Gut microbiota variations in wild yellow baboons (Papio cynocephalus) are associated with sex and habitat disturbance.

Although male and female mammals differ in biological traits and functional needs, the contribution of this sexual dimorphism to variations in gut bacteria and fungi (gut microbiota) in relation to habitat type has not been fully examined. To understand whether the combination of sex and habitat affects gut microbiota variation, we analyzed 40 fecal samples of wild yellow baboons (Papio cynocephalus) living in contrasting habitat types (intact, well-protected vs. fragmented, less protected forests) in the Udzungwa Mountains of Tanzania. Sex determination was performed using the marker genes SRY (Sex-determining Region Y) and DDX3X-DDX3Y (DEAD-Box Helicase 3). Samples were attributed to 34 individuals (19 females and 15 males) belonging to five social groups. Combining the results of sex determination with two amplicon sequencing datasets on bacterial (V1-V3 region of the 16S rRNA gene) and fungal (ITS2) gut communities, we found that overall, baboon females had a significantly higher gut bacterial richness compared to males. Beta diversity estimates indicated that bacterial composition was significantly different between males and females, and this was true for individuals from both well- and less protected forests. Our results highlight the combined role of sex and habitat type in shaping variation in gut microbial communities in wild non-human primates.

Ecology and age, but not genetic ancestry, predict fetal loss in a wild baboon hybrid zone.

OBJECTIVES: Pregnancy failure represents a major fitness cost for any mammal, particularly those with slow life histories such as primates. Here, we quantified the risk of fetal loss in wild hybrid baboons, including genetic, ecological, and demographic sources of variance. We were particularly interested in testing the hypothesis that hybridization increases fetal loss rates. Such an effect would help explain how baboons may maintain genetic and phenotypic integrity despite interspecific gene flow. MATERIALS AND METHODS: We analyzed outcomes for 1020 pregnancies observed over 46 years in a natural yellow baboon-anubis baboon hybrid zone. Fetal losses and live births were scored based on records of female reproductive state and the appearance of live neonates. We modeled the probability of fetal loss as a function of a female's genetic ancestry (the proportion of her genome estimated to be descended from anubis [vs. yellow] ancestors), age, number of previous fetal losses, dominance rank, group size, climate, and habitat quality using binomial mixed effects models. RESULTS: Female genetic ancestry did not predict fetal loss. Instead, the risk of fetal loss is elevated for very young and very old females. Fetal loss is most robustly predicted by ecological factors, including poor habitat quality prior to a home range shift and extreme heat during pregnancy. DISCUSSION: Our results suggest that gene flow between yellow and anubis baboons is not impeded by an increased risk of fetal loss for hybrid females. Instead, ecological conditions and female age are key determinants of this component of female reproductive success.

High social status males experience accelerated epigenetic aging in wild baboons.

Aging, for virtually all life, is inescapable. However, within populations, biological aging rates vary. Understanding sources of variation in this process is central to understanding the biodemography of natural populations. We constructed a DNA methylation-based age predictor for an intensively studied wild baboon population in Kenya. Consistent with findings in humans, the resulting 'epigenetic clock' closely tracks chronological age, but individuals are predicted to be somewhat older or younger than their known ages. Surprisingly, these deviations are not explained by the strongest predictors of lifespan in this population, early adversity and social integration. Instead, they are best predicted by male dominance rank: high-ranking males are predicted to be older than their true ages, and epigenetic age tracks changes in rank over time. Our results argue that achieving high rank for male baboons - the best predictor of reproductive success - imposes costs consistent with a 'live fast, die young' life-history strategy.

For most animals, age is one of the strongest predictors of health and survival, but not all individuals age at the same rate. In fact, animals of the same species can have different 'biological ages' even when they have lived the same number of years. In humans and other mammals this variation in aging shows up in chemical modifications known as DNA methylation marks. Some researchers call these marks 'epigenetic', which literally means 'upon the genes'. And some DNA methylation marks change with age, so their combined pattern of change is often called the 'epigenetic clock'. Environmental stressors, such as smoking or lack of physical activity, can make the epigenetic clock 'tick' faster, making the DNA of some individuals appear older than expected based on their actual age in years. These 'biologically older' individuals may also experience a higher risk of age-related disease. Studies in humans have revealed some of the reasons behind this fast biological aging, but it is unclear whether these results apply in the wild. It is possible that early life events trigger changes in the epigenetic clock, affecting health in adulthood. In primates, for example, adversity in early life has known effects on fertility and survival. Low social status also has a negative effect on health. To find out whether early experiences and the social environment affect the epigenetic clock, Anderson, Johnston et al. tracked DNA methylation marks in baboons. This revealed that epigenetic clocks are strong predictors of age in wild primates, but neither early adversity nor the strength of social bonds affected the rate at which the clocks ticked. In fact, it was competition for social status that had the most dramatic effect on the clock's speed. Samples of males taken at different times during their lives showed that their epigenetic clocks sped up or slowed down as they moved up or down the social ladder, reflecting recent social experiences, rather than events early in their lives. On average, epigenetic clock measurements overestimated the age in years of alpha males by almost a year, showing that fighting to be on top comes at a cost. This study highlights one way in which the social environment can influence aging. The next step is to understand how health is affected by the ways that animals attain social status. This could help researchers who study evolution understand how social interactions and environmental conditions affect survival and reproduction. It could also provide insight into the effects of social status on human health and aging.

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.

Analysis of 100 high-coverage genomes from a pedigreed captive baboon colony.

Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely used as a nonhuman primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 yr. Unlike other model organisms, however, the genomic resources for baboons are severely lacking. This has hindered the progress of studies using baboons as a model for basic biology or human disease. Here, we describe a data set of 100 high-coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show how the data can be used to learn about ancestry and admixture and to correct errors in the colony records. Finally, we investigated the consequences of inbreeding within the SNPRC colony and found clear evidence for increased rates of infant mortality and increased homozygosity of putatively deleterious alleles in inbred individuals.

Restricted MHC class I A locus diversity in olive and hybrid olive/yellow baboons from the Southwest National Primate Research Center.

Baboons are valuable models for complex human diseases due to their genetic and physiologic similarities to humans. Deep sequencing methods to characterize full-length major histocompatibility complex (MHC) class I (MHC-I) alleles in different nonhuman primate populations were used to identify novel MHC-I alleles in baboons. We combined data from Illumina MiSeq sequencing and Roche/454 sequencing to characterize novel full-length MHC-I transcripts in a cohort of olive and hybrid olive/yellow baboons from the Southwest National Primate Research Center (SNPRC). We characterized 57 novel full-length alleles from 24 baboons and found limited genetic diversity at the MHC-I A locus, with significant sharing of two MHC-I A lineages between 22 out of the 24 animals characterized. These shared alleles provide the basis for development of tools such as MHC:peptide tetramers for studying cellular immune responses in this important animal model.

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.

Genomewide ancestry and divergence patterns from low-coverage sequencing data reveal a complex history of admixture in wild baboons.

Naturally occurring admixture has now been documented in every major primate lineage, suggesting its key role in primate evolutionary history. Active primate hybrid zones can provide valuable insight into this process. Here, we investigate the history of admixture in one of the best-studied natural primate hybrid zones, between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in the Amboseli ecosystem of Kenya. We generated a new genome assembly for yellow baboon and low-coverage genomewide resequencing data from yellow baboons, anubis baboons and known hybrids (n = 44). Using a novel composite likelihood method for estimating local ancestry from low-coverage data, we found high levels of genetic diversity and genetic differentiation between the parent taxa, and excellent agreement between genome-scale ancestry estimates and a priori pedigree, life history and morphology-based estimates (r(2)  = 0.899). However, even putatively unadmixed Amboseli yellow individuals carried a substantial proportion of anubis ancestry, presumably due to historical admixture. Further, the distribution of shared vs. fixed differences between a putatively unadmixed Amboseli yellow baboon and an unadmixed anubis baboon, both sequenced at high coverage, is inconsistent with simple isolation-migration or equilibrium migration models. Our findings suggest a complex process of intermittent contact that has occurred multiple times in baboon evolutionary history, despite no obvious fitness costs to hybrids or major geographic or behavioural barriers. In combination with the extensive phenotypic data available for baboon hybrids, our results provide valuable context for understanding the history of admixture in primates, including in our own lineage.

Resource base influences genome-wide DNA methylation levels in wild baboons (Papio cynocephalus).

