Gal3 Binds Gal80 Tighter than Gal1 Indicating Adaptive Protein Changes Following Duplication

Mol Biol Evol. 2016 Feb;33(2):472-7. doi: 10.1093/molbev/msv240. Epub 2015 Oct 29.


Derived from the yeast whole-genome duplication, Saccharomyces cerevisiae GAL1 and GAL3 encode the catabolic enzyme galactokinase (Gal1) and its transcriptional coinducer (Gal3), whereas the ancestral, preduplicated GAL1 gene performed both functions. Previous studies indicated that divergence was primarily driven by changes in upstream promoter elements, and changes in GAL3's coding region are assumed to be the result of drift. We show that replacement of GAL3's open-reading-frame with GAL1's results in an extended lag phase upon switching to growth on galactose with up to 2.5-fold differences in the initial cell masses. Accordingly, the binding affinity of Gal3 to Gal80 was found to be greater than 10-folds higher than that of Gal1, with both a higher association rate (ka) and lower dissociation (kd) rate. Thus, while changes in the noncoding, regulatory regions were the initial driving force for GAL3's subfunctionalization as a coinducer, adaptive changes in the protein sequence seem to have followed.

Keywords: adaptive evolution; evolution of gene expression; gene duplication; protein evolution; subfunctionalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological*
  • Biological Evolution
  • Galactokinase / genetics
  • Galactokinase / metabolism*
  • Galactose / metabolism
  • Gene Duplication*
  • Kinetics
  • Protein Binding
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • GAL80 protein, S cerevisiae
  • Gal3 protein, S cerevisiae
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • GAL1 protein, S cerevisiae
  • Galactokinase
  • Galactose