Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation.

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation.

The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct.

BACKGROUND: Treponema pallidum subsp. pertenue (TPE) is the causative agent of human yaws. Yaws is currently reported in 13 endemic countries in Africa, southern Asia, and the Pacific region. During the mid-20th century, a first yaws eradication effort resulted in a global 95% drop in yaws prevalence. The lack of continued surveillance has led to the resurgence of yaws. The disease was believed to have no animal reservoirs, which supported the development of a currently ongoing second yaws eradication campaign. Concomitantly, genetic evidence started to show that TPE strains naturally infect nonhuman primates (NHPs) in sub-Saharan Africa. In our current study we tested hypothesis that NHP- and human-infecting TPE strains differ in the previously unknown parts of the genomes. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we determined complete (finished) genomes of ten TPE isolates that originated from NHPs and compared them to TPE whole-genome sequences from human yaws patients. We performed an in-depth analysis of TPE genomes to determine if any consistent genomic differences are present between TPE genomes of human and NHP origin. We were able to resolve previously undetermined TPE chromosomal regions (sequencing gaps) that prevented us from making a conclusion regarding the sequence identity of TPE genomes from NHPs and humans. The comparison among finished genome sequences revealed no consistent differences between human and NHP TPE genomes. CONCLUSION/SIGNIFICANCE: Our data show that NHPs are infected with strains that are not only similar to the strains infecting humans but are genomically indistinguishable from them. Although interspecies transmission in NHPs is a rare event and evidence for current spillover events is missing, the existence of the yaws bacterium in NHPs is demonstrated. While the low risk of spillover supports the current yaws treatment campaign, it is of importance to continue yaws surveillance in areas where NHPs are naturally infected with TPE even if yaws is successfully eliminated in humans.

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons.

Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.

A global catalog of whole-genome diversity from 233 primate species.

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.

Genome-wide coancestry reveals details of ancient and recent male-driven reticulation in baboons.

Baboons (genus Papio ) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high coverage whole genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and inter-species gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal novel patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes. One-Sentence Summary: Genomic data for 225 baboons reveal novel sites of inter-species gene flow and local effects due to differences in admixture.

Investigation of the origin of scatter components transmitted through anti-scatter grids in X-ray Digital Imaging system using Monte Carlo Simulation.

Background: Projection diagnostic X-ray images are inherently affected by the masking effects of transmitted scatter. Spatially distributed transmitted scatter degrades image quality engendering need for effective scatter correction protocol. Objectives: To investigate origin of scatter components transmitted through anti-scatter grids to the detector of digital radiography system using Monte Carlo simulation. Methods: Over 107 photons were exposed through the reconstructed MC simulation phantom. Transmitted photons (primary and scatter) were scored as fluence, dose and deposited energy. Scatter components were investigated analytically over varying phantom thickness, tube kV and grid characteristics. Test disks were exposed as ROI embedded in phantom to evaluate the potential contrast improvement in image quality with the proposed technique. Results: Simulated and experimental results were comparable and in agreement with literature. SPR and SF mean values of 10.5, 0.314 and 7.96, 0.242 through grids of ratio 10:1 and 16:1 respectively was observed. Analysis of scatter components generation in object, grid's assembly, and fluorescent yields gave mean values of 0.815, 0.167 and 0.017, respectively. Image contrast was observed to increase with tube voltage and grid ratio. Conclusion: Achieving better image contrast, reduced patient dose and low scatter transmission while maintaining superior image quality, using grids with high grid ratio and selectivity is recommended.

Mathematical modelling Treponema infection in free-ranging Olive baboons (Papio anubis) in Tanzania.

Yaws is a chronic infection caused by the bacterium Treponema pallidum susp. pertenue (TPE) that was thought to be an exclusive human pathogen but was recently found and confirmed in nonhuman primates. In this paper, we develop the first compartmental ODE model for TPE infection with treatment of wild olive baboons. We solve for disease-free and endemic equilibria and give conditions on local and global stability of the disease-free equilibrium. We calibrate the model based on the data from Lake Manyara National Park in Tanzania. We use the model to help the park managers devise an effective strategy for treatment. We show that an increasing treatment rate yields a decrease in disease prevalence. This indicates that TPE can be eliminated through intense management in closed population. Specifically, we show that if the whole population is treated at least once every 5-6 years, a disease-free equilibrium can be reached. Furthermore, we demonstrate that to see a substantial decrease of TPE infection to near-elimination levels within 15 years, the whole population needs to be treated every 2-3 years.