Variation in resource availability commonly exerts strong effects on fitness-related traits in wild animals. However, we know little about the molecular mechanisms that mediate these effects, or about their persistence over time. To address these questions, we profiled genome-wide whole-blood DNA methylation levels in two sets of wild baboons: (i) 'wild-feeding' baboons that foraged naturally in a savanna environment and (ii) 'Lodge' baboons that had ready access to spatially concentrated human food scraps, resulting in high feeding efficiency and low daily travel distances. We identified 1014 sites (0.20% of sites tested) that were differentially methylated between wild-feeding and Lodge baboons, providing the first evidence that resource availability shapes the epigenome in a wild mammal. Differentially methylated sites tended to occur in contiguous stretches (i.e., in differentially methylated regions or DMRs), in promoters and enhancers, and near metabolism-related genes, supporting their functional importance in gene regulation. In agreement, reporter assay experiments confirmed that methylation at the largest identified DMR, located in the promoter of a key glycolysis-related gene, was sufficient to causally drive changes in gene expression. Intriguingly, all dispersing males carried a consistent epigenetic signature of their membership in a wild-feeding group, regardless of whether males dispersed into or out of this group as adults. Together, our findings support a role for DNA methylation in mediating ecological effects on phenotypic traits in the wild and emphasize the dynamic environmental sensitivity of DNA methylation levels across the life course.

Further evidence for phenotypic signatures of hybridization in descendant baboon populations.

Hybridization may have played a substantial role in shaping the diversity of our evolving lineage. Although recent genomic evidence has shown that hybridization occurred between anatomically modern humans (AMHS) and Neanderthals, it remains difficult to pin down precisely where and when this gene flow took place. Investigations of the hybrid phenotype in primates and other mammals are providing models for identifying signatures of hybridization in the fossil record. However, our understanding of intra- and inter-taxon variation in hybrids is still limited. Moreover, there is little evidence from these studies that is pertinent to the question of how long hybrid skeletal traits persist in descendants, and therefore it is not clear whether observed hybrid phenotypes are evidence of recent (e.g., F1) or much earlier hybridization events. Here, we present an analysis updating a previous study of cranial variation in pedigreed olive and yellow baboons and their hybrids. Results suggest that traits previously associated with hybrids in baboons and other mammalian species are also present in this expanded data set; many of these traits are highly heritable, confirming a genetic basis for their variation in this mixed population. While F1 animals - and especially F1 males - still have the highest number of dental anomalies, these and other atypical traits persist into later hybrid generations (such as F2 and B1). Moreover, non-F1 recombinants also show extremely rare trait variations, including reduced canines and rotated teeth. However, these results must be considered in light of the possibility that some founding individuals may have themselves been unrecognized hybrids. Despite this, the data are compelling, and indicate once again that further controlled research remains to be done on primates and other mammals in order to better understand variation in the hybrid phenotype.

Evolution of a malaria resistance gene in wild primates.

The ecology, behaviour and genetics of our closest living relatives, the nonhuman primates, should help us to understand the evolution of our own lineage. Although a large amount of data has been amassed on primate ecology and behaviour, much less is known about the functional and evolutionary genetic aspects of primate biology, especially in wild primates. As a result, even in well-studied populations in which nongenetic factors that influence adaptively important characteristics have been identified, we have almost no understanding of the underlying genetic basis for such traits. Here, we report on the functional consequences of genetic variation at the malaria-related FY (DARC) gene in a well-studied population of yellow baboons (Papio cynocephalus) living in Amboseli National Park in Kenya. FY codes for a chemokine receptor normally expressed on the erythrocyte surface that is the known entry point for the malarial parasite Plasmodium vivax. We identified variation in the cis-regulatory region of the baboon FY gene that was associated with phenotypic variation in susceptibility to Hepatocystis, a malaria-like pathogen that is common in baboons. Genetic variation in this region also influenced gene expression in vivo in wild individuals, a result we confirmed using in vitro reporter gene assays. The patterns of genetic variation in and around this locus were also suggestive of non-neutral evolution, raising the possibility that the evolution of the FY cis-regulatory region in baboons has exhibited both mechanistic and selective parallels with the homologous region in humans. Together, our results represent the first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates.

LRP5 sequence and polymorphisms in the baboon.

BACKGROUND: LRP5 is known to have an important relationship with bone density and a variety of other biological processes. Mapping to human chromosome 11q13.2, LRP5 shows considerable evolutionary conservation. Orthologs of this gene exist in many species, although comparison of human LRP5 with other non-human primates has not been performed until now. METHODS: We reported the complementary DNA (cDNA) sequence and deduced amino acid sequence for baboon LRP5, and compared the baboon and human sequences. cDNA sequences for 21 baboons were examined to identify single-nucleotide polymorphisms (SNPs). RESULTS: Sequences of coding regions in human and baboon LRP5 showed 97- 99% homology. Twenty-five SNPs were identified in the coding region of baboon LRP5. CONCLUSION: The observed degree of coding sequence homology in LRP5 led us to expect that the baboon may serve as a useful model for future research into the role(s) of this gene in primate metabolic diseases.

Age at maturity in wild baboons: genetic, environmental and demographic influences.

