Skip to main content
Dryad logo

MHC class II genotype-by-pathogen genotype interaction for infection prevalence in a natural rodent-Borrelia system


Råberg, Lars (2022), MHC class II genotype-by-pathogen genotype interaction for infection prevalence in a natural rodent-Borrelia system, Dryad, Dataset,


MHC genes are extraordinarily polymorphic in most taxa. Host-pathogen coevolution driven by negative frequency-dependent selection (NFDS) is one of the main hypotheses for the maintenance of such immunogenetic variation. Here we test a critical but rarely tested assumption of this hypothesis—that MHC alleles affect resistance/susceptibility to a pathogen in a strain-specific way, i.e. that there is a host genotype-by-pathogen genotype interaction. In a field study of bank voles naturally infected with the tick-transmitted bacterium Borrelia afzelii, we tested for MHC class II (DQB) genotype-by-B. afzelii strain interactions for infection prevalence between ten DQB alleles and seven strains. One allele (DQB*37) showed an interaction, such that voles carrying DQB*37 had higher prevalence of two strains and lower prevalence of one strain than individuals without the allele. These findings were corroborated by analyses of strain composition of infections, which revealed an effect of DQB*37 in the form of lower b diversity among infections in voles carrying the allele. Taken together, these results provide rare support at the molecular genetic level for a key assumption of models of antagonistic coevolution through NFDS.


Field sampling

Animals for this study were trapped at Kalvs mosse, a damp deciduous wood (ca 24 ha) at Revingehed in southern Sweden (55°42’N, 13°29’E), in May-October 2006-2014. Animals were trapped with live traps (Ugglan special, GrahnAB, Sweden) baited with grains and apple or carrot. From each individual we took a skin biopsy (Ø 2 mm) from the ear for DNA extraction. We also recorded body mass to the nearest 0.1 g using a Pesola spring balance. During 2007-2008, we collected longitudinal data by trapping bank voles about every 6 weeks during May-October and tagging each individual with a transponder (Trovan ID-100 Unique) subcutaneously implanted on the back, which allowed identification of each individual upon recapture.

DQB and ospC sequencing

Skin biopsies were stored in 70% ethanol until DNA extraction using the protocol of (Laird et al. 1991).

B. afzelii-infected bank voles were identified by real-time PCR of flaB (Råberg 2012). To determine which ospC strains an infected vole carried we used 454 amplicon pyrosequencing, as described in Strandh and Råberg (2015). The ospC data set used in the present study is the same as in Råberg et al. (2017).

B. afzelii-infected voles were genotyped at DQB by amplifying 205 out of 272bp in exon 2 using the primers MyglDQBfw and MyglDQBrv (Scherman et al. 2014), followed by amplicon sequencing. Exon 2 contains the majority of the peptide binding residues and is the most polymorphic exon in this gene (Scherman et al. 2014). Two different sequencing methods were used: 300 bp paired-end Illumina MiSeq sequencing (N=265 in the final data set) and 454 pyrosequencing (N=36 in the final data set; a subset of the data from Scherman et al. (2021). Libraries were prepared and the data filtered as described in Scherman et al. (2021). The concordance between Illumina MiSeq sequencing and 454 pyrosequencing of MHC is high (Razali et al. 2017). The reproducibility (number of DQB alleles detected in all replicates from an individual/total number of DQB alleles detected in that individual) was in all cases 100% for both Illumina MiSeq sequencing (samples from 34 longitudinally sampled voles; 2-4 samples/vole) and 454 pyrosequencing (13 technical duplicates; Scherman et al. 2021).

Laird, P., Zijderveld, A., Linders, K. & Rudnicki, M. (1991). Simplified mammalian DNA isolation procedure. Nucleic Acids Res., 19, 4293.

Råberg, L. (2012). Infection intensity and infectivity of the tick-borne pathogen Borrelia afzelii. J. Evol. Biol., 25.

Råberg, L., Hagström, Å., Andersson, M., Bartkova, S., Scherman, K., Strandh, M., et al. (2017). Evolution of antigenic diversity in the tick-transmitted bacterium Borrelia afzelii: a role for host specialization? J. Evol. Biol., 30, 1034–1041.

Razali, H., O’Connor, E., Drews, A., Burke, T. & Westerdahl, H. (2017). A quantitative and qualitative comparison of illumina MiSeq and 454 amplicon sequencing for genotyping the highly polymorphic major histocompatibility complex (MHC) in a non-model species. BMC Res. Notes, 10, 346.

Scherman, K., Råberg, L. & Westerdahl, H. (2014). Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus). J. Mol. Evol., 78.

Scherman, K., Råberg, L. & Westerdahl, H. (2021). Borrelia Infection in Bank Voles Myodes glareolus Is Associated With Specific DQB Haplotypes Which Affect Allelic Divergence Within Individuals. Front. Immunol., 12, 703025.

Strandh, M. & Råberg, L. (2015). Within-host competition between Borrelia afzelii ospC strains in wild hosts as revealed by massively parallel amplicon sequencing. Philos. Trans. R. Soc. London. B, 370, 20140293.



Crafoordska Stiftelsen