PUBLICATION

Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates

Authors
Kikuta, H., Laplante, M., Navratilova, P., Komisarczuk, A.Z., Engstrom, P.G., Fredman, D., Akalin, A., Caccamo, M., Sealy, I., Howe, K., Ghislain, J., Pezeron, G., Mourrain, P., Ellingsen, S., Oates, A.C., Thisse, C., Thisse, B., Foucher, I., Adolf, B., Geling, A., Lenhard, B., and Becker, T.S.
ID
ZDB-PUB-070330-45
Date
2007
Source
Genome research   17(5): 545-555 (Journal)
Registered Authors
Adolf, Birgit, Becker, Thomas S., Caccamo, Mario, Ellingsen, Ståle, Foucher, Isabelle, Geling, Andrea, Kikuta, Hiroshi, Komisarczuk, Anna Zofia, Laplante, Mary, Mourrain, Philippe, Navratilova, Pavla, Oates, Andrew, Thisse, Bernard, Thisse, Christine
Keywords
none
MeSH Terms
  • Animals
  • Chickens/genetics
  • Conserved Sequence*
  • Evolution, Molecular
  • Gene Duplication
  • Gene Expression Regulation/physiology*
  • Genetic Linkage
  • Genome, Human
  • Humans
  • Synteny*
  • Tetraodontiformes/genetics
  • Zebrafish/genetics*
PubMed
17387144 Full text @ Genome Res.
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 mir9-1 and mir9-5 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes