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Title: Horizontally acquired genes in early-diverging pathogenic fungi enable the use of host nucleosides and nucleotides

Horizontal gene transfer (HGT) among bacteria, archaea, and viruses is widespread, but the extent of transfers from these lineages into eukaryotic organisms is contentious. In this work, we systematically identify hundreds of genes that were likely acquired horizontally from a variety of sources by the early-diverging fungal phyla Microsporidia and Cryptomycota. Interestingly, the Microsporidia have acquired via HGT several genes involved in nucleic acid synthesis and salvage, such as those encoding thymidine kinase ( TK), cytidylate kinase, and purine nucleotide phosphorylase. We show that these HGT-derived nucleic acid synthesis genes tend to function at the interface between the metabolic networks of the host and pathogen. Thus, these genes likely play vital roles in diversifying the useable nucleic acid components available to the intracellular parasite, often through the direct capture of resources from the host. Using an in vivo viability assay, we also demonstrate that one of these genes, TK, encodes an enzyme that is capable of activating known prodrugs to their active form, which suggests a possible treatment route for microsporidiosis. We further argue that interfacial genes with well-understood activities, especially those horizontally transferred from bacteria or viruses, could provide medical treatments for microsporidian infections.
Authors:
 [1] ;  [2] ; ORCiD logo [2] ;  [1]
  1. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center (GLBRC), Wisconsin Energy Inst., Genome Center of Wisconsin, J.F. Crow Inst. for the Study of Evolution and Lab. of Genetics
  2. Vanderbilt Univ., Nashville, TN (United States). Dept. of Biological Sciences
Publication Date:
Grant/Contract Number:
FC02-07ER64494; IOS-1401682; DEB-1442113; DEB-1253634; DEB-1442148; 1003258
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 113; Journal Issue: 15; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org:
USDOE; USDA; National Science Foundation (NSF); Alexander von Humboldt Foundation; Pew Charitable Trusts
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; horizontal gene transfer; Microsporidia; Cryptomycota; thymidine kinase; metabolic networks
OSTI Identifier:
1469103

Alexander, William G., Wisecaver, Jennifer H., Rokas, Antonis, and Hittinger, Chris Todd. Horizontally acquired genes in early-diverging pathogenic fungi enable the use of host nucleosides and nucleotides. United States: N. p., Web. doi:10.1073/pnas.1517242113.
Alexander, William G., Wisecaver, Jennifer H., Rokas, Antonis, & Hittinger, Chris Todd. Horizontally acquired genes in early-diverging pathogenic fungi enable the use of host nucleosides and nucleotides. United States. doi:10.1073/pnas.1517242113.
Alexander, William G., Wisecaver, Jennifer H., Rokas, Antonis, and Hittinger, Chris Todd. 2016. "Horizontally acquired genes in early-diverging pathogenic fungi enable the use of host nucleosides and nucleotides". United States. doi:10.1073/pnas.1517242113. https://www.osti.gov/servlets/purl/1469103.
@article{osti_1469103,
title = {Horizontally acquired genes in early-diverging pathogenic fungi enable the use of host nucleosides and nucleotides},
author = {Alexander, William G. and Wisecaver, Jennifer H. and Rokas, Antonis and Hittinger, Chris Todd},
abstractNote = {Horizontal gene transfer (HGT) among bacteria, archaea, and viruses is widespread, but the extent of transfers from these lineages into eukaryotic organisms is contentious. In this work, we systematically identify hundreds of genes that were likely acquired horizontally from a variety of sources by the early-diverging fungal phyla Microsporidia and Cryptomycota. Interestingly, the Microsporidia have acquired via HGT several genes involved in nucleic acid synthesis and salvage, such as those encoding thymidine kinase (TK), cytidylate kinase, and purine nucleotide phosphorylase. We show that these HGT-derived nucleic acid synthesis genes tend to function at the interface between the metabolic networks of the host and pathogen. Thus, these genes likely play vital roles in diversifying the useable nucleic acid components available to the intracellular parasite, often through the direct capture of resources from the host. Using an in vivo viability assay, we also demonstrate that one of these genes, TK, encodes an enzyme that is capable of activating known prodrugs to their active form, which suggests a possible treatment route for microsporidiosis. We further argue that interfacial genes with well-understood activities, especially those horizontally transferred from bacteria or viruses, could provide medical treatments for microsporidian infections.},
doi = {10.1073/pnas.1517242113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 15,
volume = 113,
place = {United States},
year = {2016},
month = {3}
}