title: The genomic architecture of population divergence between subspecies of the European rabbit.
abstract: The analysis of introgression of genomic regions between divergent populations provides an excellent opportunity to determine the genetic basis of reproductive isolation during the early stages of speciation. However, hybridization and subsequent gene flow must be relatively common in order to localize individual loci that resist introgression. In this study, we used next-generation sequencing to study genome-wide patterns of genetic differentiation between two hybridizing subspecies of rabbits (Oryctolagus cuniculus algirus and O. c. cuniculus) that are known to undergo high rates of gene exchange. Our primary objective was to identify specific genes or genomic regions that have resisted introgression and are likely to confer reproductive barriers in natural conditions. On the basis of 326,000 polymorphisms, we found low to moderate overall levels of differentiation between subspecies, and fewer than 200 genomic regions dispersed throughout the genome showing high differentiation consistent with a signature of reduced gene flow. Most differentiated regions were smaller than 200 Kb and contained very few genes. Remarkably, 30 regions were each found to contain a single gene, facilitating the identification of candidate genes underlying reproductive isolation. This gene-level resolution yielded several insights into the genetic basis and architecture of reproductive isolation in rabbits. Regions of high differentiation were enriched on the X-chromosome and near centromeres. Genes lying within differentiated regions were often associated with transcription and epigenetic activities, including chromatin organization, regulation of transcription, and DNA binding. Overall, our results from a naturally hybridizing system share important commonalities with hybrid incompatibility genes identified using laboratory crosses in mice and flies, highlighting general mechanisms underlying the maintenance of reproductive barriers.
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal; Departamento de Biologia, Faculdade de Ciências Universidade do Porto, Porto, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carneiro
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany; Princeton University, Lewis Sigler Institute for Integrative Genomics, Princeton, New Jersey, United States of America.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Albert
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Afonso
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal; Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Pereira
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany; Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tuebingen, Germany.
authors.forename: Hernan
authors.initials: H
authors.lastname: Burbano
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Campos
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Melo-Ferreira
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal; IREC, Instituto de Investigación en Recursos Cinegéticos (CSIC-UCLM-JCCM), Ciudad Real, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Blanco-Aguiar
authors.affiliation: Instituto de Investigación en Recursos Cinegéticos (CSIC-UCLM-JCCM), Departamento de Zoología, Universidad de Córdoba, Córdoba, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Villafuerte
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Nachman
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany; Division of Biological Sciences, The University of Montana, Missoula, Montana, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Good
authors.affiliation: CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Campus Agrário de Vairão, Vairão, Portugal; Departamento de Biologia, Faculdade de Ciências Universidade do Porto, Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Ferrand
mesh_terms: D000818:Animals; D002503:Centromere; D005060:Europe; D051456:Gene Flow; D049810:Genetic Speciation; D005828:Genetics, Population; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006824:Hybridization, Genetic; D051379:Mice; D011817:Rabbits; D060047:Reproductive Isolation; D014960:X Chromosome