The timing of early life-history events, such as sexual maturation and first reproduction, can greatly influence variation in individual fitness. In this study, we analysed possible sources of variation underlying different measures of age at social and physical maturation in wild baboons in the Amboseli basin, Kenya. The Amboseli baboons are a natural population primarily comprised of yellow baboons (Papio cynocephalus) that occasionally hybridize with anubis baboons (Papio anubis) from outside the basin. We found that males and females differed in the extent to which various factors influenced their maturation. Surprisingly, we found that male maturation was most strongly related to the proportion of anubis ancestry revealed by their microsatellite genotypes: hybrid males matured earlier than yellow males. In contrast, although hybrid females reached menarche slightly earlier than yellow females, maternal rank and the presence of maternal relatives had the largest effects on female maturation, followed by more modest effects of group size and rainfall. Our results indicate that a complex combination of demographic, genetic, environmental, and maternal effects contribute to variation in the timing of these life-history milestones.

Genetic evidence reveals temporal change in hybridization patterns in a wild baboon population.

The process and consequences of hybridization are of interest to evolutionary biologists because of the importance of hybridization in understanding reproductive isolation, speciation, and the influence of introgression on population genetic structure. Recent studies of hybridization have been enhanced by the advent of sensitive, genetic marker-based techniques for inferring the degree of admixture occurring within individuals. Here we present a genetic marker-based analysis of hybridization in a large-bodied, long-lived mammal over multiple generations. We analysed patterns of hybridization between yellow baboons (Papio cynocephalus) and anubis baboons (Papio anubis) in a well-studied natural population in Amboseli National Park, Kenya, using genetic samples from 450 individuals born over the last 36 years. We assigned genetic hybrid scores based on genotypes at 14 microsatellite loci using the clustering algorithm implemented in STRUCTURE 2.0, and assessed the robustness of these scores by comparison to pedigree information and through simulation. The genetic hybrid scores showed generally good agreement with previous morphological assessments of hybridity, but suggest that genetic methods may be more sensitive for identification of low levels of hybridity. The results of our analysis indicate that the proportion of hybrids in the Amboseli population has grown over time, but that the average proportion of anubis ancestry within hybrids is gradually decreasing. We argue that these patterns are probably a result of both selective and nonselective processes, including differences in the timing of life-history events for hybrid males relative to yellow baboon males, and stochasticity in long-distance dispersal from the source anubis population into Amboseli.

Prostaglandin E2 receptor expression in fetal baboon lung at 0.7 gestation after betamethasone exposure.

The fetal lung produces and metabolizes prostaglandin (PG) E2. In vitro PGE2 induces surfactant production via E prostaglandin (EP)1 and cyclic adenosine monophosphate (cAMP)-coupled EP (EP2 and EP4) receptors. Glucocorticoids alter PG function and increase lung function in preterm neonates. We hypothesized that fetal exposure to maternally administered betamethasone (betaM) enhances fetal lung EP1 and cAMP-coupled EP receptor expression. Pregnant baboons were injected intramuscularly (i.m.) with either betaM (n=7) or saline [control (CTR); n=8] at 0.7 gestation. Fetal lungs were removed at cesarean section 48 h after the first injection. We determined mRNA levels, protein localization and abundance for all four PGE2 receptors by real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. EP receptors were widely distributed in bronchiolar epithelium, bronchiolar smooth muscle, and endothelium and media of blood vessels, but not alveoli. Compared with CTR, betaM exposure resulted in a twofold EP2 mRNA decrease (p<0.05) in male fetuses only. EP1, EP3, and EP4 receptor mRNA levels were unaffected. Western blot analysis showed no alteration in EP receptor protein expression. In summary, this is the first demonstration of the four EP receptors in fetal lung. The only change after 48-h betaM exposure was a gender-specific decrease in EP2 receptor mRNA.

Indels and imperfect duplication have driven the evolution of human Complement Receptor 1 (CR1) and CR1-like from their precursor CR1 alpha: importance of functional sets.

This study examines the effects of duplication and insertions-deletions (indels) by comparing human complement receptor 1 (CR1) and human CR1-like (CR1L) with syntenic genes from four other vertebrates (chimpanzee, baboon, rat, and mouse). By phylogenetic analysis, the domains of these genes can be classified into 10 distinct subfamilies (a, b, c, d, e, f, g(-like), h, j, and k), which have been largely conserved throughout vertebrate and invertebrate evolution. In spite of many complex and diverse duplications and indels, the subfamily order of domains (a, j, e, f, b, k, d, g(-like)) has been maintained. The number of domain sets has increased progressively, thereby expanding the functional repertoire.