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Evidence on primate phylogeny from epsilon-globin gene sequences and flanking regions.

Phylogenetic relationships among various primate groups were examined based on sequences of epsilon-globin genes. epsilon-globin genes were sequenced from five species of strepsirhine primates. These sequences were aligned and compared with other known primate epsilon-globin sequences, including data from two additional strepsirhine species, one species of tarsier, 19 species of New World monkeys (representing all extant genera), and five species of catarrhines. In addition, a 2-kb segment upstream of the epsilon-globin gene was sequenced in two of the five strepsirhines examined. This upstream sequence was aligned with five other species of primates for which data are available in this segment. Domestic rabbit and goat were used as outgroups. This analysis supports the monophyly of order Primates but does not support the traditional prosimian grouping of tarsiers, lorisoids, and lemuroids; rather it supports the sister grouping of tarsiers and anthropoids into Haplorhini and the sister grouping of lorisoids and lemuroids into Strepsirhini. The mouse lemur (Microcebus murinus) and dwarf lemur (Cheirogaleus medius) appear to be most closely related to each other, forming a clade with the lemuroids, and are probably not closely related to the lorisoids, as suggested by some morphological studies. Analysis of the epsilon-globin data supports the hypothesis that the aye-aye (Daubentonia madagascariensis) shares a sister-group relationship with other Malagasy strepsirhines (all being classified as lemuroids). Relationships among ceboids agree with findings from a previous epsilon-globin study in which fewer outgroup taxa were employed. Rates of molecular evolution were higher in lorisoids than in lemuroids.

Animals↗

Primate evolution at the DNA level and a classification of hominoids.

The genetic distances among primate lineages estimated from orthologous noncoding nucleotide sequences of beta-type globin loci and their flanking and intergenic DNA agree closely with the distances (delta T50H values) estimated by cross hybridization of total genomic single-copy DNAs. These DNA distances and the maximum parsimony tree constructed for the nucleotide sequence orthologues depict a branching pattern of primate lineages that is essentially congruent with the picture from phylogenetic analyses of morphological characters. The molecular evidence, however, resolves ambiguities in the morphological picture and provides an objective view of the cladistic position of humans among the primates. The molecular data group humans with chimpanzees in subtribe Hominina, with gorillas in tribe Hominini, orangutans in subfamily Homininae, gibbons in family Hominidae, Old World monkeys in infraorder Catarrhini, New World monkeys in semisuborder Anthropoidea, tarsiers in suborder Haplorhini, and strepsirhines (lemuriforms and lorisiforms) in order Primates. A seeming incongruency between organismal and molecular levels of evolution, namely that morphological evolution appears to have speeded up in higher primates, especially in the lineage to humans, while molecular evolution has slowed down, may have the trivial explanation that relatively small genetic changes may sometimes result in marked phenotypic changes.

Animals↗

Mitochondrial DNA evolution in primates: transition rate has been extremely low in the lemur.

Based on mitochondrial DNA (mt-DNA) sequence data from a wide range of primate species, branching order in the evolution of primates was inferred by the maximum likelihood method of Felsenstein without assuming rate constancy among lineages. Bootstrap probabilities for the maximum likelihood tree topology among alternatives were estimated without performing a maximum likelihood estimation for each resampled data set. Variation in the evolutionary rate among lineages was examined for the maximum likelihood tree by a method developed by Kishino and Hasegawa. From these analyses it appears that the transition rate of mtDNA evolution in the lemur has been extremely low, only about 1/10 that in other primate lines, whereas the transversion rate does not differ significantly from that of other primates. Furthermore, the transition rate in catarrhines, except the gibbon, is higher than those in the tarsier and in platyrrhines, and the transition rate in the gibbon is lower than those in other catarrhines. Branching dates in primate evolution were estimated by a molecular clock analysis of mtDNA, taking into account the rate of variation among different lines, and the results were compared with those estimated from nuclear DNA. Under the most likely model, where the evolutionary rate of mtDNA has been uniform within a great apes/human clade, human/chimpanzee clustering is preferred to the alternative branching orders among human, chimpanzee, and gorilla.

Animals↗

Accelerated evolution of cytochrome b in simian primates: adaptive evolution in concert with other mitochondrial proteins?

We have sequenced the cytochrome b gene of Horsfield's tarsier, Tarsius bancanus, to complete a data set of sequences for this gene from representatives of each primate infraorder. These primate cytochrome b sequences were combined with those from representatives of three other mammalian orders (cat, whale, and rat) in an analysis of relative evolutionary rates. The nonsynonymous nucleotide substitution rate of the cytochrome b gene has increased approximately twofold along lineages leading to simian primates compared to that of the tarsier and other primate and nonprimate mammalian species. However, the rate of transversional substitutions at fourfold degenerate sites has remained uniform among all lineages. This increase in the evolutionary rate of cytochrome b is similar in character and magnitude to that described previously for the cytochrome c oxidase subunit II gene. We propose that the evolutionary rate increase observed for cytochrome b and cytochrome c oxidase subunit II may underlie an episode of coadaptive evolution of these two proteins in the mitochondria of simian primates.

Adaptation, Physiological↗

Human disease-associated mitochondrial mutations fixed in nonhuman primates.

A number of human disease-associated sequences have been reported in other species, such as rodents, but compensatory changes appear to prevent these deleterious mutations from being expressed. The aim of this work was to compare the mitochondrial DNA of multiple primates to ascertain whether mitochondrial disease-causing sequences in humans are fixed in nonhuman primates. Indeed, 46 sequences related to human pathology were identified in 1 or more of the 12 studied nonhuman primates, the majority of which were associated with late-onset diseases. Most of these sequences can be explained by the presence of secondary compensatory changes that render these mutations phenotypically inert. Nonetheless, and since humans not only are the longest-lived primate but feature the largest brain, one hypothesis is that a gradual optimization of the human mitochondrion occurred in the hominid lineage driven by the need to optimize the aerobic energy metabolism to delay neurodegeneration. Therefore, it is also proposed that some of these disease-associated sequences in nonhuman primates may be linked to the evolution of human longevity and intelligence, indicating a general pattern of selection on longevity in the course of evolution of the human mitochondrion.

Animals↗

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↗

Levels of serum brain-derived neurotrophic factor in primates.

Brain-derived neurotrophic factor (BDNF) has been reported to exist not only in nervous tissue but also in serum. In contrast to the wealth of knowledge regarding the various physiological functions of BDNF in the nervous system, information about possible roles in other systems is limited. To elucidate the physiological function of serum BDNF in primates, it is first necessary to establish a method to determine the levels of BDNF in serum of primates. In the present study, we established an enzyme-linked immunosorbent assay (ELISA) method which we used to measure levels of serum BDNF in non-human primates. We found that serum BDNF levels were similar among several species of primates. The present results suggest that our BDNF ELISA may be useful in measuring serum BDNF concentration as a physiological marker, and that levels of serum BDNF may be similar among primates including humans.

Animals↗

Growth and allometry in primate masticatory muscles.

A study of the dry weight of primate and non-primate masticatory musculature permitted possible allometric and ontogenetic influences on this musculature to be explored. Using weight as an indicator of adult body size, all of the masticatory muscles examined (anterior temporalis, posterior temporalis, masseter, medial pterygoid, lateral pterygoid, digastrics, and total adductor mass) are isometric. This is true even when prosimians and non-primates are removed from consideration, leaving only adult anthropoid primates. Thus, size-related changes do not affect the masticatory musculature of anthropoids differently from the musculature of examined prosimians and non-primates. However, other measures of body size (skull length, head and body length) reveal a different picture. Yet, irrespective of the indicator of body size chosen, the allometric properties of the masticatory muscles appear similar and the fluctuations of the various muscle indices therefore reflect functional changes, and are not caused by allometry. Exudate-eating and frugivory are discussed in relation to body size and the development of the mandibular depressor muscles. The logs of the masticatory muscles do not show a significant correlation with age, except when species are followed across age grades. For the five anthropoid species for which this is possible, the medial and lateral pterygoid and digastric muscles are still not correlated with age. When all examined species are considered, some muscle ratios correlate significantly with age. Following anthropoid species across age grades singles out an early surge in growth of the medial pterygoid muscle over the masseter muscle, a situation which was apparent also in the general age correlation.

Age Factors↗

Evolutionary implications of primate endogenous retroviruses.

