Mammals are metagenomic in that they are composed not only of their own gene complements but also those of all of their associated microbes. To understand the co-evolution of the mammals and their indigenous microbial communities, we conducted a network-based analysis of bacterial 16S rRNA gene sequences from the fecal microbiota of humans and 59 other mammalian species living in two zoos and the wild. The results indicate that host diet and phylogeny both influence bacterial diversity, which increases from carnivory to omnivory to herbivory, that bacterial communities codiversified with their hosts, and that the gut microbiota of humans living a modern lifestyle is typical of omnivorous primates.Our 'metagenome' is a composite of Homo sapiens genes and genes present in the genomes of the trillions of microbes that colonize our adult bodies (1). The vast majority of these microbes live in our distal guts. 'Our' microbial genomes (microbiome) encode metabolic functions that we have not had to evolve wholly on our own, including the ability to extract energy and nutrients from our diet. It is unclear how distinctively human our gut microbiota is, or how modern H. sapiens' ability to construct a wide range of diets has affected our gut microbial ecology. In this study we address two general questions concerning the evolution of mammals: how do diet and host phylogeny shape mammalian microbiota? When a mammalian species acquires a new dietary niche, how does its gut microbiota relate to the microbiota of its close relatives?The acquisition of a new diet is a fundamental driver for the evolution of new species. Coevolution, the reciprocal adaptations occurring between interacting species (2), produces dramatic physiological changes that are often recorded in fossil remains. For instance, although mammals made their first appearance on the world stage in the Jurassic (~160 Ma), most modern species arose during the Quaternary (1.8 Ma to present (5)), when C4-grasslands expanded in response to a fall in atmospheric CO 2 levels and/or climate changes (6-8). The switch to a C4 plant-dominated diet selected for herbivores with high-crowned teeth (3) and longer gut retention times necessary for the digestion of lower-quality forage (9). However, these adaptations may not suffice for the exploitation of a new dietary niche. The community

Abstract. Haemoproteus spp. are ancient apicomplexan hemoparasites that have undergone extensive coevolution with their natural hosts and are typically species specific, with inapparent or minimal pathogenicity. A promiscuous genotype of Haemoproteus capable of undergoing host switching on a familial level was identified. This protozoan caused severe disease with high mortality in 6 species of exotic passerine birds housed in California at the San Diego Zoo's Wild Animal Park: Surinam crested oropendola (Psarocolius decumanus decumanus), Guianan turquoise tanager (Tangara mexicana mexicana), blue-necked tanager (Tangara cyanicollis caeruleocephala, Guianan red-capped cardinal (Paroaria gularis gularis), magnificent bird of paradise (Diphyllodes magnificus hunsteini), and superb bird of paradise (Lophorina superba). The birds had few or no clinical signs. Necropsy findings consisted of hemocoelom and irregularly scattered areas of hemorrhage and hepatocellular necrosis. Affected areas of liver contained solitary protozoal megaloschizonts in varied states of degeneration and peripheral nonsuppurative inflammation. No other parasite life stages were found in parenchymal organs or blood smears. Polymerase chain reaction using consensus primers for an avian malarial mitochondrial cytochrome B gene segment was positive in all cases. Sequencing and BLAST analysis identified the protozoan as a Haemoproteus sp. related to Haemoproteus spp. found in asymptomatic passerine birds native to North America. In situ hybridization was performed in 3 animals with a mitochondrial cytochrome B probe and was positive only in megaloschizonts. These findings suggest the recognition of a genotype of Haemoproteus that exhibits high levels of host infidelity and causes severe disease in captive birds exotic to North America.

While prion infection of the lymphoreticular system (LRS) is necessary for neuroinvasion in many prion diseases, in bovine spongiform encephalopathy and atypical cases of sheep scrapie there is evidence to challenge that LRS infection is required for neuroinvasion. Here we investigated the role of prion infection of LRS tissues in neuroinvasion following extraneural inoculation with the HY and DY strains of the transmissible mink encephalopathy (TME) agent. DY TME agent infectivity was not detected in spleen or lymph nodes following intraperitoneal inoculation and clinical disease was not observed following inoculation into the peritoneum or lymph nodes, or after oral ingestion. In contrast, inoculation of the HY TME agent by each of these peripheral routes resulted in replication in the spleen and lymph nodes and induced clinical disease. To clarify the role of the LRS in neuroinvasion, the HY and DY TME agents were also inoculated into the tongue because it is densely innervated and lesions on the tongue, which are common in ruminants, increase the susceptibility of hamsters to experimental prion disease. Following intratongue inoculation, the DY TME agent caused prion disease and was detected in both the tongue and brainstem nuclei that innervate the tongue, but the prion protein PrP Sc was not detected in the spleen or lymph nodes. These findings indicate that the DY TME agent can spread from the tongue to the brain along cranial nerves and neuroinvasion does not require agent replication in the LRS. These studies provide support for prion neuroinvasion from highly innervated peripheral tissues in the absence of LRS infection in natural prion diseases of livestock.In scrapie infection of sheep and chronic wasting disease infection of cervids, prion agent infection and replication in the gut-associated lymphoreticular system (LRS) precede entry into the nervous system following oral prion exposure (1,15,29,35). After infection of the LRS, the prion agent enters peripheral nerves and retrogradely spreads to the central nervous system, where it can replicate to high levels. The scrapie agent also retrogradely spreads from the enteric nervous system to the dorsal motor nucleus of the vagus in the brainstem via the vagus nerve (21,28,36). These modes of neuroinvasion are postulated to be dependent on prior agent amplification in the LRS. This is supported by studies using mice that are not susceptible to prion infection via extraneural routes of inoculation as a result of a permanent or transient loss of functional germinal centers in lymphoid follicles (17)(18)(19)(20)22).However, in bovine spongiform encephalopathy (BSE)-infected cattle and atypical scrapie, the role of the LRS in prion neuroinvasion is less clear, and perhaps not essential. In natural cases of BSE, prion infectivity has not been detected in lymph nodes or spleen, and the disease-specific isoform of the prion protein PrP Sc was not found in the distal ileum (31). Following experimental oral exposure of calves to the BSE agent, BSE infectivity w...