and sequencing data of the 33 clones imply that the pol gene of HERV-S family is more active in cancer cells than in human tissues, which may have transcriptional potential role related to various human cancers. Phylogenetic analysis of HERV-S pol family distinctively divided into three groups (group I, II, and III) through evolutionary divergence in primate evolution. Evolutionary divergence of the HERV-S family by PCR amplification and sequence analysis indicated that they were integrated into the primate genomes approximately 43 Myr ago and have been evolved rate of 0.3% nucleotide differences per Myr during primate evolution.

Amino Acid Sequence↗

Sequence evolution, processing, and posttranslational modification of zonadhesin D domains in primates, as inferred from cDNA data.

Zonadhesin is a mammalian transmembrane sperm ligand. Precursor zonadhesin essentially consists of MAM (meprin/A5 antigen/mu receptor tyrosine phosphatase) domains, a mucin-like repeat, and D domains (homologous to von Willebrand D). Recent immunovisualization and binding assays indicate that zonadhesin D domains 1-3 bind postacrosomally to the zona pellucida. This feature has attracted considerable interest in the evolution of zonadhesin and its possible biological and biomedical implications. Previous molecular evolutionary analyses, however, were confined to cDNA sequences of only few distantly related species. Moreover, except for rabbit and pig, little is known about zonadhesin's processing. To delineate the situation in primates including humans, we analyze here the evolution of zonadhesin on the basis of D domain encoding cDNAs of about 4900 base pairs (bp) length from a representative primate sampling (1 Strepsirhini, 3 Cercopithecidae, 3 Platyrrhini, and human; 7 new sequences) plus GenBank data from mouse, rabbit, and pig. Site-specific (CODEML and HyPhy) analysis indicates positive evolution of zonadhesin. Moreover, moving window analysis (CRANN) points to a positive correlation of sequence evolution and sperm-competition. Significant accumulations of positively selected sites across interspecifically variable motifs (identified by PROSITE) suggest that positive selection promotes differences between species by amino acid exchanges and changes in posttranslational modification. In the case of zonadhesin D domains, positive selection might thus contribute to the species-specific binding of zonadhesin and zona pellucida. A high conservation of processing and dimerization motifs of primate zonadhesin in analogy to pig, on the other hand, illustrates that zonadhesin's backbone needs to meet basic requirements in order to retain function.

Amino Acid Sequence↗

Conservative evolution in duplicated genes of the primate Class I ADH cluster.

Humans have seven alcohol dehydrogenase genes (ADH) falling into five classes. Three out of the seven genes (ADH1A, ADH1B and ADH1C) belonging to Class I are expressed primarily in liver and code the main enzymes catalyzing ethanol oxidization. The three genes are tandemly arrayed within the ADH cluster on chromosome 4 and have very high nucleotide similarity to each other (exons: >90%; introns: >70%), suggesting the genes have been generated by duplication event(s). One explanation for maintaining similarity of such clustered genes is homogenization via gene conversion(s). Alternatively, recency of the duplications or some other functional constraints might explain the high similarities among the genes. To test for gene conversion, we sequenced introns 2, 3, and 8 of all three Class I genes (total>15.0 kb) for five non-human primates--four great apes and one Old World Monkey (OWM)--and compared them with those of humans. The phylogenetic analysis shows each intron sequence clusters strongly within each gene, giving no evidence for gene conversion(s). Several lines of evidence indicate that the first split was between ADH1C and the gene that gave rise to ADH1A and ADH1B. We also analyzed cDNA sequences of the three genes that have been previously reported in mouse and Catarrhines (OWMs, chimpanzee, and humans) and found that the synonymous and non-synonymous substitution (dN/dS) ratios in all pairs are less than 1 representing purifying selection. This suggests that purifying selection is more important than gene conversion(s) in maintaining the overall sequence similarity among the Class I genes. We speculate that the highly conserved sequences on the three duplicated genes in primates have been achieved essentially by maintaining stability of the hetero-dimer formation that might have been related to dietary adaptation in primate evolution.

Alcohol Dehydrogenase↗

Nonhuman primate placental MHC expression: a model for exploring mechanisms of human maternal-fetal immune tolerance.

Placental contributions to the establishment of maternal-fetal immune tolerance, and placental influences on maturation and vascular development of the endometrium in the human have been difficult to explore directly. Although significant differences exist in organization and relevant gene expression between human and nonprimate placentas, the nonhuman primate has substantial potential to provide insights into the physiology of human pregnancy and maternal-fetal immune tolerance. In this report, we will summarize major histocompatability complex class I gene expression in the nonhuman primate placenta and present progress in characterizing the immune cells resident in the primate endometrium. Finally, we will outline new experimental approaches for modifying placental function now available to move research forward in this field.

Animals↗