Lawrence Mugisha

The bonobo genome compared with the chimpanzee and human genomes

Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.

Age of the Association between Helicobacter pylori and Man

When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya.

Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions

ABSTRACT Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs). In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene. A plethora of novel AdV sequences were identified, representing at least 45 distinct AdVs. From the AdV-positive individuals, 29 nearly complete hexon genes were amplified and, based on phylogenetic analysis, tentatively allocated to all known human AdV species (Human adenovirus A to Human adenovirus G [HAdV-A to -G]) as well as to the only simian AdV species (Simian adenovirus A [SAdV-A]). Interestingly, five of the AdVs detected in great apes grouped into the HAdV-A, HAdV-D, HAdV-F, or SAdV-A clade. Furthermore, we report the first detection of AdVs in New World monkeys, clustering at the base of the primate AdV evolutionary tree. Most notably, six chimpanzee AdVs of species HAdV-A to HAdV-F revealed a remarkably close relationship to human AdVs, possibly indicating recent interspecies transmission events.

Bonobos fall within the genomic variation of chimpanzees

To gain insight into the patterns of genetic variation and evolutionary relationships within and between bonobos and chimpanzees, we sequenced 150,000 base pairs of nuclear DNA divided among 15 autosomal regions as well as the complete mitochondrial genomes from 20 bonobos and 58 chimpanzees. Except for western chimpanzees, we found poor genetic separation of chimpanzees based on sample locality. In contrast, bonobos consistently cluster together but fall as a group within the variation of chimpanzees for many of the regions. Thus, while chimpanzees retain genomic variation that predates bonobo-chimpanzee speciation, extensive lineage sorting has occurred within bonobos such that much of their genome traces its ancestry back to a single common ancestor that postdates their origin as a group separate from chimpanzees.

Drug-Resistant Human Staphylococcus Aureus in Sanctuary Apes Pose a Threat to Endangered Wild Ape Populations

Reintroduction of sanctuary apes to natural habitat is considered an important tool for conservation; however, reintroduction has the potential to endanger resident wild apes through the introduction of human pathogens. We found a high prevalence of drug‐resistant, human‐associated lineages of Staphylococcus aureus in sanctuary chimpanzees (Pan troglodytes) from Zambia and Uganda. This pathogen is associated with skin and soft tissue diseases and severe invasive infections (i.e. pneumonia and septicemia). Colonization by this bacterium is difficult to clear due to frequent recolonization. In addition to its pathogenic potential, human‐related S. aureus can serve as an indicator organism for the transmission of other potential pathogens like pneumococci or mycobacteria. Plans to reintroduce sanctuary apes should be reevaluated in light of the high risk of introducing human‐adapted S. aureus into wild ape populations where treatment is impossible. Am. J. Primatol. 74:1071‐1075, 2012.

Comparison of the Distal Gut Microbiota from People and Animals in Africa

The gut microbiota plays a key role in the maintenance of healthy gut function as well as many other aspects of health. High-throughput sequence analyses have revealed the composition of the gut microbiota, showing that there is a core signature to the human gut microbiota, as well as variation in its composition between people. The gut microbiota of animals is also being investigated. We are interested in the relationship between bacterial taxa of the human gut microbiota and those in the gut microbiota of domestic and semi-wild animals. While it is clear that some human gut bacterial pathogens come from animals (showing that human – animal transmission occurs), the extent to which the usually non-pathogenic commensal taxa are shared between humans and animals has not been explored. To investigate this we compared the distal gut microbiota of humans, cattle and semi-captive chimpanzees in communities that are geographically sympatric in Uganda. The gut microbiotas of these three host species could be distinguished by the different proportions of bacterial taxa present. We defined multiple operational taxonomic units (OTUs) by sequence similarity and found evidence that some OTUs were common between human, cattle and chimpanzees, with the largest number of shared OTUs occurring between chimpanzees and humans, as might be expected with their close physiological similarity. These results show the potential for the sharing of usually commensal bacterial taxa between humans and other animals. This suggests that further investigation of this phenomenon is needed to fully understand how it drives the composition of human and animal gut microbiotas.

