Common cold viruses circulating in children threaten wild chimpanzees through asymptomatic adult carriers.

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.

Functional fixedness in chimpanzees.

Differences in the tool use of non-human primates and humans are subject of ongoing debate. In humans, representations of object functions underpin efficient tool use. Yet, representations of object functions can lead to functional fixedness, which describes the fixation on a familiar tool function leading to less efficient problem solving when the problem requires using the tool for a new function. In the current study, we examined whether chimpanzees exhibit functional fixedness. After solving a problem with a tool, chimpanzees were less efficient in solving another problem which required using the same tool with a different function compared to a control group. This fixation effect was still apparent after a period of nine months and when chimpanzees had learned about the function of a tool by observation of a conspecific. These results suggest that functional fixedness in our closest living relatives likely exists and cast doubt on the notion that stable function representations are uniquely human.

Animal behavior: A tale of two apes.

A new paper shows that rates of aggression are higher, and rates of coalition formation are lower, among male bonobos than among male chimpanzees. These findings are noteworthy because they challenge the view that female bonobos' preferences for less aggressive males favored a reduction in male aggression and an increase in social tolerance.

The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing.

The aryl hydrocarbon receptor (AHR) is a transcription factor that has many functions in mammals. Its best known function is that it binds aromatic hydrocarbons and induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons and other substrates. All present-day humans carry an amino acid substitution at position 381 in the AHR that occurred after the divergence of modern humans from Neandertals and Denisovans. Previous studies that have expressed the ancestral and modern versions of AHR from expression vectors have yielded conflicting results with regard to their activities. Here, we use genome editing to modify the endogenous AHR gene so that it encodes to the ancestral, Neandertal-like AHR protein in human cells. In the absence of exogenous ligands, the expression of AHR target genes is higher in cells expressing the ancestral AHR than in cells expressing the modern AHR, and similar to the expression in chimpanzee cells. Furthermore, the modern human AHR needs higher doses of three ligands than the ancestral AHR to induce the expression of target genes. Thus, the ability of AHR to induce the expression of many of its target genes is reduced in modern humans.

What's special about human speech? A student exercise for comparing speech production between humans and chimpanzees.

Modern humans and chimpanzees share a common ancestor on the phylogenetic tree, yet chimpanzees do not spontaneously produce speech or speech sounds. The lab exercise presented in this paper was developed for undergraduate students in a course entitled "What's Special About Human Speech?" The exercise is based on acoustic analyses of the words "cup" and "papa" as spoken by Viki, a home-raised, speech-trained chimpanzee, as well as the words spoken by a human. The analyses allow students to relate differences in articulation and vocal abilities between Viki and humans to the known anatomical differences in their vocal systems. Anatomical and articulation differences between humans and Viki include (1) potential tongue movements, (2) presence or absence of laryngeal air sacs, (3) presence or absence of vocal membranes, and (4) exhalation vs inhalation during production.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Long non-coding RNAs expression and regulation across different brain regions in primates.

Human and non-human primates have strikingly similar genomes, but they strongly differ in many brain-based processes (e.g., behaviour and cognition). While the functions of protein-coding genes have been extensively studied, rather little is known about the role of non-coding RNAs such as long non-coding RNAs (lncRNAs). Here, we predicted lncRNAs and analysed their expression pattern across different brain regions of human and non-human primates (chimpanzee, gorilla, and gibbon). Our analysis identified shared orthologous and non-orthologous lncRNAs, showing striking differences in the genomic features. Differential expression analysis of the shared orthologous lncRNAs from humans and chimpanzees revealed distinct expression patterns in subcortical regions (striatum, hippocampus) and neocortical areas while retaining a homogeneous expression in the cerebellum. Co-expression analysis of lncRNAs and protein-coding genes revealed massive proportions of co-expressed pairs in neocortical regions of humans compared to chimpanzees. Network analysis of co-expressed pairs revealed the distinctive role of the hub-acting orthologous lncRNAs in a region- and species-specific manner. Overall, our study provides novel insight into lncRNA driven gene regulatory landscape, neural regulation, brain evolution, and constitutes a resource for primate's brain lncRNAs.

Cardiac differentiation of chimpanzee induced pluripotent stem cell lines with different subspecies backgrounds.

The comparative analysis between humans and non-human primates is an instrumental approach for elucidating the evolutional traits and disease propensity of humans. However, in primates, cross-species analyses of their developmental events have encountered constraints because of the ethical and technical limitations in available sample collection, sequential monitoring, and manipulations. In an endeavor to surmount these challenges, in recent years, induced pluripotent stem cells (iPSCs) have garnered escalating interest as an in vitro tool for cross-species analyses between humans and non-human primates. Meanwhile, compared to humans, there is less information on in vitro differentiation of non-human primate iPSCs, and their genetic diversity including subspecies may cause different eligibility to in vitro differentiation methods. Therefore, antecedent to embarking on a comparative analysis to humans, it is a prerequisite to develop the efficacious methodologies for in vitro differentiation regardless of the intraspecies genetic background in non-human primates. In this study, we executed the in vitro differentiation of cardiomyocytes from four chimpanzee iPSC lines with different subspecies and individual backgrounds. To induce cardiomyocytes from chimpanzee iPSCs, we evaluated our methodology for in vitro cardiac differentiation of human iPSCs. Eventually, with minor alterations, our cardiac differentiation method was applicable to all chimpanzee iPSC lines tested as assessed by the expression of cardiac marker genes and the beating ability. Hence, our in vitro differentiation method will advance iPSC-based research of chimpanzee cardiac development and also hold possible utility to cross-species analyses among primate species.

Protracted development of stick tool use skills extends into adulthood in wild western chimpanzees.

Tool use is considered a driving force behind the evolution of brain expansion and prolonged juvenile dependency in the hominin lineage. However, it remains rare across animals, possibly due to inherent constraints related to manual dexterity and cognitive abilities. In our study, we investigated the ontogeny of tool use in chimpanzees (Pan troglodytes), a species known for its extensive and flexible tool use behavior. We observed 70 wild chimpanzees across all ages and analyzed 1,460 stick use events filmed in the Taï National Park, Côte d'Ivoire during the chimpanzee attempts to retrieve high-nutrient, but difficult-to-access, foods. We found that chimpanzees increasingly utilized hand grips employing more than 1 independent digit as they matured. Such hand grips emerged at the age of 2, became predominant and fully functional at the age of 6, and ubiquitous at the age of 15, enhancing task accuracy. Adults adjusted their hand grip based on the specific task at hand, favoring power grips for pounding actions and intermediate grips that combine power and precision, for others. Highly protracted development of suitable actions to acquire hidden (i.e., larvae) compared to non-hidden (i.e., nut kernel) food was evident, with adult skill levels achieved only after 15 years, suggesting a pronounced cognitive learning component to task success. The prolonged time required for cognitive assimilation compared to neuromotor control points to selection pressure favoring the retention of learning capacities into adulthood.

A shared pattern of midfacial bone modelling in hominids suggests deep evolutionary roots for human facial morphogenesis.

Midfacial morphology varies between hominoids, in particular between great apes and humans for which the face is small and retracted. The underlying developmental processes for these morphological differences are still largely unknown. Here, we investigate the cellular mechanism of maxillary development (bone modelling, BM), and how potential changes in this process may have shaped facial evolution. We analysed cross-sectional developmental series of gibbons, orangutans, gorillas, chimpanzees and present-day humans (n = 183). Individuals were organized into five age groups according to their dental development. To visualize each species's BM pattern and corresponding morphology during ontogeny, maps based on microscopic data were mapped onto species-specific age group average shapes obtained using geometric morphometrics. The amount of bone resorption was quantified and compared between species. Great apes share a highly similar BM pattern, whereas gibbons have a distinctive resorption pattern. This suggests a change in cellular activity on the hominid branch. Humans possess most of the great ape pattern, but bone resorption is high in the canine area from birth on, suggesting a key role of canine reduction in facial evolution. We also observed that humans have high levels of bone resorption during childhood, a feature not shared with other apes.

The work to swing limbs in humans versus chimpanzees and its relation to the metabolic cost of walking.

Compared to their closest ape relatives, humans walk bipedally with lower metabolic cost (C) and less mechanical work to move their body center of mass (external mechanical work, WEXT). However, differences in WEXT are not large enough to explain the observed lower C: humans may also do less work to move limbs relative to their body center of mass (internal kinetic mechanical work, WINT,k). From published data, we estimated differences in WINT,k, total mechanical work (WTOT), and efficiency between humans and chimpanzees walking bipedally. Estimated WINT,k is ~ 60% lower in humans due to changes in limb mass distribution, lower stride frequency and duty factor. When summing WINT,k to WEXT, between-species differences in efficiency are smaller than those in C; variations in WTOT correlate with between-species, but not within-species, differences in C. These results partially support the hypothesis that the low cost of human walking is due to the concerted low WINT,k and WEXT.

Selective deforestation and exposure of African wildlife to bat-borne viruses.

Proposed mechanisms of zoonotic virus spillover often posit that wildlife transmission and amplification precede human outbreaks. Between 2006 and 2012, the palm Raphia farinifera, a rich source of dietary minerals for wildlife, was nearly extirpated from Budongo Forest, Uganda. Since then, chimpanzees, black-and-white colobus, and red duiker were observed feeding on bat guano, a behavior not previously observed. Here we show that guano consumption may be a response to dietary mineral scarcity and may expose wildlife to bat-borne viruses. Videos from 2017-2019 recorded 839 instances of guano consumption by the aforementioned species. Nutritional analysis of the guano revealed high concentrations of sodium, potassium, magnesium and phosphorus. Metagenomic analyses of the guano identified 27 eukaryotic viruses, including a novel betacoronavirus. Our findings illustrate how "upstream" drivers such as socioeconomics and resource extraction can initiate elaborate chains of causation, ultimately increasing virus spillover risk.

Differences in expression of male aggression between wild bonobos and chimpanzees.

Researchers investigating the evolution of human aggression look to our closest living relatives, bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), as valuable sources of comparative data.1,2 Males in the two species exhibit contrasting patterns: male chimpanzees sexually coerce females3,4,5,6,7,8 and sometimes kill conspecifics,9,10,11,12 whereas male bonobos exhibit less sexual coercion13,14 and no reported killing.13 Among the various attempts to explain these species differences, the self-domestication hypothesis proposes negative fitness consequences of male aggression in bonobos.2,15,16 Nonetheless, the extent to which these species differ in overall rates of aggression remains unclear due to insufficiently comparable observation methods.17,18,19,20,21,22,23 We used 14 community-years of focal follow data-the gold standard for observational studies24-to compare rates of male aggression in 3 bonobo communities at the Kokolopori Bonobo Reserve, Democratic Republic of Congo, and 2 chimpanzee communities at Gombe National Park, Tanzania. As expected, given that females commonly outrank males, we found that bonobos exhibited lower rates of male-female aggression and higher rates of female-male aggression than chimpanzees. Surprisingly, we found higher rates of male-male aggression among bonobos than chimpanzees even when limiting analyses to contact aggression. In both species, more aggressive males obtained higher mating success. Although our findings indicate that the frequency of male-male aggression does not parallel species difference in its intensity, they support the view that contrary to male chimpanzees, whose reproductive success depends on strong coalitions, male bonobos have more individualistic reproductive strategies.25.

The variation and evolution of complete human centromeres.

