-
Scientific Reports Aug 2023Y chromosome markers can shed light on male-specific population dynamics but for many species no such markers have been discovered and are available yet, despite the...
Y chromosome markers can shed light on male-specific population dynamics but for many species no such markers have been discovered and are available yet, despite the potential for recovering Y-linked loci from available genome sequences. Here, we investigated how effective available bioinformatic tools are in recovering informative Y chromosome microsatellites from whole genome sequence data. In order to do so, we initially explored a large dataset of whole genome sequences comprising individuals at various coverages belonging to different species of baboons (genus: Papio) using Y chromosome references belonging to the same genus and more distantly related species (Macaca mulatta). We then further tested this approach by recovering Y-STRs from available Theropithecus gelada genomes using Papio and Macaca Y chromosome as reference sequences. Identified loci were validated in silico by a) comparing within-species relationships of Y chromosome lineages and b) genotyping male individuals in available pedigrees. Each STR was selected not to extend in its variable region beyond 100 base pairs, so that loci can be developed for PCR-based genotyping of non-invasive DNA samples. In addition to assembling a first set of Papio and Theropithecus Y-specific microsatellite markers, we released TYpeSTeR, an easy-to-use script to identify and genotype Y chromosome STRs using population genomic data which can be modulated according to available male reference genomes and genomic data, making it widely applicable across taxa.
Topics: Humans; Male; Animals; Metagenomics; Theropithecus; Papio; Macaca mulatta; Microsatellite Repeats
PubMed: 37620368
DOI: 10.1038/s41598-023-40931-x -
Proceedings of the National Academy of... Mar 2024Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the evolutionary...
Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the evolutionary dynamics within hybrid populations that underlie these patterns have been lacking. Due to the clock-like effect of recombination in hybrids breaking up parental haplotypes, drift and selection produce predictable patterns of ancestry variation at varying spatial genomic scales through time. Here, we develop methods based on the Discrete Wavelet Transform to study the genomic scale of local ancestry variation and its association with recombination rates and show that these methods capture temporal dynamics of drift and genome-wide selection after hybridization. We apply these methods to published datasets from hybrid populations of swordtail fish () and baboons () and to inferred Neanderthal introgression in modern humans. Across systems, upward of 20% of variation in local ancestry at the broadest genomic scales can be attributed to systematic selection against introgressed alleles, consistent with strong selection acting on early-generation hybrids. Signatures of selection at fine genomic scales suggest selection over longer time scales; however, we suggest that our ability to confidently infer selection at fine scales is likely limited by inherent biases in current methods for estimating local ancestry from contiguous segments of genomic similarity. Wavelet approaches will become widely applicable as genomic data from systems with introgression become increasingly available and can help shed light on generalities of the genomic consequences of interspecific hybridization.
Topics: Animals; Humans; Genome; Genomics; Hybridization, Genetic; Nucleic Acid Hybridization; Haplotypes; Neanderthals; Selection, Genetic
PubMed: 38489387
DOI: 10.1073/pnas.2309168121 -
Frontiers in Immunology 2023Circadian rhythms broadly impact human health by regulating our daily physiological and metabolic processes. The circadian clocks substantially regulate our immune...
BACKGROUND
Circadian rhythms broadly impact human health by regulating our daily physiological and metabolic processes. The circadian clocks substantially regulate our immune responses and susceptibility to infections. Malaria parasites have intrinsic molecular oscillations and coordinate their infection cycle with host rhythms. Considering the cyclical nature of malaria, a clear understanding of the circadian regulations in malaria pathogenesis and host responses is of immense importance.
METHODS
We have thoroughly investigated the transcript level rhythmic patterns in blood proteins altered in falciparum and vivax malaria and malaria-related immune factors in mice, baboons, and humans by analyzing datasets from published literature and comprehensive databases. Using the Metascape and DAVID platforms, we analyzed Gene Ontology terms and physiological pathways associated with the rhythmic malaria-associated host immune factors.
RESULTS
We observed that almost 50% of the malaria-associated host immune factors are rhythmic in mice and humans. Overlapping rhythmic genes identified in mice, baboons, and humans, exhibited enrichment (Q < 0.05, fold-enrichment > 5) of multiple physiological pathways essential for host immune and defense response, including cytokine production, leukocyte activation, cellular defense, and response, regulation of kinase activity, B-cell receptor signaling pathway, and cellular response to cytokine stimulus.
CONCLUSIONS
Our analysis indicates a robust circadian regulation on multiple interconnected host response pathways and immunological networks in malaria, evident from numerous rhythmic genes involved in those pathways. Host immune rhythms play a vital role in the temporal regulation of host-parasite interactions and defense machinery in malaria.
Topics: Humans; Animals; Mice; Circadian Clocks; Malaria; Immunologic Factors; Cytokines; Papio
PubMed: 37638001
DOI: 10.3389/fimmu.2023.1210299 -
The Journal of Infectious Diseases Feb 2024The United States has experienced a resurgence of pertussis following the introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP...