Mito-phylogenetic relationship of the new subspecies of gentle monkey Cercopithecus mitis manyaraensis, Butynski & De Jong, 2020.

In 2020, a new subspecies was described in the Cercopithecus mitis complex, the Manyara monkey C. m. manyaraensis, Butynski & De Jong, 2020. The internal taxonomy of this species complex is still debated, and the phylogenetic relationships among the taxa are unclear. Here we provide the first mitochondrial sequence data for C. m. manyaraensis to determine its position within the mitochondrial phylogeny of C. mitis. This subspecies clusters within the youngest (internal divergences between 1.01 and 0.42 Ma) of three main taxonomic clades of C. mitis. Its sister lineages are C. m. boutourlinii (Ethiopia), C. m. albotorquatus (Kenya and Somalia), C. m. albogularis (Kenya and Tanzania), and C. m. monoides (Tanzania and Mozambique). In general, the phylogenetic tree of C. mitis based on mitochondrial sequence data indicates several paraphyletic relationships within the C. mitis complex. As in other African cercopithecines (e.g. Papio and Chlorocebus), these data are suitable for reconstructing historic biogeographical patterns, but they are only of limited value for delimitating taxa.

Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas.

Primates have adapted to numerous environments and lifestyles but very few species are native to high elevations. Here we investigated high-altitude adaptations in the gelada (Theropithecus gelada), a monkey endemic to the Ethiopian Plateau. We examined genome-wide variation in conjunction with measurements of haematological and morphological traits. Our new gelada reference genome is highly intact and assembled at chromosome-length levels. Unexpectedly, we identified a chromosomal polymorphism in geladas that could potentially contribute to reproductive barriers between populations. Compared with baboons at low altitude, we found that high-altitude geladas exhibit significantly expanded chest circumferences, potentially allowing for greater lung surface area for increased oxygen diffusion. We identified gelada-specific amino acid substitutions in the alpha-chain subunit of adult haemoglobin but found that gelada haemoglobin does not exhibit markedly altered oxygenation properties compared with lowland primates. We also found that geladas at high altitude do not exhibit elevated blood haemoglobin concentrations, in contrast to the normal acclimatization response to hypoxia in lowland primates. The absence of altitude-related polycythaemia suggests that geladas are able to sustain adequate tissue-oxygen delivery despite environmental hypoxia. Finally, we identified numerous genes and genomic regions exhibiting accelerated rates of evolution, as well as gene families exhibiting expansions in the gelada lineage, potentially reflecting altitude-related selection. Our findings lend insight into putative mechanisms of high-altitude adaptation while suggesting promising avenues for functional hypoxia research.

Road-based line distance surveys overestimate densities of olive baboons.

Estimating population density and population dynamics is essential for understanding primate ecology and relies on robust methods. While distance sampling theory provides a robust framework for estimating animal abundance, implementing a constrained, non-systematic transect design could bias density estimates. Here, we assessed potential bias associated with line distance sampling surveys along roads based on a case study with olive baboons (Papio anubis) in Lake Manyara National Park (Tanzania). This was achieved by comparing density estimates of olive baboons derived from road transect surveys with density estimates derived from estimating the maximum number of social groups (via sleeping site counts) and multiplying this metric with the estimated average size of social groups. From 2011 to 2019, we counted olive baboons along road transects, estimated survey-specific densities in a distance sampling framework, and assessed temporal population trends. Based on the fitted half-normal detection function, the mean density was 132.5 baboons km-2 (95% CI: 110.4-159.2), however, detection models did not fit well due to heaping of sightings on and near the transects. Density estimates were associated with relatively wide confidence intervals that were mostly caused by encounter rate variance. Based on a generalized additive model, baboon densities were greater during the rainy seasons compared to the dry seasons but did not show marked annual trends. Compared to estimates derived from the alternative method (sleeping site survey), distance sampling along road transects overestimated the abundance of baboons more than threefold. Possibly, this overestimation was caused by the preferred use of roads by baboons. While being a frequently used technique (due to its relative ease of implementation compared to spatially randomized survey techniques), inferring population density of baboons (and possibly other species) based on road transects should be treated with caution. Beyond these methodological concerns and considering only the most conservative estimates, baboon densities in LMNP are among the highest across their geographic distribution range.

