University of Toronto

Gabriel Musso

 
 

The majority of my PhD research has focused on the study of protein interaction networks, specifically how duplicated genes fit within them.  Immediately following a gene duplication event there is a period of enhanced selection acting on either one or both duplicates (paralogs) which results in some extent of functional divergence.  However, as redundancy among extant duplicates is thought to confer genomic robustness, a consequent question is: how much functional overlap exists between that subset of duplicates that are retained over long periods of evolutionary time? To examine this issue we initially determined the extent of shared protein interactions and protein complex membership for paralogous gene pairs resulting from an ancient Whole Genome Duplication (WGD) event in yeast, finding retained functional overlap to be substantial among this group.  Accordingly, through survey of aggravating genetic interactions between 399 WGD-resultant paralog pairs, we demonstrated that paralogs exhibit a high frequency (roughly 40%) of epistasis.  Further, exposure to a limited number of stressors confirmed that additional instances of epistasis were only observable under alternate conditions.  As only a small number of stress conditions were tested, the high frequency of genetic interactions we report appears to be a minimum estimate of the true extent of epistasis among WGD paralogs.  Currently my work focuses primarily on determining the remaining instances of epistasis among WGD paralogs, and also explores extrapolations towards duplicates retained in mammals.

 

paralogs, protein complexes and epistasis

Left is a disease interaction network pictured using Cytoscape.  Right are network diagrams demonstrating functional guilt-by-association (top) and small-scale protein binding (bottom left).  Bottom right are yeast cells grown for Random Spore Analysis.

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