Serosurvey of Dogs for Human, Livestock, and Wildlife Pathogens, Uganda

To the Editor: Domestic dogs live in close association with humans and livestock, participating in the transmission of diseases of zoonotic, veterinary, and conservation interest (1,2). Most households in Uganda have traditionally kept dogs for hunting and for help with herding, security, and guarding livestock. Most dogs receive no prophylactic measures (e.g., vaccinations) and roam freely; this situation exposes them to pathogens from eating garbage, rodents, and stillborn animals and other carcasses and through inhalation during scent communication. Thus, dogs are a reservoir for certain pathogens and a useful sentinel for others (3). In 2011, serum samples were obtained from 116 mixed-breed dogs during a rabies vaccination campaign in and near 3 national parks in southwestern Uganda; the dogs were >4 months of age and were voluntarily brought in by their owners (Figure, Appendix, Table). Two of the parks, Bwindi Impenetrable (BI) and Mgahinga Gorilla (MG), have some of the most biologically diverse tropical forests in eastern Africa and are home to mountain gorillas. The third park, Queen Elizabeth (QE), is home to populations of protected carnivores and ungulates. The parks lie within a densely populated rural landscape; in some areas, the population is as high as 500 persons/km2. Figure Map of Uganda showing 3 areas where a serosurvery for human and animal pathogens was conducted among dogs. 1, Queen Elizabeth National Park; 2, Bwindi Impenetrable National Park; 3, Mgahinga Gorilla National Park. Table Methodology and seroprevalence for selected pathogens in rural dogs in 3 national parks, Uganda, 2011* Of the 116 sampled dogs, 4 had been vaccinated against rabies by the authors in 2010 in QE (not included in rabies results), and 11 (all males) had been castrated by local animal healers before serum samples were obtained. The samples were used to test for seroprevalence rates to rabies virus (RABV), canine distemper virus (CDV), canine parvovirus (CPV), Leptospira interrogans, Leishmania sp., Toxoplasma gondii, and Neospora caninum (Table). Seroprevalence rates ranged from 20% to 100% (Table). CPV seroprevalence was higher in BI and QE than in MG (χ2 >12.6, p<0.001); T. gondii seroprevalence was higher in BI than in MG (Fisher p = 0.002); and RABV seroprevalence was higher in castrated than noncastrated dogs (50% vs. 10%; Fisher p = 0.005). For humans, the domestic dog is the main source of exposure to RABV. The possibility that the presence of the rabies titers in the dog serum samples was due to a previous vaccination can be ruled out because the only previous recent campaign in the area was conducted by the authors. Antibodies against RABV in apparently healthy dogs have been reported in Africa (6), and rabies seems to be not invariably fatal in dogs. Dogs that have recovered from a rabies infection are prone to shed RABV in their saliva for long periods (7). Antibodies against RABV were more frequently found in castrated dogs. This finding may be due to an increase in virus-related deaths among noncastrated dogs; such dogs tend to be more aggressive and to roam, so they may come more frequently into contact with pathogenic RABV strains. Results indicate that both CDV and CPV are actively circulating in the studied dog populations. High CDV seroprevalence rates have been reported among other rural dog populations in Africa (8). Sick, debilitated pups are at high risk for predation by wild carnivores, so spillover may take place. A dog population exhibiting similar characteristics to the population we studied was believed to be the origin of the 1994 CDV epidemic among Serengeti wildlife (8). Furthermore, carnivores use feces for scent communication, so the probability of infection by CPV in wild carnivores in the study area may also be high. In developing countries, leptospirosis is emerging as a major public health problem and also causes enormous economic losses because of disease in livestock (9). The most commonly detected serovars in this study were those that have rats and dogs as reservoirs (Table​(Table).). Visceral leishmaniasis in humans is also a major health problem in several areas of eastern Africa, where the number of cases has dramatically increased during the past 20 years. Transmission of Leishmania donovani in eastern Africa may take place through anthroponotic or zoonotic cycles, although, to our knowledge, no reservoir host had been identified (10). The mean T. gondii seroprevalence detected during this survey appears to be the highest reported for dogs worldwide. This protozoon has implications for human and animal health, and dogs, who probably become infected with T. gondii when eating raw meat, are a good sentinel for environmental contamination by this parasite. On the other hand, dogs serve as the definitive host for N. caninum, which is a major cause of abortions in cattle and causes economic losses wherever it is enzootic. Some of these diseases may also have implications for the conservation of endangered mountain gorillas. Diseases such as leptospirosis, toxoplasmosis, and especially, rabies could be fatal for gorillas, and there are unpublished reports of fights between hunting dogs and gorillas. Our work should serve as a first step toward the establishment of preventive strategies for improvements in the health of humans and domestic animals living in rural Uganda and for the health of the country’s unique wildlife. Tracing the role of dogs in the cycle of the studied pathogens is crucial for the design of control programs.

