Comparative genomics of the Hedgehog loci in chordates and the origins of Shh regulatory novelties.
The origin and evolution of the complex regulatory landscapes of some vertebrate developmental genes, often spanning hundreds of Kbp and including neighboring genes, remain poorly understood. The Sonic Hedgehog (Shh) genomic regulatory block (GRB) is one of the best functionally characterized examples, with several discrete enhancers reported within its introns, vast upstream gene-free region and neighboring genes (Lmbr1 and Rnf32). To investigate the origin and evolution of this GRB, we sequenced and characterized the Hedgehog (Hh) loci from three invertebrate chordate amphioxus species, which share several early expression domains with Shh. Using phylogenetic footprinting within and between chordate lineages, and reporter assays in zebrafish probing >30 Kbp of amphioxus Hh, we report large sequence and functional divergence between both groups. In addition, we show that the linkage of Shh to Lmbr1 and Rnf32, necessary for the unique gnatostomate-specific Shh limb expression, is a vertebrate novelty occurred between the two whole-genome duplications.
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. mirimia@gmail.com
Manuel
M
Irimia
Jose L
JL
Royo
Demian
D
Burguera
Ignacio
I
Maeso
José L
JL
Gómez-Skarmeta
Jordi
J
Garcia-Fernandez
D000818:Animals; D030801:Animals, Genetically Modified; D002816:Chordata, Nonvertebrate / Q000145:classification / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D026801:Synteny; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
D053823:Hedgehog Proteins; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins