Complex modifier landscape underlying genetic background effects
Name
5045.full.pdf
Description
Published version
Size
1.79 MB
Format
Adobe PDF
Checksum (MD5)
ac7124d115668baeb216a2a6ef7a89ab
Author(s)
Hou, Jing
Tan, Guihong
Fink, Gerald R
Andrews, Brenda J.
Boone, Charles
Date Issued
February 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Hou, Jing et al. "Complex modifier landscape underlying genetic background effects." Proceedings of the National Academy of Sciences 116, 11 (February 2019): 5045-5054 © 2019 National Academy of Sciences
Version
Final published version
Abstract
The phenotypic consequence of a given mutation can be influenced by the genetic background. For example, conditional gene essentiality occurs when the loss of function of a gene causes lethality in one genetic background but not another. Between two individual Saccharomyces cerevisiae strains, S288c and Σ1278b, ~1% of yeast genes were previously identified as "conditional essential." Here, in addition to confirming that some conditional essential genes are modified by a nonchromosomal element, we show that most cases involve a complex set of genomic modifiers. From tetrad analysis of S288C/Σ1278b hybrid strains and wholegenome sequencing of viable hybrid spore progeny, we identified complex sets of multiple genomic regions underlying conditional essentiality. For a smaller subset of genes, including CYS3 and CYS4, each of which encodes components of the cysteine biosynthesis pathway, we observed a segregation pattern consistent with a single modifier associated with conditional essentiality. In natural yeast isolates, we found that the CYS3/CYS4 conditional essentiality can be caused by variation in two independent modifiers, MET1 and OPT1, each with roles associated with cellular cysteine physiology. Interestingly, the OPT1 allelic variation appears to have arisen independently from separate lineages, with rare allele frequencies below 0.5%. Thus, while conditional gene essentiality is usually driven by genetic interactions associated with complex modifier architectures, our analysis also highlights the role of functionally related, genetically independent, and rare variants.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1073/pnas.1820915116
