Ancestral genes can control the ability of horizontally acquired loci to confer new traits

PLoS Genet. 2011 Jul;7(7):e1002184. doi: 10.1371/journal.pgen.1002184. Epub 2011 Jul 21.

Abstract

Horizontally acquired genes typically function as autonomous units conferring new abilities when introduced into different species. However, we reasoned that proteins preexisting in an organism might constrain the functionality of a horizontally acquired gene product if it operates on an ancestral pathway. Here, we determine how the horizontally acquired pmrD gene product activates the ancestral PmrA/PmrB two-component system in Salmonella enterica but not in the closely related bacterium Escherichia coli. The Salmonella PmrD protein binds to the phosphorylated PmrA protein (PmrA-P), protecting it from dephosphorylation by the PmrB protein. This results in transcription of PmrA-dependent genes, including those conferring polymyxin B resistance. We now report that the E. coli PmrD protein can activate the PmrA/PmrB system in Salmonella even though it cannot do it in E. coli, suggesting that these two species differ in an additional component controlling PmrA-P levels. We establish that the E. coli PmrB displays higher phosphatase activity towards PmrA-P than the Salmonella PmrB, and we identified a PmrB subdomain responsible for this property. Replacement of the E. coli pmrB gene with the Salmonella homolog was sufficient to render E. coli resistant to polymyxin B under PmrD-inducing conditions. Our findings provide a singular example whereby quantitative differences in the biochemical activities of orthologous ancestral proteins dictate the ability of a horizontally acquired gene product to confer species-specific traits. And they suggest that horizontally acquired genes can potentiate selection at ancestral loci.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial / genetics*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Gene Transfer, Horizontal*
  • Kinetics
  • Magnesium / pharmacology
  • Molecular Sequence Data
  • Phosphorylation
  • Polymyxin B / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transformation, Bacterial

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • PhoQ protein, Bacteria
  • PmrB protein, bacteria
  • PmrD protein, E coli
  • Transcription Factors
  • pmrA protein, Bacteria
  • PhoP protein, Bacteria
  • Magnesium
  • Polymyxin B

Associated data

  • GENBANK/JN032018
  • GENBANK/JN032019
  • GENBANK/JN032020
  • GENBANK/JN032021
  • GENBANK/JN032022
  • GENBANK/JN032023
  • GENBANK/JN032024
  • GENBANK/JN032025