Ecology of Ixodes pacificus Ticks and Associated Pathogens in the Western United States

Lyme disease is the most important vector-borne disease in the United States and is increasing in incidence and geographic range. In the Pacific west, the western black-legged tick, Ixodes pacificus Cooley and Kohls, 1943 is an important vector of the causative agent of Lyme disease, the spirochete, Borrelia burgdorferi. Ixodes pacificus life cycle is expected to be more than a year long, and all three stages (larva, nymph, and adult) overlap in spring. The optimal habitat consists of forest cover, cooler temperatures, and annual precipitation in the range of 200–500 mm. Therefore, the coastal areas of California, Oregon, and Washington are well suited for these ticks. Immature stages commonly parasitize Western fence lizards (Sceloporus occidentalis) and gray squirrels (Sciurus griseus), while adults often feed on deer mice (Peromyscus maniculatus) and black-tailed deer (Odocoileus h. columbianus). Ixodes pacificus carry several pathogens of human significance, such as Borrelia burgdorferi, Bartonella, and Rickettsiales. These pathogens are maintained in the environment by many hosts, including small mammals, birds, livestock, and domestic animals. Although a great deal of work has been carried out on Ixodes ticks and the pathogens they transmit, understanding I. pacificus ecology outside California still lags. Additionally, the dynamic vector–host–pathogen system means that new factors will continue to arise and shift the epidemiological patterns within specific areas. Here, we review the ecology of I. pacificus and the pathogens this tick is known to carry to identify gaps in our knowledge.

Exposure to binge ethanol and fatty acid ethyl esters exacerbates chronic ethanol-induced pancreatic injury in hepatic alcohol dehydrogenase deficient deer mice

Alcoholic chronic pancreatitis (ACP) is a fibroinflammatory disease of the pancreas. However, metabolic basis of ACP is not clearly understood. In this study, we evaluated differential pancreatic injury in hepatic alcohol dehydrogenase deficient (ADH-) deer mice fed chronic ethanol (EtOH), chronic plus binge EtOH, and chronic plus binge EtOH and fatty acid ethyl esters (FAEEs, nonoxidative metabolites of EtOH) to understand the metabolic basis of ACP. Hepatic ADH- and ADH normal (ADH+) deer mice were fed Lieber-DeCarli liquid diet containing 3% (w/v) EtOH for three months. One week before the euthanization, chronic EtOH fed mice were further administered with an oral gavage of binge EtOH with/without FAEEs. Blood alcohol concentration (BAC), pancreatic injury and inflammatory markers were measured. Pancreatic morphology, ultrastructural changes, endoplasmic reticulum (ER)/oxidative stress were examined using H & E staining, electron microscopy, immunostaining, and/or Western blot, respectively. Overall, BAC was substantially increased in chronic EtOH fed groups of ADH- vs. ADH+ deer mice. A significant change in pancreatic acinar cell morphology, with mild to moderate fibrosis and ultrastructural changes evident by dilatations and disruption of ER cisternae, ER/oxidative stress along with increased levels of inflammatory markers were observed in the pancreas of chronic EtOH fed groups of ADH- vs. ADH+ deer mice. Furthermore, chronic plus binge EtOH and FAEEs exposure elevated BAC, enhanced ER/oxidative stress and exacerbated chronic EtOH-induced pancreatic injury in ADH- deer mice suggesting a role of increased body burden of EtOH and its metabolism under reduced hepatic ADH in initiation and progression of ACP.

Adaptive tail-length evolution in deer mice is associated with differential Hoxd13 expression in early development

Variation in the size and number of axial segments underlies much of the diversity in animal body plans. Here, we investigate the evolutionary, genetic, and developmental mechanisms driving tail-length differences between forest and prairie ecotypes of deer mice (Peromyscus maniculatus). We first show that long-tailed forest mice perform better in an arboreal locomotion assay, consistent with tails being important for balance during climbing. The long tails of these forest mice consist of both longer and more caudal vertebrae than prairie mice. Using quantitative genetics, we identify six genomic regions that contribute to differences in total tail length, three of which associate with vertebra length and the other three with vertebra number. For all six loci, the forest allele increases tail length, consistent with the cumulative effect of natural selection. Two of the genomic regions associated with variation in vertebra number contain Hox gene clusters. Of those, we find an allele-specific decrease in Hoxd13 expression in the embryonic tail bud of long-tailed forest mice, consistent with its role in axial elongation. Additionally, we find that forest embryos have more presomitic mesoderm than prairie embryos, and that this correlates with an increase in the number of neuromesodermal progenitors (NMPs), which are modulated by Hox13 paralogs. Together, these results suggest a role for Hoxd13 in the development of natural variation in adaptive morphology on a microevolutionary timescale.

