A missing piece of the Papio puzzle: Gorongosa baboon phenostructure and intrageneric relationships.

Most authors recognize six baboon species: hamadryas (Papio hamadryas), Guinea (Papio papio), olive (Papio anubis), yellow (Papio cynocephalus), chacma (Papio ursinus), and Kinda (Papio kindae). However, there is still debate regarding the taxonomic status, phylogenetic relationships, and the amount of gene flow occurring between species. Here, we present ongoing research on baboon morphological diversity in Gorongosa National Park (GNP), located in central Mozambique, south of the Zambezi River, at the southern end of the East African Rift System. The park exhibits outstanding ecological diversity and hosts more than 200 baboon troops. Gorongosa National Park baboons have previously been classified as chacma baboons (P. ursinus). In accordance with this, two mtDNA samples from the park have been placed in the same mtDNA clade as the northern chacma baboons. However, GNP baboons exhibit morphological features common in yellow baboons (e.g., yellow fur color), suggesting that parapatric gene flow between chacma and yellow baboons might have occurred in the past or could be ongoing. We investigated the phenostructure of the Gorongosa baboons using two approaches: 1) description of external phenotypic features, such as coloration and body size, and 2) 3D geometric morphometric analysis of 43 craniofacial landmarks on 11 specimens from Gorongosa compared to a pan-African sample of 352 baboons. The results show that Gorongosa baboons exhibit a mosaic of features shared with southern P. cynocephalus and P. ursinus griseipes. The GNP baboon phenotype fits within a geographic clinal pattern of replacing allotaxa. We put forward the hypothesis of either past and/or ongoing hybridization between the gray-footed chacma and southern yellow baboons in Gorongosa or an isolation-by-distance scenario in which the GNP baboons are geographically and morphologically intermediate. These two scenarios are not mutually exclusive. We highlight the potential of baboons as a useful model to understand speciation and hybridization in early human evolution.

Molecular suitability of the chacma baboon in human-targeted Von Willebrand factor directed studies.

BACKGROUND: Von Willebrand factor (VWF) has a central role in primary haemostasis and is a popular pharmaceutical target in the prevention and treatment of disorders such as acute coronary syndrome and thrombotic thrombocytopenic purpura. We have evaluated numerous possible treatments targeting VWF in the chacma baboon. Unfortunately, no data exist regarding the molecular similarity of the chacma baboon and human VWF protein, resulting in limited translatability of results. METHODS: Sanger sequencing was performed of the functionally vital VWF exon 28. The sequences were then compared to the human reference sequence. RESULTS: The baboon and human VWF amino acid sequences were 99.1% similar, with only 4 radical amino acid changes found. No radical amino acid changes were found within the functionally vital areas of the amino acid sequence. CONCLUSION: The chacma baboon VWF is similar enough to the human to produce reliable and translatable pre-clinical results with human-targeted anti-VWF agents.

Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp.) supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef) through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

Kinda baboons (Papio kindae) and grayfoot chacma baboons (P. ursinus griseipes) hybridize in the Kafue river valley, Zambia.

The ranges of small kinda (Papio kindae) and much larger grayfooted chacma (P. ursinus griseipes) baboons adjoin in the Kafue National Park, Zambia. In a visual survey of baboons at 48 sites in the Kafue River drainage we found that, contrary to previous reports, groups at the species interface near the town of Ngoma are phenotypically diverse and presumably formed by multigenerational hybridization. Mitochondrial and/or Y-chromosome genetic markers from fecal samples (N=164) collected at 29 sites support this conclusion. Groups with phenotypic signs of a history of hybridization also had taxon-specific mitochondria and Y-haplotypes from both parental species. Although the distribution of mitochondrial haplotypes largely mirrored that of external phenotypes, a significant proportion of male specimens from grayfoot as well as hybrid groups carried kinda Y-chromosomes, and kinda Y-chromosomes were involved in all observed cases of mitochondrial/Y-chromosome discordance. These observations are consistent with, though they do not prove, a population history in which the range of chacmas and the hybrid zone have advanced at the expense of the kinda range. They also suggest that, unexpectedly, kinda male×chacma female matings are much more common than the reciprocal cross in the ancestry of hybrids. We suggest that distinctive male kinda behavior and the "juvenile" appearance of kinda baboons of both sexes, perhaps combined with obstetric difficulties of a small kinda female carrying the large offspring of a chacma male, may account for this bias.

