Copy number variants impact phenotype-genotype relationships for adaptation of industrial yeast Saccharomyces cerevisiae

Authors: Liu, Zonglin; HUANG, XIAOQIU - Iowa State University

Submitted to: Applied Microbiology and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2022
Publication Date: 9/19/2022
Citation: Liu, Z., Huang, X. 2022. Copy number variants impact phenotype-genotype relationships for adaptation of industrial yeast Saccharomyces cerevisiae. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-022-12137-0.
DOI: https://doi.org/10.1007/s00253-022-12137-0

Interpretive Summary: The ways that microbes adapt to harsh conditions are not well understood. An ARS scientist at Peoria, Illinois, collaborated with a scientist from Iowa State University to conduct comparative genomic studies, using a robust industrial yeast strain developed and patented by ARS. Several features of the yeast were characterized for resistance against toxic chemicals associated with biofuels conversion from agricultural residues. The researchers found high levels of DNA recombination events in the entire genome for the robust yeast and defined DNA recombination hotspots for specific gene regions. These findings add new knowledge to help understand yeast tolerance and adaptation, and will benefit both basic science and applied research and development communities working toward a bio-based economy.

Technical Abstract: The industrial yeast Saccharomyces cerevisiae possesses a plastic genome enabling its adaptation to varied environment conditions. A more robust strain NRRL Y-50049 was obtained through laboratory adaptation that is resistant to 2-furaldehyde (furfural) and 5-hydroxymethyl-2-furaldehyde (HMF), a major class of toxic chemicals associated with lignocellulose-to-biofuels conversion. A significant amount of knowledge has been achieved underlying mechanisms of the tolerance by transcriptomic and proteomic studies. Recent findings on a limited number of functional SNP (single nucleotide polymorphism) detected in Y-50049 compared with its progenitor NRRL Y-12632 raised doubt of SNP roles on its comprehensive tolerant performance. The genotype-phenotype relationship impacting yeast adaptation is yet unclear. Here we examine copy-number variant (CNV) of Y-50049 compared with its progenitor using genome sequence analysis. We identified COX1 and COB loci as DNA recombination hotspots in the mitochondrial genome in Y-50049, harboring at least nine CNVs with duplication or deletion events with varied sizes ranging from 226 to 446 bp. At least 28 CNVs were detected in the nuclear genome with sizes ranging from 200 to 926 bp in Y-50049. While some genes with CNVs were previously identified as tolerance candidate genes, many genes are not yet well-characterized. For Y-50049, the DNA recombination rate as detected by CNVs was estimated at approximately 0.003 events per kilobase which is six times higher than the mutation rate associated with SNP. CNV appeared to be more important than SNP in genotype-phenotype relationships controlling resistance to toxic chemicals in adaptation of the industrial yeast.