Trade-offs in a pathogen-rich world : genetic and maternal drivers of variation in costly resistance and immunity in African buffalo (Syncerus caffer)

Disease acts as a powerful selective force in natural systems, driving the rapid evolution of resistance in the host. In the face of a myriad of pathogenic challenges in natural systems, hosts must balance the energetic needs of maintenance and reproduction with costly resistance mechanisms. In this dissertation I will (1) characterize Mycobacterium bovis (bovine tuberculosis (bTB)) resistance strategies in African buffalo (Syncerus caffer) and determine associated costs that lead to the maintenance of variation in host response, (2) identify putative mechanisms of bTB infection resistance, and (3) determine the effects of maternal rearing environment on calf survival, growth, and immune development. Here I demonstrate measureable costs of a highly heritable form of bTB resistance in free-ranging African buffalo. Buffalo able to delay infection to a later age show reduced condition throughout life and reduced survival following infection, but a higher overall reproductive rate. Taken together, the costs and benefits of infection resistance imply a “fast” life history strategy in these animals as they reproduce early, die after infection, and show evidence of investment in highly costly immunity to prevent infection with bTB. I also present evidence that variation in infection resistance is mechanistically tied to phagocyte activation, with measurable differences in IL-12 production among genotypes at a locus associated with a four-fold increase in bTB risk. Additionally, I reveal that milk fat content is highly conserved across mothers, but immune components of milk vary in a resource-dependent manner with mothers of higher condition, size, and age provisioning higher concentrations of immune-active constituents. However, although milk fat positively impacts calf survival, associations of immune components are less clear. Generally, lactoferrin (an anti-microbial peptide) and immunoglobulin G (IgG) in milk associated with higher growth rates, but lower immune function in the calf, especially before weaning. These findings agree with theoretical predictions that maternal passive immunity acts to ‘free-up’ neonatal energetic resources for growth. Taken together, this body of work elucidates the roles of genetic background and maternal effects on disease susceptibility and early health and immunity and represents a unique validation of previously proposed theoretical and laboratory work. Additionally, patterns in disease response and maternal provisioning identified here contribute to our overall understanding of resource partitioning in stochastic systems.Keywords: evolutionary ecology, host-parasite, ecoimmunolog

Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host

Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as “infection resistance,” in which hosts delay or prevent infection, and “proliferation resistance,” in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2 = 0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection-resistant animals thus appear to follow a “fast” pace-of-life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health—such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population

The heterogeneous herd : drivers of close‐contact variation in African buffalo and implications for pathogen invasion

Many infectious pathogens are shared through social interactions, and examining host connectivity has offered valuable insights for understanding patterns of pathogen transmission across wildlife species. African buffalo are social ungulates and important reservoirs of directly‐transmitted pathogens that impact numerous wildlife and livestock species. Here, we analyzed African buffalo social networks to quantify variation in close contacts, examined drivers of contact heterogeneity, and investigated how the observed contact patterns affect pathogen invasion likelihoods for a wild social ungulate. We collected continuous association data using proximity collars and sampled host traits approximately every 2 months during a 15‐month study period in Kruger National Park, South Africa. Although the observed herd was well connected, with most individuals contacting each other during each bimonthly interval, our analyses revealed striking heterogeneity in close‐contact associations among herd members. Network analysis showed that individual connectivity was stable over time and that individual age, sex, reproductive status, and pairwise genetic relatedness were important predictors of buffalo connectivity. Calves were the most connected members of the herd, and adult males were the least connected. These findings highlight the role susceptible calves may play in the transmission of pathogens within the herd. We also demonstrate that, at time scales relevant to infectious pathogens found in nature, the observed level of connectivity affects pathogen invasion likelihoods for a wide range of infectious periods and transmissibilities. Ultimately, our study identifies key predictors of social connectivity in a social ungulate and illustrates how contact heterogeneity, even within a highly connected herd, can shape pathogen invasion likelihoods

Framing the discussion of microorganisms as a facet of social equity in human health

What do “microbes” have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the “health” of the environments we build. The loss, gain, and retention of microorganisms—their flow between humans and the environment—can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure

Shell length of Dreissena polymorpha relative to substrate position.

