Developmental Gene Amplification and Origin Regulation

Annu Rev Genet. 2004;38:273-304. doi: 10.1146/annurev.genet.37.110801.143851.


Developmentally regulated gene amplification serves to increase the number of templates for transcription, yielding greatly increased protein and/or RNA product for gene(s) at the amplified loci. It is observed with genes that are very actively transcribed and during narrow windows of developmental time where copious amounts of those particular gene products are required. Amplification results from repeated firing of origins at a few genomic loci, while the rest of the genome either does not replicate, or replicates to a lesser extent. As such, amplification is a striking exception to the once-and-only-once rule of DNA replication and may be informative as to that mechanism. Drosophila amplifies eggshell (chorion) genes in the follicle cells of the ovary to allow for rapid eggshell synthesis. Sciara amplifies multiple genes in larval salivary gland cells that encode proteins secreted in the saliva for the pupal case. Finally, Tetrahymena amplifies its rRNA genes several thousand-fold in the creation of the transcriptionally active macronucleus. Due to the ease of molecular and genetic analysis with these systems, the study of origin regulation has advanced rapidly. Comparisons reveal an evolutionarily conserved trans-regulatory apparatus and a similar organization of sequence-specific cis-regulatory replicator and origin elements. The studies indicate a regulatory role for chromatin structure and transcriptionally active genes near the origins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Chromosome Mapping
  • DNA Replication
  • DNA, Ribosomal / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Gene Amplification*
  • Gene Expression Regulation, Developmental*
  • Genes
  • Genes, Developmental
  • Models, Genetic
  • Multigene Family
  • Origin Recognition Complex
  • Phylogeny
  • Replication Origin
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Tetrahymena / genetics


  • DNA, Ribosomal
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Origin Recognition Complex
  • Saccharomyces cerevisiae Proteins