Genetic compensation: A phenomenon in search of mechanisms

PLoS Genet. 2017 Jul 13;13(7):e1006780. doi: 10.1371/journal.pgen.1006780. eCollection 2017 Jul.

Abstract

Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.

Publication types

  • Review

MeSH terms

  • Animals
  • Arabidopsis / genetics
  • Dosage Compensation, Genetic*
  • Drosophila / genetics
  • Gene Knockdown Techniques*
  • Gene Knockout Techniques*
  • Mice
  • Models, Animal
  • Mutant Proteins / biosynthesis
  • Mutant Proteins / genetics
  • Transcription, Genetic*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics

Substances

  • Egfl7 protein, zebrafish
  • Mutant Proteins
  • Zebrafish Proteins

Grant support

Research at the Stainier lab is supported by the Max Planck Society, EU and DFG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.