title: Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes.
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.
authors.affiliation: Division of Molecular Parasitology, New England Biolabs, Inc, Ipswich, MA 01938, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Jacopo
authors.initials: J
authors.lastname: Novelli
authors.forename: Daojun
authors.initials: D
authors.lastname: Jiang
authors.forename: Harry A
authors.initials: HA
authors.lastname: Dailey
authors.forename: Frédéric
authors.initials: F
authors.lastname: Landmann
authors.forename: Louise
authors.initials: L
authors.lastname: Ford
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: Clotilde K S
authors.initials: CK
authors.lastname: Carlow
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Foster
authors.forename: Barton E
authors.initials: BE
authors.lastname: Slatko
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001499:Bayes Theorem; D017178:Brugia malayi / Q000201:enzymology* / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000378:metabolism; D005091:Exons; D005260:Female; D005294:Ferrochelatase / Q000235:genetics*; D022761:Gene Transfer, Horizontal; D005816:Genetic Complementation Test; D016678:Genome; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D034622:RNA Interference
chemical_list: D049452:Green Fluorescent Proteins; D005294:Ferrochelatase