Induction of bone formation by transforming growth factor-beta2 in the non-human primate Papio ursinus and its modulation by skeletal muscle responding stem cells.

OBJECTIVES: Four adult non-human primates Papio ursinus were used to study induction of bone formation by recombinant human transforming growth factor-beta(2) (hTGF-beta(2)) together with muscle-derived stem cells. MATERIALS AND METHODS: The hTGF-beta(2) was implanted in rectus abdominis muscles and in calvarial defects with and without addition of morcellized fragments of striated muscle, harvested from the rectus abdominis or temporalis muscles. Expression of osteogenic markers including osteogenic protein-1, bone morphogenetic protein-3 and type IV collagen mRNAs from generated specimens was examined by Northern blot analysis. RESULTS: Heterotopic intramuscular implantation of 5 and 25 microg hTGF-beta(2) combined with 100 mg of insoluble collagenous bone matrix yielded large corticalized mineralized ossicles by day 30 with remodelling and induction of haematopoietic marrow by day 90. Addition of morcellized rectus abdominis muscle to calvarial implants enhanced induction of bone formation significantly by day 90. CONCLUSIONS: In Papio ursinus, in marked contrast to rodents and lagomorphs, hTGF-beta(2) induced large corticalized and vascularized ossicles by day 30 after implantation into the rectus abdominis muscle. This striated muscle contains responding stem cells that enhance the bone induction cascade of hTGF-beta(2). Induction of bone formation by hTGF-beta(2) in the non-human primate Papio ursinus may occur as a result of expression of bone morphogenetic proteins on heterotopic implantation of hTGF-beta(2); the bone induction cascade initiated by mammalian TGF-beta proteins in Papio ursinus needs to be re-evaluated for novel molecular therapeutics for induction of bone formation in clinical contexts.

A female signal reflects MHC genotype in a social primate.

BACKGROUND: Males from many species are believed to advertise their genetic quality through striking ornaments that attract mates. Yet the connections between signal expression, body condition and the genes associated with individual quality are rarely elucidated. This is particularly problematic for the signals of females in species with conventional sex roles, whose evolutionary significance has received little attention and is poorly understood. Here we explore these questions in the sexual swellings of female primates, which are among the most conspicuous of mammalian sexual signals and highly variable in size, shape and colour. We investigated the relationships between two components of sexual swellings (size and shape), body condition, and genes of the Major Histocompatibility Complex (MHC) in a wild baboon population (Papio ursinus) where males prefer large swellings. RESULTS: Although there was no effect of MHC diversity on the sexual swelling components, one specific MHC supertype (S1) was associated with poor body condition together with swellings of small size and a particular shape. The variation in swelling characteristics linked with the possession of supertype S1 appeared to be partially mediated by body condition and remained detectable when taking into account the possession of other supertypes. CONCLUSIONS: These findings suggest a pathway from immunity genes to sexual signals via physical condition for the first time in females. They further indicate that mechanisms of sexual selection traditionally assigned to males can also operate in females.

Estimation of parameters of inbreeding and genetic drift in populations with overlapping generations.

Many long-lived plant and animal species have nondiscrete overlapping generations. Although numerous models have been developed to predict the effective sizes (N(e)) of populations with overlapping generations, they are extremely difficult to apply to natural populations because of the large array of unknown and elusive life-table parameters involved. Unfortunately, little work has been done to estimate the N(e) of populations with overlapping generations from marker data, in sharp contrast to the situation of populations with discrete generations for which quite a few estimators are available. In this study, we propose an estimator (EPA, estimator by parentage assignments) of the current N(e) of populations with overlapping generations, using the sex, age, and multilocus genotype information of a single sample of individuals taken at random from the population. Simulations show that EPA provides unbiased and accurate estimates of N(e) under realistic sampling and genotyping effort. Additionally, it yields estimates of other interesting parameters such as generation interval, the variances and covariances of lifetime family size, effective number of breeders of each age class, and life-table variables. Data from wild populations of baboons and hihi (stitchbird) were analyzed by EPA to demonstrate the use of the estimator in practical sampling and genotyping situations.

Mitochondrial DNA analysis reveals Plio-Pleistocene diversification within the chacma baboon.

Modern baboons evolved as a distinct lineage prior to 2.5 Mya. Previous scenarios of diversification within this lineage have assessed the phylogenetic position of the chacma baboon of southern Africa relative to other baboons, but have not examined variation within this taxon. Here we provide a phylogenetic analysis of lineage diversity across the range of the chacma baboon, and show that: (1) chacma baboons diverged as a separate lineage at approximately 1.84 Mya; (2) the chacma lineage is characterised by a deep lineage split dividing chacmas into northeastern (1.52 Mya) and southwestern (1.22 Mya) clades; (3) ruacana baboons of Namibia form their own distinct monophyletic group within the southwestern clade, emerging approximately 0.68 Mya. These patterns likely result from a complex interplay of genetic drift and gene flow as the chacma lineage diversified across a broad geographic landscape during the climatically variable Plio-Pleistocene.

Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock.

Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock. Measurement of AVP levels has limitations due to its short half-life and cumbersome detection method. Copeptin is a more stable peptide derived from the same precursor molecule. We evaluated the plasma copeptin concentration in two independent studies: first, in an experimental baboon model of hemorrhagic shock, and second, in a prospective observational study of 101 consecutive critically ill patients at a university hospital. Copeptin was measured with a newly developed sandwich immunoassay using two polyclonal antibodies to the C-terminal region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269 pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin values increased significantly with the severity of the disease and were in patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]), in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504 pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs. controls <0.001). On admission, circulating copeptin levels were higher in nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5-386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r = 0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression model including other covariates besides copeptin (e.g., determinants of fluid status) on survival, serum copeptin levels were the only independent significant predictor of outcome (P = 0.03). Copeptin concentrations are elevated in hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as compared with survivors, suggesting copeptin as a prognostic marker in sepsis. The availability of a reliable assay for the measurement of AVP release can also prove useful for the assessment of fluid and osmosis status in various diseases.

Molecular study of Mhc-DRB in wild chacma baboons reveals high variability and evidence for trans-species inheritance.

The MHC class II genes of many primate species were investigated extensively in recent years. However, while Mhc-DRB genes were studied in Old World monkeys such as rhesus macaques, the Mhc-DRB of baboons was only studied in a limited way. Because of their close anatomical and physiological relationship to humans, baboons are often used as models for reproduction and transplantation research. Baboons are also studied as a model species in behavioural ecology. Thus, identification of MHC genes would provide a foundation for studies of Mhc, biology and behaviour. Here, we describe the use of PCR, cloning, denaturing gradient gel electrophoresis (DGGE) and sequencing to identify Mhc-DRB sequences in wild chacma baboons (Papio ursinus). We amplified the highly variable second exon of baboon Mhc-DRB sequences using generic DRB primers. To validate and optimize the DGGE protocol, four DNA samples were initially studied using cloning and sequencing. Clones were screened using a novel RFLP approach to increase the number of clones identified for each individual. Results from cloning and sequencing were used to optimise DGGE conditions for Mhc-DRB genotyping of the remaining study subjects. Using these techniques, we identified 16 Paur-DRB sequences from 30 chacma baboons. On the basis of phylogenetic tree analyses, representatives of the Mhc-DRB1 and Mhc-DRB5 loci, and 13 different DRB lineages were identified. Evidence for trans-species inheritance of some Mhc-DRB sequences comes from high identity between the new Paur-DRB sequences and sequences from Papio cynocephalus, Macaca mulatta and possibly Galago moholi.

Correlation between gene expression and morphological alterations in baboon carotid after balloon dilatation injury.

Treatment for fibroproliferative restenosis after angioplasty and endovascular surgery is an unmet medical need. Rational therapy and drug design still lack the very basic knowledge about the underlying biological processes leading to pathological changes in the vessel wall. We have developed a primate model for vascular response to denudation-overstretch injury of baboon carotid artery. With this model, we have investigated the time course of vascular expression of 41,000 human cDNA clones and correlated these changes with carotid histology and function. Analysis revealed 20,788 differentially regulated cDNA clones. After high stringency data selection, the most prominently regulated 1629 cDNA clones representing 1510 genes of known function were clustered. Genes corresponding to functional and anatomical alterations in the injured carotid wall were further aligned into functional groups according to Gene Ontology classification. The observed expression patterns faithfully reflected the functional and anatomical alterations observed in the vascular wall in response to injury. The analysis presents a tentative model for genomic response to balloon catheter injury and a road map to identify time-related genomic alterations in human vascular specimens.