Microevolution of bank voles (Myodes glareolus) at neutral and immune-related genes during multiannual dynamic cycles: Consequences for Puumala hantavirus epidemiology

Abstract

Understanding how host dynamics, including variations of population size and dispersal, may affect the epidemiology of infectious diseases through ecological and evolutionary processes is an active research area. Here we focus on a bank vole (Myodes glareolus) metapopulation surveyed in Finland between 2005 and 2009. Bank vole is the reservoir of Puumala hantavirus (PUUV), the agent of nephropathia epidemica (NE, a mild form of hemorrhagic fever with renal symptom) in humans. M. glareolus populations experience multiannual density fluctuations that may influence the level of genetic diversity maintained in bank voles, PUUV prevalence and NE occurrence. We examine bank vole metapopulation genetics at presumably neutral markers and immune-related genes involved in susceptibility to PUUV (Tnf-promoter, Tlr4, Tlr7 and Mx2 gene) to investigate the links between population dynamics, microevolutionary processes and PUUV epidemiology. We show that genetic drift slightly and transiently affects neutral and adaptive genetic variability within the metapopulation. Gene flow seems to counterbalance its effects during the multiannual density fluctuations. The low abundance phase may therefore be too short to impact genetic variation in the host, and consequently viral genetic diversity. Environmental heterogeneity does not seem to affect vole gene flow, which might explain the absence of spatial structure previously detected in PUUV in this area. Besides, our results suggest the role of vole dispersal on PUUV circulation through sex-specific and density-dependent movements. We find little evidence of selection acting on immune-related genes within this metapopulation. Footprint of positive selection is detected at Tlr-4 gene in 2008 only. We observe marginally significant associations between Mx2 genotype and PUUV genogroups. These results show that neutral processes seem to be the main factors affecting the evolution of these immune-related genes at a contemporary scale, although the relative effects of neutral and adaptive forces could vary temporally with density fluctuations. Immune related gene polymorphism may in turn partly influence PUUV epidemiology in this metapopulation.

Preliminary insights into the genetics of bank vole tolerance to Puumala hantavirus in Sweden

“…Lastly, our sampling strategy consisted in the collection of samples during a single time step for each locality, although bank vole populations are known to exhibit strong multiannual density fluctuations, in particular in Fennoscandia (Henttonen, McGuire, & Hansson, ). A recent study provided evidence for temporal variations in both the direction and the efficiency of selection (Dubois, Galan, et al, ). Our results therefore need to be confirmed by analyzing temporal replicates within and between multiannual cycles of bank vole density in Sweden.…”

“…We studied the polymorphisms of immune‐related genes that have been shown to be associated with PUUV infections (Tnf promoter, Mx2 , Tlr4, and Tlr7 genes; see for a review Charbonnel et al, ). We evaluated variability at eight single nucleotide polymorphisms that have been previously identified in M. glareolus from Fennoscandia (see for details Supporting Information Table ; Guivier et al, ; Dubois, Galan, et al, ). Note that we focused on a single SNP within Tnf promoter as it had previously been shown to be involved in PUUV/ M. glareolus interaction (Guivier et al, ).…”

“…Additional studies of bank vole populations aimed at characterizing spatial differences in SNP allele frequencies or gene expression levels in candidate genes presumably repressing PUUV replication. These studies reported that tumor necrosis factor (Tnf) promoter polymorphisms and variations in Mx2 gene expression correlated with PUUV distribution in bank vole populations and NE epidemiology (Dubois, Galan, et al, 2017;Guivier et al., 2010;Guivier, Galan, Henttonen, Cosson, & Charbonnel, 2014).…”

Landscape Genetics: A Toolbox for Studying Vector-Borne Diseases

“…Landscape genetics has primarily and traditionally been used by conservation biologists, such as to identify vulnerable populations and identify areas where corridors are needed to promote gene flow (Storfer et al, 2010). More recently, landscape genetics has been used to study various infectious diseases, such as chronic wasting disease (Blanchong et al, 2008;Robinson et al, 2013), rabies in domestic dogs (Brunker et al, 2012), raccoon rabies (Rees et al, 2008(Rees et al, , 2009Cullingham et al, 2009;Côté et al, 2012), hantavirus (Guivier et al, 2011;Dubois et al, 2017), H5N1 avian influenza (Carrel et al, 2011), and malaria (Carrel et al, 2015;Lo et al, 2017a,b). This method can be useful to identifying potential hotspot areas of disease movement for targeted public health interventions and containment of disease and drug resistance.…”

Population genomics of bank vole populations reveals associations between immune related genes and the epidemiology of Puumala hantavirus in Sweden

“…The main objective of the present study was to characterize genome-wide patterns of bank vole population differentiation along a North/South transect in Sweden, and to identify specific genomic regions showing footprints of divergent selection between PUUV endemic areas in the North and non-endemic areas in the South. To that end, we used a population genomics approach relying on the sequencing of restriction-site-associated DNA (RAD-seq, see Baird et al, 2008) of pools of DNA from individuals sampled in six different localities and that have previously been characterized for a set of candidate genes (Dubois, Galan, et al, 2017). We combined different model-based methods of genome-scan, that allowed us to consider several underlying demographic scenarios, as well as putative associations with environmental variables.…”