Single-cell imaging of protein dynamics of paralogs reveals sources of gene retention
Gene duplication is common across the Tree of Life and contributes to genomic robustness. In this study, we examined changes in the subcellular localization and abundance of proteins in response to the deletion of their paralogs originating from the whole-genome duplication event, which is a largely unexplored mechanism of functional divergence. We performed a systematic single-cell imaging analysis of protein dynamics and screened subcellular redistribution of proteins. We find that 20% of proteins exhibit redistribution, of which 1/3 relocalized and 1/2 changed in abundance. Paralogs showed dependency, whereby proteins required their paralog to maintain their endogenous abundance or localization, 2-fold more often than compensation. Network feature analysis suggested the importance of functional redundancy and rewiring of protein and genetic interactions underlying redistribution paralog response. Translation of alternate protein isoform emerged as a compensatory mechanism. This study provides insight into paralog retention and evolutionary forces that shape genomes.
Authors
- Oren Kraus (ORCID: https://orcid.org/0000-0002-6328-9492)
- Benjamin Grys
- Charles Boone (ORCID: https://orcid.org/0000-0002-3542-6760)
- Dmytro Fishman (ORCID: https://orcid.org/0000-0002-4644-8893)
- Brittany M. Greco
- Kyle Wang (ORCID: https://orcid.org/0000-0003-3699-9285)
- Rohan Dandage (ORCID: https://orcid.org/0000-0002-6421-2067)
- Mikhail Papkov (ORCID: https://orcid.org/0000-0001-8423-9630)
- Guillaume Bourque (ORCID: https://orcid.org/0000-0002-3933-9656)
- Erin B. Styles
- Gerardo Zapata (ORCID: https://orcid.org/0000-0002-3721-0488)
- Leopold Parts (ORCID: https://orcid.org/0000-0002-2618-670X)
- Elena Kuzmin (ORCID: https://orcid.org/0000-0002-7479-9308)
- Helena Friesen (ORCID: https://orcid.org/0000-0001-8925-7440)
- François Lefebvre (ORCID: https://orcid.org/0000-0002-4440-7131)
- Brenda J. Andrews
- Vanessa Tolentino Pereira
Institutions
- University of Toronto (CA)
- McGill University Health Centre (CA)
- Wellcome Sanger Institute (GB)
- Genome Canada (CA)
- McGill Genome Centre (CA)
- McGill University (CA)
- University of Tartu (EE)
- Concordia University (CA)
Publication Details
- Journal
- iScience
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1016/j.isci.2025.112771
- Citations
- 2
- Primary Topic
- Fungal and yeast genetics research
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Wellcome Trust
- Canada Foundation for Innovation
- Canada Research Chairs
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada