title: Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6.
abstract: Developmental genetic studies of evolved differences in morphology have led to the hypothesis that cis-regulatory changes often underlie morphological evolution. However, because most of these studies focus on evolved loss of traits, the genetic architecture and possible association with cis-regulatory changes of gain traits are less understood. Here we show that a derived benthic freshwater stickleback population has evolved an approximate twofold gain in ventral pharyngeal tooth number compared with their ancestral marine counterparts. Comparing laboratory-reared developmental time courses of a low-toothed marine population and this high-toothed benthic population reveals that increases in tooth number and tooth plate area and decreases in tooth spacing arise at late juvenile stages. Genome-wide linkage mapping identifies largely separate sets of quantitative trait loci affecting different aspects of dental patterning. One large-effect quantitative trait locus controlling tooth number fine-maps to a genomic region containing an excellent candidate gene, Bone morphogenetic protein 6 (Bmp6). Stickleback Bmp6 is expressed in developing teeth, and no coding changes are found between the high- and low-toothed populations. However, quantitative allele-specific expression assays of Bmp6 in developing teeth in F1 hybrids show that cis-regulatory changes have elevated the relative expression level of the freshwater benthic Bmp6 allele at late, but not early, stages of stickleback development. Collectively, our data support a model where a late-acting cis-regulatory up-regulation of Bmp6 expression underlies a significant increase in tooth number in derived benthic sticklebacks.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Cleves
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Ellis
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Monica T
authors.initials: MT
authors.lastname: Jimenez
authors.affiliation: Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; and.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Nunez
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, Canada V6T 1Z4.
authors.forename: Dolph
authors.initials: D
authors.lastname: Schluter
authors.affiliation: Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; and.
authors.forename: David M
authors.initials: DM
authors.lastname: Kingsley
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; ctmiller@berkeley.edu.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Miller
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D008040:Genetic Linkage; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D008969:Molecular Sequence Data; D050436:Regulatory Elements, Transcriptional; D023701:Smegmamorpha / Q000235:genetics / Q000378:metabolism; D014070:Tooth / Q000254:growth & development*
chemical_list: D055418:Bone Morphogenetic Protein 6; D029941:Fish Proteins
keywords: Gasterosteus; adaptation; craniofacial; polyphyodonty; quantitative genetics