In the past 8 years since their discovery in Lake St. Clair, the invasive species Dreissena polymorpha has spread steadily throughout Lake Huron, Michigan, Superior, and many inland lakes in Michigan (Shankland et al., 2005). Understanding this species life cycle, morphology, and most of all behavior is essential in obtaining the goal of one day removing these foreign invaders from the Michigan lake system. Through understanding such behavioral criteria as how Dreissena colonizes an area, there is potential to illuminate the answers to the problems they pose in lake ecosystems. A post-veliger Dreissena larvae will attach to a substrate once it becomes too heavy to maintain a planktonic existence, and will, after colonization, compete for an ideal substrate position. In colonization on a cylindrical substrate such as a branch or log, the mean shell length of Dreissena increases as they are situated down the vertical axis of a substrate (p=6.29 E-58). Through the data analysis of field measurements of arc length and angle position, it is apparent that this relationship exists on cylindrical substrates. It was found that this relationship to substrate position is a consequence of mass (p=2.64, E-44) and length (p=6.29. E-58) distributions through intra-specific competition for ideal substrate space. Dreissena is ideally approaching the lower horizontal plane of a substrate, which, through the work presented here, was found to be its ideal habitat in terns of fitness. The results of this experiment apply to all lake ecosystems and are therefore critical in understanding some aspects of Dreissena behavior.http://deepblue.lib.umich.edu/bitstream/2027.42/55123/1/3568.pdfDescription of 3568.pdf : Access restricted to on-site users at the U-M Biological Station

Parasites in Yellow Perch (Perca flavescens) and Rock Bass (Ambloplites rupestris) in Northern Michigan: A comparative study of the time periods 1940-1942 and 2006.

In 1940 at the University of Michigan Biological Station, located on the southern shore of South Fishtail Bay on Douglas Lake in Pellston, Michigan, records began to be compiled in reference to host cards completed for dissected specimens. A variety of parasitic organisms were included in these records, ranging from helminthes to protozoans to parasitic arthropods. The following study, conducted by Aaron Tavalire with research partner Bryan J. Cohen, compares the prevalence of parasite species recorded in the 1940-1942 time period to a collection of data sets and specimens gathered in the summer of 2006, during a three week period beginning July 15th and ending August 7th. Parasites observed in Perca flavenscens (yellow perch) were found to be significant in length (p0.05). Parasites of Ambloploites rupestris were not found to be significant for length, mass, life stage, or host sex (p>0.05). In present day samples, there was a larger abundance of parasitic organisms present in P. flavescens than that of A. rupestris (p<0.001), due to the presence of Diplostomum flexicaudum in a metacercarial stage in the eyes of the fish. Specimens from 1940-1942 showed a higher prevalence of cestodes and acanthocephalans, and the 2006 data set showed a higher prevalence of trematodes than the records of 1940-42. An equal number (1) of nematodes were present in each data set.http://deepblue.lib.umich.edu/bitstream/2027.42/55122/1/3567.pdfDescription of 3567.pdf : Access restricted to on-site users at the U-M Biological Station

Tavalire_et_al_ProcB_S.caffer_unfiltered_SNPs_n=160_Final

This file contains unfiltered SNPs obtained by 2bRAD genomic sequencing methods. Each row contains one SNP with marker metadata in the first five columns, followed by animal genotypes in subsequent columns

History of breastfeeding but not mode of delivery shapes the gut microbiome in childhood.

