title: Dynamic Evolution of Nitric Oxide Detoxifying Flavohemoglobins, a Family of Single-Protein Metabolic Modules in Bacteria and Eukaryotes.
abstract: Due to their functional independence, proteins that comprise standalone metabolic units, which we name single-protein metabolic modules, may be particularly prone to gene duplication (GD) and horizontal gene transfer (HGT). Flavohemoglobins (flavoHbs) are prime examples of single-protein metabolic modules, detoxifying nitric oxide (NO), a ubiquitous toxin whose antimicrobial properties many life forms exploit, to nitrate, a common source of nitrogen for organisms. FlavoHbs appear widespread in bacteria and have been identified in a handful of microbial eukaryotes, but how the distribution of this ecologically and biomedically important protein family evolved remains unknown. Reconstruction of the evolutionary history of 3,318 flavoHb protein sequences covering the family's known diversity showed evidence of recurrent HGT at multiple evolutionary scales including intrabacterial HGT, as well as HGT from bacteria to eukaryotes. One of the most striking examples of HGT is the acquisition of a flavoHb by the dandruff- and eczema-causing fungus Malassezia from Corynebacterium Actinobacteria, a transfer that growth experiments show is capable of mediating NO resistance in fungi. Other flavoHbs arose via GD; for example, many filamentous fungi possess two flavoHbs that are differentially targeted to the cytosol and mitochondria, likely conferring protection against external and internal sources of NO, respectively. Because single-protein metabolic modules such as flavoHb function independently, readily undergo GD and HGT, and are frequently involved in organismal defense and competition, we suggest that they represent "plug-and-play" proteins for ecological arms races.
authors.affiliation: Department of Biological Sciences, Vanderbilt University.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Wisecaver
authors.affiliation: Laboratory of Genetics, Genome Center of Wisconsin, DOE Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, J. F. Crow Institute for the Study of Evolution, University of Wisconsin-Madison, Madison.
authors.forename: William G
authors.initials: WG
authors.lastname: Alexander
authors.affiliation: Department of Biological Sciences, Vanderbilt University.
authors.forename: Sean B
authors.initials: SB
authors.lastname: King
authors.affiliation: Laboratory of Genetics, Genome Center of Wisconsin, DOE Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, J. F. Crow Institute for the Study of Evolution, University of Wisconsin-Madison, Madison.
authors.forename: Chris Todd
authors.initials: CT
authors.lastname: Hittinger
authors.affiliation: Department of Biological Sciences, Vanderbilt University antonis.rokas@vanderbilt.edu.
authors.forename: Antonis
authors.initials: A
authors.lastname: Rokas
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D000595:Amino Acid Sequence; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D005075:Biological Evolution; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D004093:Dihydropteridine Reductase / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D005658:Fungi / Q000235:genetics; D020440:Gene Duplication; D022761:Gene Transfer, Horizontal; D006420:Hemeproteins / Q000235:genetics* / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010802:Phylogeny
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006420:Hemeproteins; C086193:flavohemoprotein, Bacteria; D009569:Nitric Oxide; D004093:Dihydropteridine Reductase; C076538:hmp protein, E coli; D009247:NADH, NADPH Oxidoreductases
keywords: Malassezia; fungi; gene duplication; gene innovation; gene tree-species phylogeny reconciliation; horizontal gene transfer; phylogenetics