title: High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome.
abstract: BACKGROUND
  To balance the demand for uptake of essential elements with their potential toxicity living cells have complex regulatory mechanisms. Here, we describe a genome-wide screen to identify genes that impact the elemental composition ('ionome') of yeast Saccharomyces cerevisiae. Using inductively coupled plasma - mass spectrometry (ICP-MS) we quantify Ca, Cd, Co, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, P, S and Zn in 11890 mutant strains, including 4940 haploid and 1127 diploid deletion strains, and 5798 over expression strains.
  
  
  RESULTS
  We identified 1065 strains with an altered ionome, including 584 haploid and 35 diploid deletion strains, and 446 over expression strains. Disruption of protein metabolism or trafficking has the highest likelihood of causing large ionomic changes, with gene dosage also being important. Gene over expression produced more extreme ionomic changes, but over expression and loss of function phenotypes are generally not related. Ionomic clustering revealed the existence of only a small number of possible ionomic profiles suggesting fitness tradeoffs that constrain the ionome. Clustering also identified important roles for the mitochondria, vacuole and ESCRT pathway in regulation of the ionome. Network analysis identified hub genes such as PMR1 in Mn homeostasis, novel members of ionomic networks such as SMF3 in vacuolar retrieval of Mn, and cross-talk between the mitochondria and the vacuole. All yeast ionomic data can be searched and downloaded at http://www.ionomicshub.org.
  
  
  CONCLUSIONS
  Here, we demonstrate the power of high-throughput ICP-MS analysis to functionally dissect the ionome on a genome-wide scale. The information this reveals has the potential to benefit both human health and agriculture.
authors.affiliation: Institute of Biological and Environmental Science, University of Aberdeen, Scotland, UK. david.salt@abdn.ac.uk
authors.forename: Danni
authors.initials: D
authors.lastname: Yu
authors.forename: John M C
authors.initials: JM
authors.lastname: Danku
authors.forename: Ivan
authors.initials: I
authors.lastname: Baxter
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.forename: Olena K
authors.initials: OK
authors.lastname: Vatamaniuk
authors.forename: Olga
authors.initials: O
authors.lastname: Vitek
authors.forename: Mourad
authors.initials: M
authors.lastname: Ouzzani
authors.forename: David E
authors.initials: DE
authors.lastname: Salt
mesh_terms: D027321:Anion Transport Proteins / Q000235:genetics*; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D007473:Ion Channels / Q000235:genetics; D007477:Ions / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D027321:Anion Transport Proteins; D027682:Cation Transport Proteins; D007473:Ion Channels; D007477:Ions; D027361:Organic Anion Transporters; D029701:Saccharomyces cerevisiae Proteins