BackgroundThe naïve neonatal gut is sensitive to early life experiences. Events during this critical developmental window may have life-long impacts on the gut microbiota. Two experiences that have been associated with variation in the gut microbiome in infancy are mode of delivery and feeding practices (eg, breastfeeding). It remains unclear whether these early experiences are responsible for microbial differences beyond toddlerhood.AimsOur study examined whether mode of delivery and infant feeding practices are associated with differences in the child and adolescent microbiome.Design, subjects, measuresWe used an adoption-sibling design to compare genetically related siblings who were reared together or apart. Gut microbiome samples were collected from 73 children (M = 11 years, SD = 3 years, range = 3-18 years). Parents reported on child breastfeeding history, age, sex, height, and weight. Mode of delivery was collected through medical records and phone interviews.ResultsNegative binomial mixed effects models were used to identify whether mode of delivery and feeding practices were related to differences in phylum and genus-level abundance of bacteria found in the gut of child participants. Covariates included age, sex, and body mass index. Genetic relatedness and rearing environment were accounted for as random effects. We observed a significant association between lack of breastfeeding during infancy and a greater number of the genus Bacteroides in stool in childhood and adolescence.ConclusionThe absence of breastfeeding may impart lasting effects on the gut microbiome well into childhood

Tavalire_et_al_ProcB_cytokines_and_covariates_n=160_Final

This file contains the phenotypic data used in Tavalire et al. 2019 for the time to onset of bTB GWAS analysis, final time-to-event multi-locus genotype models, and longitudinal cytokine production models. Each row corresponds to a single capture time point for an animal identified by a unique Animal.ID, followed by month, year, and season of capture and demographic and phenotypic information. Some variables (e.g., bTB status) are repeated across all captures for each animal and can be extracted for single-observation analyses (e.g., time to onset of bTB GWAS analysis). All animals are female

Host genomic variation shapes gut microbiome diversity in threespine stickleback fish

ABSTRACT Variation among host-associated microbiomes is well documented across species, populations, and individuals. While numerous factors can contribute to this variation, understanding the influence of host genetic differences on microbial variation is particularly important for predicting co-evolutionary dynamics between hosts and their microbiota. Functional understanding of host genetic and microbial covariation is also of biomedical relevance, for example, providing insights into why some humans are more susceptible to chronic disorders like inflammatory bowel diseases. Unfortunately, disentangling the relative contribution to microbiome variation of host genetics from the environment has been difficult, particularly in humans where confounding environmental effects cannot be completely controlled experimentally. While isogenic laboratory models can be used in controlled environments, the effects on microbiomes of induced large-effect mutations may not recapitulate those of genetic variation observed in nature. Few studies have tested for the direct influence of natural host genetic variation on microbiome differences within a highly controlled environment in which hosts interact freely. To fill this gap, we performed a common garden experiment using families of genetically divergent populations of threespine stickleback fish—an outbred model organism commonly used for determining the genetic basis of complex traits in the context of natural genetic variation. Using germ-free derivation of divergent lines and hybrids between them in this experimental framework, we detected a clear, positive association between stickleback genetic dissimilarity and microbiome dissimilarity. With RAD-seq data, we identified regions of the genome that contributed most significantly to this relationship, providing insight into the genomic architecture of gut microbiome variation. IMPORTANCE A major focus of host-microbe research is to understand how genetic differences, of various magnitudes, among hosts translate to differences in their microbiomes. This has been challenging for animal hosts, including humans, because it is difficult to control environmental variables tightly enough to isolate direct genetic effects on the microbiome. Our work in stickleback fish is a significant contribution because our experimental approach allowed strict control over environmental factors, including standardization of the microbiome from the earliest stage of development and unrestricted co-housing of fish in a truly common environment. Furthermore, we measured host genetic variation over 2,000 regions of the stickleback genome, comparing this information and microbiome composition data among fish from very similar and very different genetic backgrounds. Our findings highlight how differences in the host genome influence microbiome diversity and make a case for future manipulative microbiome experiments that use host systems with naturally occurring genetic variation