BACKGROUND
The United States has experienced a resurgence of pertussis following the introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP vaccines to induce durable immunity and prevent infection, carriage, and transmission.
METHODS
To evaluate the impact of aP vaccination on the immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with Bordetella pertussis multiple times and accessed the immune responses and outcomes of infections after each exposure.
RESULTS
Multiple infections were required to elicit T-helper 17 responses and protection in aP-vaccinated animals comparable to responses seen in unvaccinated animals after a single challenge. Even after 3 challenges, T-helper 1 responses were not observed in aP-vaccinated animals. Immunoglobulin G responses to vaccine and nonvaccine antigens were not negatively affected in aP-vaccinated animals.
CONCLUSIONS
Our results indicate that it is possible to retrain aP-primed immune responses, but it will likely require an optimal booster and multiple doses. Our results in the baboon model suggest that circulation of B. pertussis in aP-vaccinated populations is concentrated in the younger age bands of the population, providing information that can guide improved modeling of B. pertussis epidemiology in aP-vaccinated populations.
Topics: Animals; Whooping Cough; Bordetella pertussis; Papio; Antibodies, Bacterial; Pertussis Vaccine; Vaccines, Acellular
PubMed: 37565807
DOI: 10.1093/infdis/jiad332 -
Reproductive Sciences (Thousand Oaks,... Oct 2023MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the...
MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the role of miR-210 and its targets, IGFBP3 and COL8A1, in ectopic lesion growth and development. Matched eutopic (EuE) and ectopic (EcE) endometrial samples were obtained for analysis from baboons and women with endometriosis. Immortalized human ectopic endometriotic epithelial cells (12Z cells) were utilized for functional assays. Endometriosis was experimentally induced in female baboons (n = 5). Human matched endometrial and endometriotic tissues were obtained from women (n = 9, 18-45 years old) with regular menstrual cycles. Quantitative reverse transcript polymerase chain reaction (RT-qPCR) analysis was performed for in vivo characterization of miR-210, IGFBP3, and COL8A1. In situ hybridization and immunohistochemical analysis were performed for cell-specific localization. Immortalized endometriotic epithelial cell lines (12Z) were utilized for in vitro functional assays. MiR-210 expression was decreased in EcE, while IGFBP3 and COL8A1 expression was increased in EcE. MiR-210 was expressed in the glandular epithelium of EuE but attenuated in those of EcE. IGFBP3 and COL8A1 were expressed in the glandular epithelium of EuE and were increased compared to EcE. MiR-210 overexpression in 12Z cells suppressed IGFBP3 expression and attenuated cell proliferation and migration. MiR-210 repression and subsequent unopposed IGFBP3 expression may contribute to endometriotic lesion development by increasing cell proliferation and migration.
Topics: Animals; Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Endometriosis; Papio; MicroRNAs; Endometrium; Cell Line; Insulin-Like Growth Factor Binding Protein 3
PubMed: 37188982
DOI: 10.1007/s43032-023-01253-5 -
IScience Jul 2023Reproductive strategies are defined by expenditures of time and energy devoted to mating effort, which increases mating opportunities, and parenting effort, which...
Reproductive strategies are defined by expenditures of time and energy devoted to mating effort, which increases mating opportunities, and parenting effort, which enhances the survival of offspring. We examine tradeoffs between mating effort and parenting effort in male olive baboons, , a species in which males compete for mating opportunities, but also form ties to lactating females (primary associations) that represent a form of parenting effort. Males that are involved in more primary associations invest less in mating effort than males who are involved in fewer primary associations. Males that are involved in more primary associations play a smaller role in establishing proximity to their primary associates than other males, suggesting that males operate under temporal constraints. There is also some evidence that involvement in primary associations negatively affects paternity success. Taken together, the data suggest that males face tradeoffs between mating effort and parenting effort.
PubMed: 37534148
DOI: 10.1016/j.isci.2023.106991 -
Nature Communications Jun 2024The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready...
The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready brain. However, studies have reported a similar structural PT left-asymmetry not only in various adult non-human primates, but also in newborn baboons. Its shared functional links with language are not fully understood. Here we demonstrate using previously obtained MRI data that early detection of PT left-asymmetry among 27 newborn baboons (Papio anubis, age range of 4 days to 2 months) predicts the future development of right-hand preference for communicative gestures but not for non-communicative actions. Specifically, only newborns with a larger left-than-right PT were more likely to develop a right-handed communication once juvenile, a contralateral brain-gesture link which is maintained in a group of 70 mature baboons. This finding suggests that early PT asymmetry may be a common inherited prewiring of the primate brain for the ontogeny of ancient lateralised properties shared between monkey gesture and human language.
Topics: Animals; Functional Laterality; Gestures; Animals, Newborn; Magnetic Resonance Imaging; Female; Male; Papio anubis; Temporal Lobe; Language
PubMed: 38839754
DOI: 10.1038/s41467-024-47277-6 -
Scientific Reports Dec 2023Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated...
Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated intravascular coagulation, and their potential treatment with novel drugs. Thrombin generation is vital for these models, and an important potential therapeutic target. We investigated the thrombin generation profile of the Chacma baboon (Papio ursinus - a common pre-clinical model) including the effects of sex and ABO blood group. Thrombin generation curves, lag times, peak heights, times-to-peak, velocity indexes and Endogenous Thrombin Potentials (ETPs) of 40 adult Chacma baboons were assessed and compared with normal human plasma, using a low concentration of tissue factor (1 pM) and phospholipids. Reference intervals were calculated, and results compared between O and non-O ABO blood groups, and between males and females. Lag times of all baboons fell within the human reference interval. Most animals (n = 32; 80%) had times-to-peak above, and velocity indexes and peak heights markedly below (n = 27; 68%) the human range. However, 97.5% of baboons had an ETP above the human reference interval, indicating greater overall thrombin generation. ABO blood group had no effect, but males (n = 14; 35%) had less potent thrombin generation than females (n = 26; 65%), with significantly longer lag times (p = 0.0475), lower peak thrombin concentrations (p = 0.0203), and lower ETPs (p = 0.0238). Chacma baboons have greater overall endogenous thrombin generation potentials than humans, which is even more prominent in females. This should be considered when designing future baboon model experiments involving the haemostatic system, or when evaluating novel therapies in these animals.
Topics: Male; Animals; Female; Humans; Papio ursinus; Thrombin; Hemostatics; ABO Blood-Group System; Papio
PubMed: 38151511
DOI: 10.1038/s41598-023-50341-8 -
Viruses Jul 2023Xenotransplantation, like allotransplantation, is usually associated with microchimerism, i.e., the presence of cells from the donor in the recipient. Microchimerism was...
Xenotransplantation, like allotransplantation, is usually associated with microchimerism, i.e., the presence of cells from the donor in the recipient. Microchimerism was reported in first xenotransplantation trials in humans, as well as in most preclinical trials in nonhuman primates (for review, see Denner, Viruses 2023, 15, 190). When using pigs as xenotransplantation donors, their cells contain porcine endogenous retroviruses (PERVs) in their genome. This makes it difficult to discriminate between microchimerism and PERV infection of the recipient. Here, we demonstrate the appropriate virological methods to be used for the identification of microchimerism, first by screening for porcine cellular genes, and then how to detect infection of the host. Using porcine short interspersed nuclear sequences (SINEs), which have hundreds of thousands of copies in the pig genome, significantly increased the sensitivity of the screening for pig cells. Second, absence of PERV RNA demonstrated an absence of viral genomic RNA or expression as mRNA. Lastly, absence of antibodies against PERV proteins conclusively demonstrated an absence of a PERV infection. When applying these methods for analyzing baboons after pig heart transplantation, microchimerism could be demonstrated and infection excluded in all animals. These methods can be used in future clinical trials.
Topics: Humans; Swine; Animals; Papio; Chimerism; Endogenous Retroviruses; Transplantation, Heterologous; RNA
PubMed: 37515304
DOI: 10.3390/v15071618 -
Blood Advances Aug 2023Increased fetal hemoglobin (HbF) levels reduce the symptoms of sickle cell disease (SCD) and increase the lifespan of patients. Because curative strategies for bone...
Increased fetal hemoglobin (HbF) levels reduce the symptoms of sickle cell disease (SCD) and increase the lifespan of patients. Because curative strategies for bone marrow transplantation and gene therapy technologies remain unavailable to a large number of patients, the development of a safe and effective pharmacological therapy that increases HbF offers the greatest potential for disease intervention. Although hydroxyurea increases HbF, a substantial proportion of patients fail to demonstrate an adequate response. Pharmacological inhibitors of DNA methyltransferase (DNMT1) and lysine-specific demethylase 1A (LSD1), 2 epigenome-modifying enzymes associated with the multiprotein corepressor complex recruited to the repressed γ-globin gene, are powerful in vivo inducers of HbF. The hematological side effects of these inhibitors limit feasible clinical exposures. We evaluated whether administering these drugs in combination could reduce the dose and/or time of exposure to any single agent to minimize adverse effects, while achieving additive or synergistic increases in HbF. The DNMT1 inhibitor decitabine (0.5 mg/kg per day) and the LSD1 inhibitor RN-1 (0.25 mg/kg per day) administered in combination 2 days per week produced synergistic increases in F-cells, F-reticulocytes, and γ-globin messenger RNA in healthy baboons. Large increases in HbF and F-cells were observed in healthy, nonanemic, and anemic (phlebotomized) baboons. Combinatorial therapy targeting epigenome-modifying enzymes could thus be a useful strategy for producing larger increases in HbF to modify the clinical course of SCD.
Topics: Humans; Animals; Decitabine; gamma-Globins; Epigenome; Fetal Hemoglobin; Anemia, Sickle Cell; Papio; Histone Demethylases
PubMed: 36884303
DOI: 10.1182/bloodadvances.2022009558