부산대학교 도서관

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.cell.2015.12.007 Byline: Vahan B. Indjeian (1,2,4), Garrett A. Kingman (2), Felicity C. Jones (2,5), Catherine A. Guenther (1,2), Jane Grimwood (3), Jeremy Schmutz (3), Richard M. Myers (3), David M. Kingsley [kingsley@stanford.edu] (1,2,*) Highlights * Altered armor-plate size in sticklebacks maps to a cis-regulatory change in GDF6 gene * Increased GDF6 expression phenocopies armor evolution in transgenic fish * Humans have lost a conserved regulatory element controlling GDF6 expression * Mouse phenotypes suggest that deletion is related to digit shortening in human feet Summary Changes in bone size and shape are defining features of many vertebrates. Here we use genetic crosses and comparative genomics to identify specific regulatory DNA alterations controlling skeletal evolution. Armor bone-size differences in sticklebacks map to a major effect locus overlapping BMP family member GDF6. Freshwater fish express more GDF6 due in part to a transposon insertion, and transgenic overexpression of GDF6 phenocopies evolutionary changes in armor-plate size. The human GDF6 locus also has undergone distinctive regulatory evolution, including complete loss of an enhancer that is otherwise highly conserved between chimps and other mammals. Functional tests show that the ancestral enhancer drives expression in hindlimbs but not forelimbs, in locations that have been specifically modified during the human transition to bipedalism. Both gain and loss of regulatory elements can localize BMP changes to specific anatomical locations, providing a flexible regulatory basis for evolving species-specific changes in skeletal form. Author Affiliation: (1) Howard Hughes Medical Institute (2) Stanford University School of Medicine, Department of Developmental Biology, 279 Campus Drive, Beckman Center B300, Stanford, CA 94305, USA (3) HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA * Corresponding author Article History: Received 16 December 2014; Revised 3 September 2015; Accepted 24 November 2015 (miscellaneous) Published: January 7, 2016 (footnote)4 Present address: MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK (footnote)5 Present address: Friedrich Miescher Laboratory of the Max Planck Society, 72076 TAaAaAeA bingen, Germa