Female post-copulatory behavior in a group of olive baboons (Papio anubis) infected by Treponema pallidum.

Pathogens exert a profound and pervasive cost on various aspects of primate sociality and reproduction. In olive baboons (Papio anubis) at Lake Manyara National Park, Tanzania, genital skin ulcers, caused by the bacterium Treponema pallidum subsp. pertenue, are associated with increased female mating avoidance and altered male mating patterns at a pre-copulatory and copulatory level. Beyond this, mating is also comprised of post-copulatory interactions among sexual partners (i.e., copulation calls, darting [post-copulatory sprint away from the male], and post-copulatory grooming). In baboons, female post-copulatory behavior is hypothesized to incite male-male competition, promote subsequent copulations, and/or strengthen the bonds between the mating pairs. Due to a higher reproductive burden (i.e. pregnancy, lactation, infant rearing), females should avoid proceptive behavior after mating to decrease further exposure to potential pathogens. To investigate whether the presence of genital skin ulcers has an impact at the post-copulatory level, we analyzed 517 copulation events of 33 cycling females and 29 males with and without genital skin ulcers. The occurrence of female post-copulatory behaviors was not altered by genital skin ulcerations in males. Similar to other baboon populations, females in our study group were more likely to utter copulation calls after an ejaculatory copulation. The likelihood of darting was higher after ejaculatory copulations and with the presence of copulation calls. Post-copulatory grooming (i.e., occurring within 15 seconds after a copulation) was not frequently observed. Our results indicate that despite the presence of conspicuous signs of disease, female post-copulatory behavior was not affected by the genital health status of the males. This indicates that in our study group, infection cues caused by T. pallidum subsp. pertenue play a major role before and during mating, but not after mating. The post-copulatory behavior of females is most likely affected by physiological or evolutionary constraints other than sexually transmitted infections.

Cardiac tamponade: Better prognosis in association with pulmonary embolism: Case report.

The tamponade leads to an increase in intrapericardial pressure, which impairs the diastolic filling of the ventricles and reduces ejection. However, the association with pulmonary arterial hypertension, which in turn leads to an intracardiac hyper-pressure, constitutes a compensatory mechanism. We report the case of a 23 year old patient followed for anemia due to martial deficiency for 2 years, who consulted us with right heart failure evolving for 5 months, a hemoptoic cough and chest tightness. The entire workup revealed a pericardial and pleural tamponade of tuberculous origin associated with a pulmonary embolism evaluated at 15% according to the Qanadli score. After stabilization of her hemodynamic state, the patient was put on anti-bacillary and anticoagulant treatment with a good improvement of her cardiopulmonary state. She was discharged after 1 month (satisfactory check-up), regularly followed up in outpatient clinic with check-up of hemostasis and cardiac echography every 2 weeks. She was declared cured of her tuberculosis after 6 months of treatment. There was no recurrence after two years of follow-up. The combination of tamponade and pulmonary hypertension is synergistic in that it improves the patient's prognosis.

New mitogenomic lineages in Papio baboons and their phylogeographic implications.

