Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes

Proc Natl Acad Sci U S A. 2013 May 7;110(19):7748-53. doi: 10.1073/pnas.1304049110. Epub 2013 Apr 22.

Abstract

Lateral gene transfer events between bacteria and animals highlight an avenue for evolutionary genomic loss/gain of function. Herein, we report functional lateral gene transfer in animal parasitic nematodes. Members of the Nematoda are heme auxotrophs, lacking the ability to synthesize heme; however, the human filarial parasite Brugia malayi has acquired a bacterial gene encoding ferrochelatase (BmFeCH), the terminal step in heme biosynthesis. BmFeCH, encoded by a 9-exon gene, is a mitochondrial-targeted, functional ferrochelatase based on enzyme assays, complementation, and inhibitor studies. Homologs have been identified in several filariae and a nonfilarial nematode. RNAi and ex vivo inhibitor experiments indicate that BmFeCH is essential for viability, validating it as a potential target for filariasis control.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bayes Theorem
  • Brugia malayi / enzymology*
  • Brugia malayi / genetics
  • Caenorhabditis elegans / genetics
  • Cloning, Molecular
  • Escherichia coli / metabolism
  • Exons
  • Female
  • Ferrochelatase / genetics*
  • Gene Transfer, Horizontal*
  • Genetic Complementation Test
  • Genome
  • Green Fluorescent Proteins / metabolism
  • In Situ Hybridization
  • Male
  • Microscopy, Confocal
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Phylogeny
  • RNA Interference

Substances

  • Green Fluorescent Proteins
  • Ferrochelatase

Associated data

  • GENBANK/GQ895739
  • GENBANK/GQ895740
  • GENBANK/GQ895741
  • GENBANK/GQ895742
  • GENBANK/GQ895743