title: Targeted capture and resequencing of 1040 genes reveal environmentally driven functional variation in grey wolves.
abstract: In an era of ever-increasing amounts of whole-genome sequence data for individuals and populations, the utility of traditional single nucleotide polymorphisms (SNPs) array-based genome scans is uncertain. We previously performed a SNP array-based genome scan to identify candidate genes under selection in six distinct grey wolf (Canis lupus) ecotypes. Using this information, we designed a targeted capture array for 1040 genes, including all exons and flanking regions, as well as 5000 1-kb nongenic neutral regions, and resequenced these regions in 107 wolves. Selection tests revealed striking patterns of variation within candidate genes relative to noncandidate regions and identified potentially functional variants related to local adaptation. We found 27% and 47% of candidate genes from the previous SNP array study had functional changes that were outliers in sweed and bayenv analyses, respectively. This result verifies the use of genomewide SNP surveys to tag genes that contain functional variants between populations. We highlight nonsynonymous variants in APOB, LIPG and USH2A that occur in functional domains of these proteins, and that demonstrate high correlation with precipitation seasonality and vegetation. We find Arctic and High Arctic wolf ecotypes have higher numbers of genes under selection, which highlight their conservation value and heightened threat due to climate change. This study demonstrates that combining genomewide genotyping arrays with large-scale resequencing and environmental data provides a powerful approach to discern candidate functional variants in natural populations.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, 610 Charles E Young Dr East, Los Angeles, CA, 90095, USA.
authors.forename: Rena M
authors.initials: RM
authors.lastname: Schweizer
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, 610 Charles E Young Dr East, Los Angeles, CA, 90095, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Center for Tropical Research, Institute of the Environment and Sustainability, University of California, 619 Charles E. Young Drive East, Los Angeles, CA, 90095, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Harrigan
authors.affiliation: CIBIO/InBio - Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661, Vairão, Portugal.|Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n., 4169-007, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Silva
authors.affiliation: Laboratory of Genetics, ISPRA (Istituto Superiore per la Protezione e Ricerca Ambientale), Via Cà Fornacetta 9, 40064, Ozzano dell'Emilia, BO, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galverni
authors.affiliation: Faculties of Environmental Design and Veterinary Medicine (Joint Appointment), EVDS, University of Calgary, 2500 University Dr NW, Calgary, Alberta, Canada, T2N 1N4.
authors.forename: Marco
authors.initials: M
authors.lastname: Musiani
authors.affiliation: Department of Biomolecular Engineering, University of California, Santa Cruz, CA, 95060, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Green
authors.affiliation: Department of Human Genetics, University of Chicago, 920 E. 58th Street, Chicago, IL, 60637, USA.
authors.forename: John
authors.initials: J
authors.lastname: Novembre
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, 610 Charles E Young Dr East, Los Angeles, CA, 90095, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Wayne
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D000818:Animals; D001110:Arctic Regions; D060146:Ecotype; D004777:Environment; D019143:Evolution, Molecular; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D019596:Wolves / Q000235:genetics*
keywords: adaptation; capture array; climate; genomics; mammals; natural selection