Endogenous DNA sequences related to retroviruses are probably present in all primates. By using approaches based on the polymerase chain reaction, two separate studies have revealed the evolutionary history of some of these sequences. In the first study, a retrovirus-like reverse transcriptase (RT) sequence homologous to that of Baboon endogenous virus (BaEV) has been identified in both Old World monkeys and African apes, but not in humans or Asian apes. This RT sequence is highly conserved at the amino acid level, but not the nucleotide level, in the baboon, African green monkey, Java macaque, chimpanzee, and gorilla. The patterns of nucleotide substitution indicate functional conservation and suggest that this RT sequence was present in the primate germline before apes and Old World monkeys diverged about 30 million years ago. In the second study, a comparison of endogenous proviral DNAs and their adjacent sequences has been used to analyze the evolutionary history of three previously reported human endogenous retroviruses, HERV-E(4.14), HERV-R(3), and HERV-Ia. It is shown that these retroviruses have also been resident in the primate line since before the ape-Old World monkey divergence. The implications of the presence of functionally conserved RT genes in the germlines of primates, and the potential for using integration sites as tools for analyzing phylogenetic relationships among primates and their retroviruses, are discussed.

Amino Acid Sequence↗

Nonhuman primate models for human disease.

The value of nonhuman primates as models for a variety of human diseases is well documented. These species have been used extensively during the past 25 years or so as models for a variety of bacterial, viral, and parasitic diseases, either as naturally occurring or experimentally induced infections. They are often the only nonhuman species susceptible to experimental infection with agents of human disease. Spontaneous diseases of nonhuman primates are often comparable to human diseases, and with the continued long-term maintenance of nonhuman primates in the laboratory as well as in domestic breeding colonies, it is reasonable to assume that additional disease models will be discovered. Such models may include degenerative diseases, diseases and/or lesions associated with the aging process, and genetic diseases. In this article we have reviewed four spontaneous diseases and one induced disease that have essentially identical counterparts in humans. Three of these are bacterial diseases that currently cause severe and sometimes fatal infections in humans; one is a degenerative disease that is usually progressive and fatal in humans, and one is possibly a genetic disease for which there is currently no animal model. The clinical and pathologic similarities between these nonhuman primate diseases and their human counterpart make these nonhuman primate diseases potentially valuable models for further studies on the etiology, pathogenesis, and treatment of these serious and often fatal human diseases.

Amyloidosis↗

The primate Harderian gland: Does it really exist?

The Harderian gland, an anterior orbital structure, is either absent or vestigial in primates. This is based upon gross anatomical observations of scattered adult specimens. Though largely absent in the adult human, it is present in the fetal and neonatal stages. Thus, histological examination of the orbital region of neonatal material was undertaken in other primates. The orbital region of neonatal specimens of 12 species of strepsirrhines (Lemuriformes and Lorisiformes), and haplorhine (tarsiers and callitrichids) was examined. The Harderian gland is ensconced in either periorbital fat or connective tissue and thus was not readily identifiable gross anatomically. Thus, it may have been missed in the anatomical studies. Tarsal glands are present in all neonatal primate eyelids. The relative size of the neonatal primate Harderian gland can be subdivided into five separate categories, ranging from large to absent (tarsiers), with no apparent phylogenetic trends. Thus, the Harderian gland is present in numerous primates at birth, quite possibly all strepsirrhines. The positive findings on callitrichids question whether any anthropoids lack the Harderian gland postnatally. The enigmatic tarsier appears to possess another apomorphic trait in lacking a Harderian gland. Further study is required to determine the role of this gland and its relationship with the tarsal glands.

Animals↗

Trypanosoma cruzi transmission in a captive primate unit, Rio de Janeiro, Brazil.

A breeding in captivity program of neotropical primates for subsequent reintroduction in nature is in progress at the Primatology Center of Rio de Janeiro (CPRJ). Almost 200 animals of 20 species that include both wild captured animals and specimens born in captivity are maintained in CPRJ. Here, we examined 198 primates of CPRJ for infection with the protozoan parasite Trypanosoma cruzi. The animals included 18 species of eight genera. We also performed an "ad lib" search for triatomines that could be incriminated as putative transmitters of the protozoan in this scenario. Anti-T. cruzi antibodies were observed (by indirect immunofluorescence assay-IFA) in 40 monkeys (26.5%). Four Panstrongylus megistus were collected in the monkey's food storage room near the cages and in human dwellings in the proximity to CPRJ. T. cruzi were isolated from nine primates of two genera (Leontopithecus and Saguinus) and from two individuals of the vector P. megistus. The transmission inside the cages could be attested by the isolation of the T. cruzi from primates born in captivity. Multi-locus enzyme electrophoresis (MLEE) demonstrated that the two isolates from Saguinus bicolor bicolor displayed a zymodeme 1 profile in four out of five tested enzymes, while all isolates derived from Leontopithecus showed zymodeme 2 for four out of the five tested enzymes. Mini-exon gene analysis genotyped all isolates as T. cruzi II, which is associated with human disease in Brazil. A wild primate unit such as CPRJ, located inside the forest and near to human dwellings and with T. cruzi II infected animals, deserves a careful surveillance in order to prevent expansion of the infection.

Animals↗

Nonhuman primate embryonic stem cells as a preclinical model for hematopoietic and vascular repair.

Stem cell-based regenerative medicine therapies have been touted recently as a novel therapeutic approach to treat and cure a wide range of diseases. Both adult and embryonic stem (ES) cells can serve as important sources of precursor cells to derive more mature cells potentially utilized for clinical applications. Nonhuman primates have proven useful as a preclinical model, as demonstrated in studies of hematopoietic cell transplantation, gene therapy, and other areas. The derivation of nonhuman primate ES cells now provides an optimal resource to characterize and test ES cell-based therapies prior to trials with human ES cells. This review describes work to define strategies and mechanisms to derive blood and endothelial cells from nonhuman primate ES cells isolated from various species. Preclinical testing that solely relies on studies of putative therapeutic cells derived from mouse ES cells transplanted into other mice, or analyses of human ES cell-derived cells transplanted into immunodeficient or immunosuppressed rodents may not be predictive of efficacy in subsequent human trials. However, future testing using nonhuman primate ES cell-derived therapeutic cells done as an allogeneic transplant may best predict success for subsequent studies using human ES cells. Therefore, additional research on nonhuman primate ES cells, in addition to work on mouse and human ES cells, is greatly needed to facilitate clinical translation of new stem cell treatments.

Animals↗

Protective correlates against HIVs may have evolved in human populations in the areas of historic occurrence of primate-to-man transmissions of SIVs ancestral to HIVs: studies in these populations may provide crucial insights for treatment and prevention of HIV infection.

Recent findings suggest that Human Immunodeficiency Viruses, HIV-1 and 2, might have been transmitted to humans from particular primate species. It is thought that some Simian Immunodeficiency Viruses (SIVs), from which HIVs presumably originated, existed in their primate hosts for ages. Behavioral characteristics increasing the probability of contact between these primates and humans (such as keeping monkeys for pets, hunting monkeys for food, improper handling of the monkey meat, etc.) documented in some African countries could have facilitated cross-species transmissions (CSTs) of HIVs. As it has been shown, multiple CSTs took place for both HIVs (1 and 2) and then, in a globalizing world, these local events led to the pandemic. Here, it is brought forward that in the regions of epizooty of SIVs closely related to HIVs, some human populations might have had exposure history to these viruses dating back hundreds years. Lacking the important framework for further spread provided by nowadays globalization, these CSTs could have led to isolated local HIV outbreaks limited to particular tribes or groups. The infections could have extinguished some populations while on the other hand provided evolutionary pressure to select for mechanisms protective for HIV infection and/or disease. Thus, here it is hypothesized that in the areas of the habitat of primates infected with SIVs, from which HIVs are thought to be originated, there could be historically exposed populations which might possess biological correlates of protection from HIVs. Current knowledge on the distribution of primates hosting HIV-related SIVs suggests that epidemiological, primatological, anthropological and molecular biological studies in the areas of Cameroon, Gabon, both Congos and Equatorial Guinea (for HIV-1) and Guinea-Bissau, Senegal, Guinea, Ivory Cost, Sierra Leone and Liberia (for HIV-2) could lead to the discoveries of correlates of protection against HIVs. It is also hypothesized that virology studies in the same areas might reveal less virulent and/or infective viruses which could provide insights in the HIV pathogenesis and vaccinology.

Acquired Immunodeficiency Syndrome↗

Characterization of primate trypanosome lytic factors.

Humans are one of the few species that resist infection by Trypanosoma brucei brucei because the parasites are killed by lytic factors found in human serum. Trypanosome lytic factors (TLFs) are protein/lipid complexes that contain apolipoprotein A-I (apoA-I), and are therefore a class of high density lipoproteins (HDLs). Haptoglobin-related protein (Hpr) is a unique protein component of TLFs, and its expression has only been demonstrated in humans. Trypanolytic activity has only been found in the sera of five primates: humans, gorillas, mandrills, baboons and sooty mangabeys. We describe here previously unidentified components of highly purified human TLF1: apolipoprotein L-I (apoL-I), human cathelicidin antimicrobial peptide 18 (hCAP18) and glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). However, we found that hCAP18 and GPI-PLD, along with apoA-I, are common components of both lytic and non-lytic primate HDLs. In contrast, Hpr, which has been previously implicated as the main lytic component of TLF1, was a unique component of all trypanolytic primate HDLs. Furthermore, a polyclonal antiserum to Hpr neutralized the lytic activity from humans and baboons. ApoL-I, a candidate lytic component of human serum, was not immunologically or genetically detectable in two primate species with lytic activity. Polyclonal antiserum to apoL-I also did not neutralize TLF activity in a total human HDL preparation. These findings suggest that apoL-I is not essential in all primate TLFs, and apoL-I alone is not sufficient for optimal trypanosome lytic activity in human TLF.

