|Yu, Danni -|
|Danku, John -|
|Kim, Sungjin -|
|Vatamaniuk, Olena -|
|Vitek, Olga -|
|Ouzzani, Mourad -|
|Salt, David -|
Submitted to: Biomed Central (BMC) Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 26, 2012
Publication Date: November 14, 2012
Citation: Yu, D., Danku, J., Baxter, I.R., Kim, S., Vatamaniuk, O., Vitek, O., Ouzzani, M., Salt, D. 2012. High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome. Biomed Central (BMC) Genomics. 13:623. Interpretive Summary: Brewers yeast is often used as a model single celled organism as it is easy to grow, and manipulate and large collections of strains with single genes deleted or overexpressed are available. We used a high throughput elemental profiling system to quantify the content of elements (the ionome), including nutrients such as calcium, iron and zink as well as toxic elements such cadmium in ~12,000 mutant strains. This large, high quality, dataset allowed us to identify roles for sub cellular bodies such as the mitochondria and vacuole and biochemical pathways involved in protein trafficking in regulating the elemental content of the cell. We were also able to combine this data with other large scale datasets to perform network analysis, which allowed us to assign novel functions to some genes. Overall, this large, publically available (www.ionomicshub.org) dataset demonstrates the power of high-throughput elemental profiling 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.
Technical Abstract: 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 overexpression strains. We identified 1065 strains with an altered ionome, including 584 haploid and 35 diploid deletion strains, and 446 overexpression strains. Disruption of protein metabolism or trafficking has the highest likelihood of causing large ionomic changes, with gene dosage also being important. Gene overexpression produced more extreme ionomic changes, but overexpression 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 www.ionomicshub.org. 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.