Genetic variation in haemoglobin is associated with evolved changes in breathing in high-altitude deer mice

Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated whether genetic variants in haemoglobin (Hb) that contribute to high-altitude adaptation in deer mice (Peromyscus maniculatus) are associated with evolved changes in control of breathing. We created F2 inter-population hybrids of highland and lowland deer mice to test for phenotypic associations of α- and β-globin variants on a mixed genetic background. Hb genotype had expected effects on Hb-O2 affinity that were associated with differences in arterial O2 saturation in hypoxia. However, high-altitude genotypes were also associated with breathing phenotypes that should contribute to enhancing O2 uptake in hypoxia. Mice with highland α-globin exhibited a more effective breathing pattern, with highland homozygotes breathing deeper but less frequently across a range of inspired O2, and this difference was comparable to the evolved changes in breathing pattern in deer mouse populations native to high altitude. The ventilatory response to hypoxia was augmented in mice that were homozygous for highland β-globin. The association of globin variants with variation in breathing phenotypes could not be recapitulated by acute manipulations of Hb-O2 affinity, because treatment with efaproxiral (a synthetic drug that acutely reduces Hb-O2 affinity) had no effect on breathing in normoxia or hypoxia. Therefore, adaptive variation in haemoglobin may have unexpected effects on physiology in addition to the canonical function of this protein in circulatory O2 transport.

Investigating the effect of habitat modification on chronic stress in deer mice: a preliminary study

Anthropogenic habitat modification can lead to chronic stress in wildlife. This can result in immunosuppression and higher disease prevalence. Chronically stressed individuals typically have elevated baseline GCs and decreased body condition. GCs are called FGMs when excreted in feces and can be used to noninvasively evaluate stress in free-ranging wildlife. In the deer mouse (Peromyscus maniculatus)–SNV system, SNV prevalence is higher in deer mice at peridomestic settings, which are human-modified habitats. This is problematic because SNV causes a fatal disease in humans, and thus the higher SNV prevalence may lead to higher risk of infection for humans. In our study, we hypothesized that SNV prevalence would be higher in deer mice at human-modified habitats due to chronic stress. To test our hypothesis, we compared two stress measures (i.e., baseline FGMs and body condition scores) in deer mice from one peridomestic and one sylvan grid over 2 months. Captured deer mice were tagged, weighed, sexed and sampled for feces and blood and were evaluated for reproductive status and body condition before release. Blood samples were analysed for SNV antibodies, and fecal samples were evaluated for FGMs. We found higher deer mouse numbers at the sylvan grid. There were no differences in baseline FGM levels between peridomestic and sylvan populations. However, peridomestic deer mice had overall lower body condition. Given the low SNV prevalence across both grids, we were unable to examine potential correlations between SNV prevalence and chronic stress. Regardless, we conclude that deer mice at human-modified habitats may not be chronically stressed, which may suggest that higher SNV prevalence at peridomestic settings may not be the result of chronic stress. Although we did find that peridomestic deer mice had lower body condition, this may not have been related to chronic stress because there were no differences in baseline FGMs. Longer studies with more site replication are needed to validate and expand on our findings. Our preliminary study adds to the existing body of knowledge that examines relationships between stress physiology and disease prevalence in human-modified environments.

Methylation studies in Peromyscus: aging, altitude adaptation, and monogamy

DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (Peromyscus) are long-living rodents that have emerged as an informative model to study aging, adaptation to extreme environments, and monogamous behavior. In the present study, we have undertaken an exhaustive, genome-wide analysis of DNA methylation in Peromyscus, spanning different species, stocks, sexes, tissues, and age cohorts. We describe DNA methylation-based estimators of age for different species of deer mice based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for deer mice was trained on 3 tissues (tail, liver, and brain). Two human-Peromyscus clocks accurately measure age and relative age, respectively. We present CpGs and enriched pathways that relate to different conditions such as chronological age, high altitude, and monogamous behavior. Overall, this study provides a first step towards studying the epigenetic correlates of monogamous behavior and adaptation to high altitude in Peromyscus. The human-Peromyscus epigenetic clocks are expected to provide a significant boost to the attractiveness of Peromyscus as a biological model.