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Abstract
BackgroundThe prairie vole (Microtus ochrogaster) is a premier animal model for understanding the genetic and neurological basis of social behaviors. Unlike other biomedical models, prairie voles display a rich repertoire of social behaviors including the formation of long-term pair bonds and biparental care. However, due to a lack of genomic resources for this species, studies have been limited to a handful of candidate genes. To provide a substrate for future development of genomic resources for this unique model organism, we report the construction and characterization of a bacterial artificial chromosome (BAC) library from a single male prairie vole and a prairie vole-mouse (Mus musculus) comparative cytogenetic map.ResultsWe constructed a prairie vole BAC library (CHORI-232) consisting of 194,267 recombinant clones with an average insert size of 139 kb. Hybridization-based screening of the gridded library at 19 loci established that the library has an average depth of coverage of ~10×. To obtain a small-scale sampling of the prairie vole genome, we generated 3884 BAC end-sequences totaling ~2.8 Mb. One-third of these BAC-end sequences could be mapped to unique locations in the mouse genome, thereby anchoring 1003 prairie vole BAC clones to an orthologous position in the mouse genome. Fluorescence in situ hybridization (FISH) mapping of 62 prairie vole clones with BAC-end sequences mapping to orthologous positions in the mouse genome was used to develop a first-generation genome-wide prairie vole-mouse comparative cytogenetic map. While conserved synteny was observed between this pair of rodent genomes, rearrangements between the prairie vole and mouse genomes were detected, including a minimum of five inversions and 16 inter-chromosomal rearrangements.ConclusionsThe construction of the prairie vole BAC library and the vole-mouse comparative cytogenetic map represent the first genome-wide modern genomic resources developed for this species. The BAC library will support future genomic, genetic and molecular characterization of this genome and species, and the isolation of clones of high interest to the vole research community will allow for immediate characterization of the regulatory and coding sequences of genes known to play important roles in social behaviors. In addition, these resources provide an excellent platform for future higher resolution cytogenetic mapping and full genome sequencing.
Highlights
The prairie vole (Microtus ochrogaster) is a premier animal model for understanding the genetic and neurological basis of social behaviors
To experimentally verify the clone-depth of the library and its utility for targeted physical mapping, we screened the library with n = 54 probes from 19 discrete locations in the genome corresponding to genes that have been established to be associated with social behavior in voles, or other species
For the prairie vole-rat comparison in which the orthologous positions of the mapped prairie vole bacterial artificial chromosome (BAC) clones in the rat genome were indirectly inferred via their orthologous location in the mouse genome using the UCSC Genome Browser ‘convert’ option [19], the GRIMM algorithm estimated a total of 37 rearrangements (3 inversions and 34 interchromosomal) between the prairie vole and rat
Summary
The prairie vole (Microtus ochrogaster) is a premier animal model for understanding the genetic and neurological basis of social behaviors. All members of the Microtus genus are hypothesized to be derived from a common ancestor that lived just ~2 MYA [3,4] and it has been noted that the rate of speciation required to generate 60 species in such a short time-frame are likely to have been at least 20-fold higher than expected in a typical mammalian lineage [5] Consistent with this rapid rate of speciation, vole genomes display signatures of elevated rates of evolution. Maruyama and Imai determined that Microtus had the highest rate of karyotype alterations when compared to other rodents [8] This genus is highly enriched for unusual genomic and genetic properties associated with the X chromosome (reviewed in [9]). These unusual features of the Microtus genomes make them a promising model for the study of genome evolution
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