Epigenetic Inheritance across the Landscape

The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype

Population genetic patterns among social groups of the endangered Central American spider monkey (Ateles geoffroyi) in a human-dominated landscape

Spider monkeys (Genus: Ateles) are a widespread Neotropical primate with a highly plastic socioecological strategy. However, the Central American species, Ateles geoffroyi, was recently re-listed as endangered due to the accelerated loss of forest across the subcontinent. There is inconsistent evidence that spider monkey populations could persist when actively protected, but their long-term viability in unprotected, human-dominated landscapes is not known. We analyzed noninvasive genetic samples from 185 individuals in 14 putative social groups on the Rivas Isthmus in southwestern Nicaragua. We found evidence of weak but significant genetic structure in the mitochondrial control region and in eight nuclear microsatellite loci plus negative spatial autocorrelation in Fst and kinship. The overall pattern suggests strong localized mating and at least historical female-biased dispersal, as is expected for this species. Heterozygosity was significantly lower than expected under random mating and lower than that found in other spider monkey populations, possibly reflecting a recent decline in genetic diversity and a threat from inbreeding. We conclude that despite a long history of human disturbance on this landscape, spider monkeys were until recently successful at maintaining gene flow. We consider the recent decline to be further indication of accelerated anthropogenic disturbance, but also of an opportunity to conserve native biodiversity. Spider monkeys are one of many wildlife species in Central America that is threatened by land cover change, and an apt example of how landscape-scale conservation planning could be used to ensure long-term persistence

Development of a Model of Natural Infection with \u3ci\u3eMycobacterium bovis\u3c/i\u3e in White-Tailed Deer

The objective of this study was to develop a suitable experimental model of natural Mycobacterium bovis infection in white-tailed deer (Odocoileus virginianus), describe the distribution and character of tuberculous lesions, and to examine possible routes of disease transmission. In October 1997, 10 mature female white-tailed deer were inoculated by intratonsilar instillation of 2 3 103 (low dose) or 2 3 105 (high dose) colony forming units (CFU) of M. bovis. In January 1998, deer were euthanatized, examined, and tissues were collected 84 to 87 days post inoculation. Possible routes of disease transmission were evaluated by culture of nasal, oral, tonsilar, and rectal swabs at various times during the study. Gross and microscopic lesions consistent with tuberculosis were most commonly seen in medial retropharyngeal lymph nodes and lung in both dosage groups. Other tissues containing tuberculous lesions included tonsil, trachea, liver, and kidney as well as lateral retropharyngeal, mandibular, parotid, tracheobronchial, mediastinal, hepatic, mesenteric, superficial cervical, and iliac lymph nodes. Mycobacterium bovis was isolated from tonsilar swabs from 8 of 9 deer from both dosage groups at least once 14 to 87 days after inoculation. Mycobacterium bovis was isolated from oral swabs 63 and 80 days after inoculation from one of three deer in the low dose group and none of four deer in the high dose group. Similarly, M. bovis was isolated from nasal swabs 80 and 85 days after inoculation in one of three deer from the low dose group and 63 and 80 days after inoculation from two of four deer in the high dose group. Intratonsilar inoculation with M. bovis results in lesions similar to those seen in naturally infected white-tailed deer; therefore, it represents a suitable model of natural infection. These results also indicate that M. bovis persists in tonsilar crypts for prolonged periods and can be shed in saliva and nasal secretions. These infected fluids represent a likely route of disease transmission to other animals or humans

Nitric Oxide Production as an Indication of \u3ci\u3eMycobacterium Bovis \u3c/i\u3eInfection in White-Tailed Deer (\u3ci\u3eOdocoileus virginianus\u3c/i\u3e)

White-tailed deer ( Odocoileus virginianus ) are reservoirs for Mycobacterium bovis in northeast Michigan, USA. Production of nitric oxide (NO) by activated macrophages is a potent mechanism of mycobacterial killing. The capacity of macrophages to produce NO, however, varies among mammalian species. The objective of this study was to determine if mononuclear cells from white-tailed deer produce nitrite as an indication of NO production and, if so, is NO produced in response to stimulation with M. bovis antigens. Supernatants were harvested from adherent peripheral blood mononuclear cell (PBMC) cultures that had been stimulated with either Mannheimia haemolytica lipopolysaccharide (LPS) or media alone (i.e., no stimulation). Nitrite levels within M. haemolytica LPS-stimulated culture supernatants exceeded (P \u3c 0.05) those detected within supernatants from non-stimulated cultures as well as those detected within supernatants from cultures receiving an inhibitor of NO synthase in addition to M. haemolytica LPS. In response to stimulation with M. bovis antigens, nitrite production by PBMC from M. bovis -infected deer exceeded (P \u3c 0.05) the production by PBMC from non-infected deer. The response of PBMC from infected deer to M. bovis antigens exceeded (P \u3c 0.05) the response of parallel cultures from the same deer receiving no stimulation. The response of PBMC from M. bovis -infected deer to M. avium antigens did not differ from that of PBMC from M. bovis infected deer to no stimulation or from that of PBMC from non-infected deer to M. avium antigens. These findings indicate that adherent PBMC from white-tailed deer are capable of NO production and that mononuclear cells isolated from M. bovis -infected white-tailed deer produce NO in an antigen-specific recall response

Nitric Oxide Production as an Indication of \u3ci\u3eMycobacterium Bovis \u3c/i\u3eInfection in White-Tailed Deer (\u3ci\u3eOdocoileus virginianus\u3c/i\u3e)

White-tailed deer ( Odocoileus virginianus ) are reservoirs for Mycobacterium bovis in northeast Michigan, USA. Production of nitric oxide (NO) by activated macrophages is a potent mechanism of mycobacterial killing. The capacity of macrophages to produce NO, however, varies among mammalian species. The objective of this study was to determine if mononuclear cells from white-tailed deer produce nitrite as an indication of NO production and, if so, is NO produced in response to stimulation with M. bovis antigens. Supernatants were harvested from adherent peripheral blood mononuclear cell (PBMC) cultures that had been stimulated with either Mannheimia haemolytica lipopolysaccharide (LPS) or media alone (i.e., no stimulation). Nitrite levels within M. haemolytica LPS-stimulated culture supernatants exceeded (P \u3c 0.05) those detected within supernatants from non-stimulated cultures as well as those detected within supernatants from cultures receiving an inhibitor of NO synthase in addition to M. haemolytica LPS. In response to stimulation with M. bovis antigens, nitrite production by PBMC from M. bovis -infected deer exceeded (P \u3c 0.05) the production by PBMC from non-infected deer. The response of PBMC from infected deer to M. bovis antigens exceeded (P \u3c 0.05) the response of parallel cultures from the same deer receiving no stimulation. The response of PBMC from M. bovis -infected deer to M. avium antigens did not differ from that of PBMC from M. bovis infected deer to no stimulation or from that of PBMC from non-infected deer to M. avium antigens. These findings indicate that adherent PBMC from white-tailed deer are capable of NO production and that mononuclear cells isolated from M. bovis -infected white-tailed deer produce NO in an antigen-specific recall response

Content-specific auditing of a large scale anatomy ontology

Biomedical ontologies are envisioned to be usable in a range of research and clinical applications. The requirements for such uses include formal consistency, adequacy of coverage, and possibly other domain specific constraints. In this report we describe a case study that illustrates how application specific requirements may be used to identify modeling problems as well as data entry errors in ontology building and evolution. We have begun a project to use the UW Foundational Model of Anatomy (FMA) in a clinical application in radiation therapy planning. This application focuses mainly (but not exclusively) on the representation of the lymphatic system in the FMA, in order to predict the spread of tumor cells to regional metastatic sites. This application requires that the downstream relations associated with lymphatic system components must only be to other lymphatic chains or vessels, must be at the appropriate level of granularity, and that every path through the lymphatic system must terminate at one of the two well known trunks of the lymphatic system. It is possible through a programmable query interface to the FMA to write small programs that systematically audit the FMA for compliance with these constraints. We report on the design of some of these programs, and the results we obtained by applying them to the lymphatic system. The algorithms and approach are generalizable to other network organ systems in the FMA such as arteries and veins. In addition to illustrating exact constraint checking methods, this work illustrates how the details of an application may reflect back a requirement to revise the design of the ontology itself