title: Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates.
abstract: We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated "bystander" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.
authors: Sars Centre for Marine Molecular Biology, University of Bergen, 5008 Bergen, Norway.
authors: Hiroshi
authors: H
authors: Kikuta
authors: Mary
authors: M
authors: Laplante
authors: Pavla
authors: P
authors: Navratilova
authors: Anna Z
authors: AZ
authors: Komisarczuk
authors: Pär G
authors: PG
authors: Engström
authors: David
authors: D
authors: Fredman
authors: Altuna
authors: A
authors: Akalin
authors: Mario
authors: M
authors: Caccamo
authors: Ian
authors: I
authors: Sealy
authors: Kerstin
authors: K
authors: Howe
authors: Julien
authors: J
authors: Ghislain
authors: Guillaume
authors: G
authors: Pezeron
authors: Philippe
authors: P
authors: Mourrain
authors: Staale
authors: S
authors: Ellingsen
authors: Andrew C
authors: AC
authors: Oates
authors: Christine
authors: C
authors: Thisse
authors: Bernard
authors: B
authors: Thisse
authors: Isabelle
authors: I
authors: Foucher
authors: Birgit
authors: B
authors: Adolf
authors: Andrea
authors: A
authors: Geling
authors: Boris
authors: B
authors: Lenhard
authors: Thomas S
authors: TS
authors: Becker
mesh_terms: D000818:Animals; D002645:Chickens / Q000235:genetics; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020440:Gene Duplication; D005786:Gene Expression Regulation / Q000502:physiology*; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D026801:Synteny; D023721:Tetraodontiformes / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*