OBJECTIVES: Incomplete and/or biased sampling either on a taxonomic or geographic level can lead to delusive phylogenetic and phylogeographic inferences. However, a complete taxonomic and geographical sampling is often and for various reasons impossible, particularly for widespread taxa such as baboons (Papio spp.). Previous studies on baboon phylogeography identified several sampling gaps, some of which we fill by investigating additional material including samples from museum specimens. MATERIALS AND METHODS: We generated 10 new mitochondrial genomes either via conventional PCR and subsequent Sanger sequencing from two blood samples or via high-throughput shotgun sequencing from degraded DNA extracted from eight museum specimens. Phylogenetic relationships and divergence times among baboon lineages were determined using maximum-likelihood and Bayesian inferences. RESULTS: We identified new mitochondrial lineages in baboons from Central Africa (Chad, the Central African Republic), from the Mahale, and the Udzungwa Mountains (Tanzania), with the latter likely representing a case of mitochondrial capture from sympatric kipunjis (Rungwecebus kipunji). We also found that the mitochondrial clades of olive baboons found in Ivory Coast and Tanzania extend into Niger and the Democratic Republic of Congo, respectively. Moreover, an olive baboon from Sierra Leone carries a mitochondrial haplotype usually found in Guinea baboons, suggesting gene flow between these two species. DISCUSSION: The extension of the geographic sampling by including samples from areas difficult to visit or from populations that are most likely extirpated has improved the geographic and temporal resolution of the mitochondrial phylogeny of baboons considerably. Our study also shows the great value of museum material for genetic analyses even when DNA is highly degraded.

Serosurvey of Treponema pallidum infection among children with skin ulcers in the Tarangire-Manyara ecosystem, northern Tanzania.

BACKGROUND: The first yaws eradication campaign reduced the prevalence of yaws by 95%. In recent years, however, yaws has reemerged and is currently subject to a second, ongoing eradication campaign. Yet, the epidemiological status of Tanzania and 75 other countries with a known history of human yaws is currently unknown. Contrary to the situation in humans in Tanzania, recent infection of nonhuman primates (NHPs) with the yaws bacterium Treponema pallidum subsp. pertenue (TPE) have been reported. In this study, we consider a One Health approach to investigate yaws and describe skin ulcers and corresponding T. pallidum serology results among children living in the Tarangire-Manyara ecosystem, an area with increasing wildlife-human interaction in northern Tanzania. METHODS: To investigate human yaws in Tanzania, we conducted a cross-sectional study to screen and interview skin-ulcerated children aged 6 to 15 years, who live in close proximity to two national parks with high numbers of naturally TPE-infected monkeys. Serum samples from children with skin ulcers were tested for antibodies against the bacterium using a treponemal (Treponema pallidum Particle Agglutination assay) and a non-treponemal (Rapid Plasma Reagin) test. RESULTS: A total of 186 children aged between 6 and 15 years (boys: 10.7 ± 2.1 (mean ± SD), N = 132; girls: 10.9 ± 2.0 (mean ± SD), N = 54) were enrolled. Seven children were sampled at health care facilities and 179 at primary schools. 38 children (20.4%) reported active participation in bushmeat hunting and consumption and 26 (13.9%) reported at least one physical contact with a NHP. None of the lesions seen were pathognomonic for yaws. Two children tested positive for treponemal antibodies (1.2%) in the treponemal test, but remained negative in the non-treponemal test. CONCLUSIONS: We found no serological evidence of yaws among children in the Tarangire-Manyara ecosystem. Nevertheless, the close genetic relationship of human and NHPs infecting TPE strains should lead to contact prevention with infected NHPs. Further research investigations are warranted to study the causes and possible prevention measures of spontaneous chronic ulcers among children in rural Tanzania and to certify that the country is free from human yaws.

Strain diversity of Treponema pallidum subsp. pertenue suggests rare interspecies transmission in African nonhuman primates.

In our most recent study, we found that in Tanzania infection with Treponema pallidum (TP) subsp. pertenue (TPE) is present in four different monkey species. In order to gain information on the diversity and epidemiological spread of the infection in Tanzanian nonhuman primates (NHP), we identified two suitable candidate genes for multi-locus sequence typing (MLST). We demonstrate the functionality of the MLST system in invasively and non-invasively collected samples. While we were not able to demonstrate frequent interspecies transmission of TPE in Tanzanian monkeys, our results show a clustering of TPE strains according to geography and not host species, which is suggestive for rare transmission events between different NHP species. In addition to the geographic stability, we describe the relative temporal stability of the strains infecting NHPs and identified multi-strain infection. Differences between TPE strains of NHP and human origin are highlighted. Our results show that antibiotic resistance does not occur in Tanzanian TPE strains of NHP origin.

Widespread Treponema pallidum Infection in Nonhuman Primates, Tanzania.

We investigated Treponema pallidum infection in 8 nonhuman primate species (289 animals) in Tanzania during 2015-2017. We used a serologic treponemal test to detect antibodies against the bacterium. Infection was further confirmed from tissue samples of skin-ulcerated animals by 3 independent PCRs (polA, tp47, and TP_0619). Our findings indicate that T. pallidum infection is geographically widespread in Tanzania and occurs in several species (olive baboons, yellow baboons, vervet monkeys, and blue monkeys). We found the bacterium at 11 of 14 investigated geographic locations. Anogenital ulceration was the most common clinical manifestation; orofacial lesions also were observed. Molecular data show that nonhuman primates in Tanzania are most likely infected with T. pallidum subsp. pertenue-like strains, which could have implications for human yaws eradication.

Gene target selection for loop-mediated isothermal amplification for rapid discrimination of Treponema pallidum subspecies.

We show proof of concept for gene targets (polA, tprL, and TP_0619) that can be used in loop-mediated isothermal amplification (LAMP) assays to rapidly differentiate infection with any of the three Treponema pallidum subspecies (pallidum (TPA), pertenue (TPE), and endemicum (TEN)) and which are known to infect humans and nonhuman primates (NHPs). Four TPA, six human, and two NHP TPE strains, as well as two human TEN strains were used to establish and validate the LAMP assays. All three LAMP assays were highly specific for the target DNA. Amplification was rapid (5-15 min) and within a range of 10E+6 to 10E+2 of target DNA molecules. Performance in NHP clinical samples was similar to the one seen in human TPE strains. The newly designed LAMP assays provide proof of concept for a diagnostic tool that enhances yaws clinical diagnosis. It is highly specific for the target DNA and does not require expensive laboratory equipment. Test results can potentially be interpreted with the naked eye, which makes it suitable for the use in remote clinical settings.

Inverted intergeneric introgression between critically endangered kipunjis and yellow baboons in two disjunct populations.

Intergeneric hybridization and introgression was reported from one of two populations of the recently discovered kipunji (Rungwecebus kipunji), a critically endangered African monkey species of southern Tanzania. Kipunjis of the introgressed population (from Mount Rungwe) carry a mitochondrial DNA (mtDNA) haplotype closely related to those of parapatric yellow baboons (Papio cynocephalus), whereas the second kipunji population, in the Udzungwa Mountains, carries the original kipunji mtDNA haplotypes, which diverged from the baboon lineage about 3 million years ago. Interestingly, in our study of yellow baboons in Tanzania, we found that baboons from the southeastern boundary of the Udzungwa Mountains carry mtDNA haplotypes closely related to the original kipunji haplotype, whereas baboons from the northern boundary, as expected, carry mtDNA haplotypes of the northern yellow baboon clade. These findings provide evidence for a case of inverted intergeneric admixture in primates: (i) a baboon mtDNA haplotype introgressed the Mount Rungwe kipunji population by mitochondrial capture and (ii) an Udzungwa Mountains kipunji mtDNA haplotype introgressed a small subpopulation of yellow baboons by either mitochondrial capture or nuclear swamping. The baboon-kipunji example therefore constitutes an interesting system for further studies of the effects of genetic admixture on fitness and speciation.

Complete mitochondrial genome of an olive baboon (Papio anubis) from Gombe National Park, Tanzania.

The olive baboon (Papio anubis) is the most widely distributed baboon species. We report here on the complete mitochondrial genome of an olive baboon from the south-eastern edge of the species' range from Gombe National Park (NP), Tanzania. The genome (GenBank accession number MG787545) has a length of 16,490 bp and exhibits the typical structure of mammalian mitochondrial genomes. Phylogenetically, the olive baboon from Gombe NP is most closely related to eastern P. anubis, northern P. cynocephalus and P. hamadryas. The data are an important addition to further clarify the phylogeography of baboons and phylogeny of papionins in general.