OPEN G3 (Bethesda, Md.) | 21 Sep 2013
MG Norris, SC Lovell and D Delneri
Variation in gene copy number can significantly affect organism fitness. When one allele is missing in a diploid, the phenotype can be compromised, due to haploinsufficiency. In this work we identified associations between Saccharomyces cerevisiae gene properties and genome-scale haploinsufficiency phenotypes from earlier work. We compared the haploinsufficiency profiles against 23 gene properties and found that genes with (i) higher level of connectivity (degree) in a protein-protein interaction network, (ii) higher genetic interaction degree, (iii) greater gene sequence conservation, and (iv) higher protein expression were significantly more likely to be haploinsufficient. Additionally, haploinsufficiency showed negative relationships with (v) cell cycle regulation and (vi) promoter sequence conservation. We exploited the aforementioned associations using Linear Discriminant Analysis to predict haploinsufficiency in existing data and guide experimental identification of 6 novel haploinsufficient phenotypes, previously undetected in genome-scale screenings. Using a similar approach we identified significant relationships between haploinsufficiency and two gene properties in Schizosaccharomyces pombe, relationships that hold despite the lack of conserved HI between S. cerevisiae and Sz. pombe orthologue pairs. These data suggest associations between haploinsufficiency and gene properties are conserved among hemiascomycetes yeasts. The relationships and predictive model presented here are a useful step towards understanding haploinsufficiency and its underlying mechanisms.
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