Human centromeres have been traditionally very difficult to sequence and assemble owing to their repetitive nature and large size1. As a result, patterns of human centromeric variation and models for their evolution and function remain incomplete, despite centromeres being among the most rapidly mutating regions2,3. Here, using long-read sequencing, we completely sequenced and assembled all centromeres from a second human genome and compared it to the finished reference genome4,5. We find that the two sets of centromeres show at least a 4.1-fold increase in single-nucleotide variation when compared with their unique flanks and vary up to 3-fold in size. Moreover, we find that 45.8% of centromeric sequence cannot be reliably aligned using standard methods owing to the emergence of new α-satellite higher-order repeats (HORs). DNA methylation and CENP-A chromatin immunoprecipitation experiments show that 26% of the centromeres differ in their kinetochore position by >500 kb. To understand evolutionary change, we selected six chromosomes and sequenced and assembled 31 orthologous centromeres from the common chimpanzee, orangutan and macaque genomes. Comparative analyses reveal a nearly complete turnover of α-satellite HORs, with characteristic idiosyncratic changes in α-satellite HORs for each species. Phylogenetic reconstruction of human haplotypes supports limited to no recombination between the short (p) and long (q) arms across centromeres and reveals that novel α-satellite HORs share a monophyletic origin, providing a strategy to estimate the rate of saltatory amplification and mutation of human centromeric DNA.

Chaos and COSMOS-Considerations on QSM methods with multiple and single orientations and effects from local anisotropy.

PURPOSE: Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (COSMOS) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0°, 60° and 120° in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of ±25°. Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the COSMOS model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain. METHODS: Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 µm resolution, 10 orientations) including ideal COSMOS sampling and realistic rotations in vivo. Comparisons of the results included ideal COSMOS, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM. RESULTS: In-vivo feasible and optimal COSMOS yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. COSMOS reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts. CONCLUSION: In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal COSMOS schemes over regularized single-orientation QSM appear limited in in-vivo settings.

Conserved patterns and locomotor-related evolutionary constraints in the hominoid vertebral column.

The evolution of the hominoid lineage is characterized by pervasive homoplasy, notably in regions such as the vertebral column, which plays a central role in body support and locomotion. Few isolated and fewer associated vertebrae are known for most fossil hominoid taxa, but identified specimens indicate potentially high levels of convergence in terms of both form and number. Homoplasy thus complicates attempts to identify the anatomy of the last common ancestor of hominins and other taxa and stymies reconstructions of evolutionary scenarios. One way to clarify the role of homoplasy is by investigating constraints via phenotypic integration, which assesses covariation among traits, shapes evolutionary pathways, and itself evolves in response to selection. We assessed phenotypic integration and evolvability across the subaxial (cervical, thoracic, lumbar, sacral) vertebral column of macaques (n = 96), gibbons (n = 77), chimpanzees (n = 92), and modern humans (n = 151). We found a mid-cervical cluster that may have shifted cranially in hominoids, a persistent thoracic cluster that is most marked in chimpanzees, and an expanded lumbosacral cluster in hominoids that is most expanded in gibbons. Our results highlight the highly conserved nature of the vertebral column. Taxa appear to exploit existing patterns of integration and ontogenetic processes to shift, expand, or reduce cluster boundaries. Gibbons appear to be the most highly derived taxon in our sample, possibly in response to their highly specialized locomotion.

Modulation of cell-mediated immunity during pregnancy in wild bonobos.

During pregnancy, the mammalian immune system must simultaneously protect against pathogens while being accommodating to the foreign fetal tissues. Our current understanding of this immune modulation derives predominantly from industrialized human populations and laboratory animals. However, their environments differ considerably from the pathogen-rich, resource-scarce environments in which pregnancy and the immune system co-evolved. For a better understanding of immune modulation during pregnancy in challenging environments, we measured urinary neopterin, a biomarker of cell-mediated immune responses, in 10 wild female bonobos (Pan paniscus) before, during and after pregnancy. Bonobos, sharing evolutionary roots and pregnancy characteristics with humans, serve as an ideal model for such investigation. Despite distinct environments, we hypothesized that cell-mediated immune modulation during pregnancy is similar between bonobos and humans. As predicted, neopterin levels were higher during than outside of pregnancy, and highest in the third trimester, with a significant decline post-partum. Our findings suggest shared mechanisms of cell-mediated immune modulation during pregnancy in bonobos and humans that are robust despite distinct environmental conditions. We propose that these patterns indicate shared immunological processes during pregnancy among hominins, and possibly other primates. This finding enhances our understanding of reproductive immunology.