Amino Acid Sequence↗

Are subordinates always stressed? A comparative analysis of rank differences in cortisol levels among primates.

Among primate species there is pronounced variation in the relationship between social status and measures of stress physiology. An informal meta-analysis was designed to investigate the basis of this diversity across different primate societies. Species were included only if a substantial amount of published information was available regarding both social behavior and rank-related differences in stress physiology. Four Old World and three New World species met these criteria, including societies varying from small-group, singular cooperative breeders (common marmoset and cotton top tamarin) to large-troop, multi-male, multi-female polygynous mating systems (rhesus, cynomolgus, talapoin, squirrel monkeys, and olive baboon). A questionnaire was formulated to obtain information necessary to characterize the stress milieu for individuals in particular primate societies. We standardized cortisol values within each species by calculating the ratio of basal cortisol concentrations of subordinates to those of dominants in stable dominance hierarchies and expressing the ratio as a percentage (relative cortisol levels). The meta-analysis identified two variables that significantly predicted relative cortisol levels: subordinates exhibited higher relative cortisol levels when they (1). were subjected to higher rates of stressors, and (2). experienced decreased opportunities for social (including close kin) support. These findings have important implications for understanding the different physiological consequences of dominant and subordinate social status across primate societies and how social rank may differ in its behavioral and physiological manifestations among primate societies.

Aggression↗

Use of keyed character string data structures and operators in models of primate groups.

Many primate populations exhibit forms of organization that are both complex and highly dynamic. A prototype of a general purpose primate population computer modelling system has been developed; this modelling system provides data structures and operators that facilitate computer representation of many static and dynamic features of primate population organization. In this system, primate group structures are represented by text strings known as key strings. A key string begins with a label or key character that identifies its population element type. The label character is followed by data fields contained between bounds marker characters. Nested key strings can be used to concisely represent many of the structural features of social groups in different primate species. Changes in group structures are accomplished by key string insertion, deletion and move operations. Models of structures and processes in island, rhesus monkey and hamadryas baboon populations built with this prototype modelling system are discussed. In these pilot applications, use of key string data structures and operators greatly simplifies many aspects of model construction.

Animals↗

Screening for simian foamy virus infection by using a combined antigen Western blot assay: evidence for a wide distribution among Old World primates and identification of four new divergent viruses.

Simian foamy viruses (SFVs) belong to a genetically and antigenically diverse class of retroviruses that naturally infect a wide range of nonhuman primates (NHPs) and can also be transmitted to humans occupationally exposed to NHPs. Current serologic detection of SFV infection requires separate Western blot (WB) testing by using two different SFV antigens [SFV(AGM) (African green monkey) and SFV(CPZ) (chimpanzee)]. However, this method is labor intensive and validation is limited to only small numbers of NHPs. To facilitate serologic SFV testing, we developed a WB assay that combines antigens from both SFV(AGM) and SFV(CPZ). The combined-antigen WB (CA-WB) assay was validated with 145 serum samples from 129 NHPs (32 African and Asian species) and 16 humans, all with known SFV infection status determined by PCR. Concordant CA-WB results were obtained for all 145 PCR-positive or -negative primate and human specimens, giving the assay a 100% sensitivity and specificity. In addition, no reactivity was observed in sera from persons positive for human immunodeficiency virus or human T cell lymphotropic virus (HIV/HTLV) (n = 25) or HIV/HTLV-negative U.S. blood donors (n = 100). Using the CA-WB assay, we screened 360 sera from 43 Old World primate species and found an SFV prevalence of about 68% in both African and Asian primates. We also isolated SFV from the blood of four seropositive primates (Allenopithecus nigroviridis, Trachypithecus françoisi, Hylobates pileatus, and H. leucogenys) not previously known to be infected with SFV. Phylogenetic analysis of integrase sequences from these isolates confirmed that all four SFVs represent new, distinct, and highly divergent lineages. These results demonstrate the ability of the CA-WB assay to detect infection in a large number of NHP species, including previously uncharacterized infections with divergent SFVs.

Africa↗