Novel cytomegaloviruses in free-ranging and captive great apes: phylogenetic evidence for bidirectional horizontal transmission

Wild great apes often suffer from diseases of unknown aetiology. This is among the causes of population declines. Because human cytomegalovirus (HCMV) is an important pathogen, especially in immunocompromised individuals, a search for cytomegaloviruses (CMVs) in deceased wild and captive chimpanzees, gorillas and orang-utans was performed. By using a degenerate PCR targeting four conserved genes (UL54-UL57), several distinct, previously unrecognized CMVs were found for each species. Sequences of up to 9 kb were determined for ten novel CMVs, located in the UL54-UL57 block. A phylogenetic tree was inferred for the ten novel CMVs, the previously characterized chimpanzee CMV, HCMV strains and Old World and New World monkey CMVs. The primate CMVs fell into four clades, containing New World monkey, Old World monkey, orang-utan and human CMVs, respectively, plus two clades that each contained both chimpanzee and gorilla isolates (termed CG1 and CG2). The tree loci of the first four clades mirrored those for their respective hosts in the primate tree, suggesting that these CMV lineages arose through cospeciation with host lineages. The CG1 and CG2 loci corresponded to those of the gorilla and chimpanzee hosts, respectively. This was interpreted as indicating that CG1 and CG2 represented CMV lineages that had arisen cospeciationally with the gorilla and chimpanzee lineages, respectively, with subsequent transfer within each clade between the host genera. Divergence dates were estimated and found to be consistent with overall cospeciational development of major primate CMV lineages. However, CMV transmission between chimpanzees and gorillas in both directions has also occurred.

Zoonotic schistosomiasis in non-human primates: past, present and future activities at the human-wildlife interface in Africa.

Schistosomiasis is one of the worlds most widely distributed and prevalent parasitic diseases. Less widely recognized is that some species of Schistosoma, including several that commonly affect humans, also cause disease in other mammalian species; in particular, infections in non-human primates are known. With interest increasing in emerging zoonotic diseases, the status of schistosomiasis as a zoonotic infection is in need of re-appraisal, especially in light of advances in application of molecular screening and epidemiological tools where newly reported infections raise general animal welfare and conservation concerns. Focusing on Africa, this review provides a summary of the occurrence of schistosomiasis in non-human primates and discusses new ways in which surveillance for schistosomiasis should be integrated into more effective conservation management and disease control strategies. Emphasis is on the more common forms of human schistosomiasis, their clinical manifestations and epidemiological significance in terms of infection reservoir potential.

Rates of genomic divergence in humans, chimpanzees and their lice

The rate of DNA mutation and divergence is highly variable across the tree of life. However, the reasons underlying this variation are not well understood. Comparing the rates of genetic changes between hosts and parasite lineages that diverged at the same time is one way to begin to understand differences in genetic mutation and substitution rates. Such studies have indicated that the rate of genetic divergence in parasites is often faster than that of their hosts when comparing single genes. However, the variation in this relative rate of molecular evolution across different genes in the genome is unknown. We compared the rate of DNA sequence divergence between humans, chimpanzees and their ectoparasitic lice for 1534 protein-coding genes across their genomes. The rate of DNA substitution in these orthologous genes was on average 14 times faster for lice than for humans and chimpanzees. In addition, these rates were positively correlated across genes. Because this correlation only occurred for substitutions that changed the amino acid, this pattern is probably produced by similar functional constraints across the same genes in humans, chimpanzees and their ectoparasites.