The Inhibitory Effect of Early Pregnancy Factor on Red Meat Neu5Gc-Mediated Antibody Production in CMAH-/- Mice.

The meat derived from mammals such as cows, sheep, and pigs is commonly referred to as red meat. Recent studies have shown that consuming red meat can activate the immune system, produce antibodies, and subsequently develop into tumors and cancer. This is due to the presence of a potential carcinogenic compound in red meat called N-ethanol neuraminic acid (Neu5Gc). Neu5Gc is a common sialic monosaccharide in mammals, synthesized from N-acetylneuraminic acid (Neu5Ac) in the body and typically present in most mammals. However, due to the lack of the CMAH gene encoding the cytidine 5'-monophosphate Neu5Ac hydroxylase, humans are unable to synthesize Neu5Gc. Compared to primates such as mice or chimpanzees, the specific loss of Neu5Gc expression in humans is attributed to fixed genome mutations in CMAH. Although Neu5Gc cannot be produced, it can be introduced from specific dietary sources such as red meat and milk, so it is necessary to use mice or chimpanzees that knock out the CMAH gene instead of humans as experimental models. Further research has shown that early pregnancy factor (EPF) has the ability to regulate CD4+T cell-dependent immune responses. In this study, we established a simulated human animal model using C57/BL6 mice with CMAH gene knockout and analyzed the inhibitory effect of EPF on red meat Neu5Gc-induced CMAH-/- C57/BL6 mouse antibody production and chronic inflammation development. The results showed that the intervention of EPF reduced slow weight gain and shortened colon length in mice. In addition, EPF treatment significantly reduced the levels of anti Neu5Gc antibodies in the body, as well as the inflammatory factors IL-6 and IL-1ß, TNF-α and the activity of MPO. In addition, it also alleviated damage to liver and intestinal tissues and reduced the content of CD4 cells and the expression of B cell activation molecules CD80 and CD86 in mice. In summary, EPF effectively inhibited Neu5Gc-induced antibody production, reduced inflammation levels in mice, and alleviated Neu5Gc-induced inflammation. This will provide a new re-search concept and potential approach for developing immunosuppressants to address safety issues related to long-term consumption of red meat.

Comprehensive characterization of ERV-K (HML-8) in the chimpanzee genome revealed less genomic activity than humans.

Endogenous retroviruses (ERVs) originate from ancestral germline infections caused by exogenous retroviruses. Throughout evolution, they have become fixed within the genome of the animals into which they were integrated. As ERV elements coevolve with the host, they are normally epigenetically silenced and can become upregulated in a series of physiological and pathological processes. Generally, a detailed ERV profile in the host genome is critical for understanding the evolutionary history and functional performance of the host genome. We previously characterized and cataloged all the ERV-K subtype HML-8 loci in the human genome; however, this has not been done for the chimpanzee, the nearest living relative of humans. In this study, we aimed to catalog and characterize the integration of HML-8 in the chimpanzee genome and compare it with the integration of HML-8 in the human genome. We analyzed the integration of HML-8 and found that HML-8 pervasively invaded the chimpanzee genome. A total of 76 proviral elements were characterized on 23/24 chromosomes, including detailed elements distribution, structure, phylogeny, integration time, and their potential to regulate adjacent genes. The incomplete structure of HML-8 proviral LTRs will undoubtedly affect their activity. Moreover, the results indicated that HML-8 integration occurred before the divergence between humans and chimpanzees. Furthermore, chimpanzees include more HML-8 proviral elements (76 vs. 40) and fewer solo long terminal repeats (LTR) (0 vs. 5) than humans. These results suggested that chimpanzee genome activity is less than the human genome and that humans may have a better ability to shape and screen integrated proviral elements. Our work is informative in both an evolutionary and a functional context for ERVs.