To perform a genome-wide scan for loci under balancing selection in the bank vole. In particular, we are interested in finding balanced polymorphisms at loci involved in resistance to pathogens (immune genes).
Balancing selection refers to natural selection that maintains genetic variation (as opposed to positive or negative selection, which eliminate variation). It would be interesting to identify which loci are under balancing selection, because these loci should be an important source of heritable genetic variation in phenotypic traits. Haldane proposed already in 1949 that one potentially important cause of balancing selection is natural selection mediated by pathogens. If so, one would expect genes involved in resistance to pathogens (immune genes) to be over-represented among loci under balancing selection.
During the last decade, a number genome-wide scans of selection have been performed. Most of these have focused on positive selection in humans. There are also a few analyses of balancing selection in humans (Andrés et al., 2009; DeGiorgio et al, 2014). These have indeed indicated that immune genes are overrepresented as targets of balancing selection, supporting Haldane’s hypothesis. However, there is as yet very little information available from other animals; hence, it is still difficult to draw any general conclusions regarding the role of host-pathogen interactions as causes of balancing selection.
In this project we will re-sequence a set of bank voles (Myodes glareolus) and perform a genome-wide scan for targets of balancing selection, to test if immune genes are over-represented among loci under balancing selection.
We will use the bank vole (Myodes glareolus) as our study species. The bank vole is widely distributed in Europe and is a popular study species for various ecological and evolutionary questions. Råberg’s group has been using the bank vole as study species for research on the evolutionary ecology of host-pathogen interactions since 2006. This research has been continuously funded by VR. There is a bank vole genome (http://www.ncbi.nlm.nih.gov/bioproject/PRJNA290429) but it is of low quality.
Genome: The genome of one individual bank vole will be sequenced at ca 80×. DNA extracted from spleen using Qiagen’s DNeasy kit.
Annotation: Based on transcriptomes from ten tissues (brain, gonads, skin, heart, lung, liver, spleen, pancreas, intestine and kidney).
Resequencing: 30 individuals from our study population at Revingehed (samples taken from 10 subpopulations spread out over ca 100 km2) will be sequenced at ca 30× using Illumina HiSeq X. DNA extracted from spleen.
Data will be analysed with methods developed by DeGiorgio et al (2014; which identifies ancient balancing selection) and Voight et al (2006; see also Gautier & Vitalis, 2012; which identifies recent balancing selection, and/or recent positive seletion, i.e. incomplete sweeps). For the latter, data need to be phased. Both analyses also require one or more outgroups to identify derived alleles; for this the prairie vole Microtus ochrogaster and field vole M. agrestis (and perhaps Mus) can be used.