title: Reshuffling genomic landscapes to study the regulatory evolution of Hox gene clusters.
abstract: The emergence of Vertebrata was accompanied by two rounds of whole-genome duplications. This enabled paralogous genes to acquire novel functions with high evolutionary potential, a process suggested to occur mostly by changes in gene regulation, rather than in protein sequences. In the case of Hox gene clusters, such duplications favored the appearance of distinct global regulations. To assess the impact of such "regulatory evolution" upon neo-functionalization, we developed PANTHERE (PAN-genomic Translocation for Heterologous Enhancer RE-shuffling) to bring the entire megabase-scale HoxD regulatory landscape in front of the HoxC gene cluster via a targeted translocation in vivo. At this chimeric locus, Hoxc genes could both interpret this foreign regulation and functionally substitute for their Hoxd counterparts. Our results emphasize the importance of evolving regulatory modules rather than their target genes in the process of neo-functionalization and offer a genetic tool to study the complexity of the vertebrate regulatory genome.
authors.affiliation: National Research Centre Frontiers in Genetics, Department of Genetics and Evolution, University of Geneva, Sciences III, 1211 Geneva 4, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tschopp
authors.forename: Nadine
authors.initials: N
authors.lastname: Fraudeau
authors.forename: Frédérique
authors.initials: F
authors.lastname: Béna
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D023281:Genomics; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D005810:Multigene Family; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers