Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.11.20.567940

Natural variation in yeast reveals multiple paths for acquiring higher stress resistance

Abstract

BackgroundOrganisms frequently experience environmental stresses that occur in predictable patterns and combinations. For wild Saccharomyces cerevisiae yeast growing in natural environments, cells may experience high osmotic stress when they first enter broken fruit, followed by high ethanol levels during fermentation, and then finally high levels of oxidative stress resulting from respiration of ethanol. Yeast have adapted to these patterns by evolving sophisticated "cross protection" mechanisms, where mild primary doses of one stress can enhance tolerance to severe doses of a different secondary stress. For example, in many yeast strains, mild osmotic or mild ethanol stresses cross protect against severe oxidative stress, which likely reflects an anticipatory response important for high fitness in nature. ResultsDuring the course of genetic mapping studies aimed at understanding the mechanisms underlying natural variation in ethanol-induced cross protection against H2O2, we found that a key H2O2 scavenging enzyme, cytosolic catalase T (Ctt1p), was absolutely essential for cross protection in a wild oak strain. This suggested the absence of other compensatory mechanisms for acquiring H2O2 resistance in that strain background under those conditions. In this study, we found surprising heterogeneity across diverse yeast strains in whether CTT1 function was fully necessary for acquired H2O2 resistance. Some strains exhibited partial dispensability of CTT1 when ethanol and/or salt were used as mild stressors, suggesting that compensatory peroxidases may play a role in acquired stress resistance in certain genetic backgrounds. We leveraged global transcriptional responses to ethanol and salt stresses in strains with different levels of CTT1 dispensability, allowing us to identify possible regulators of these alternative peroxidases and acquired stress resistance in general. ConclusionsUltimately, this study highlights how superficially similar traits can have different underlying molecular foundations and provides a framework for understanding the diversity and regulation of stress defense mechanisms. Author SummaryOrganisms in nature frequently experience environmental stress in predictable patterns. For example, during the summer months in temperate climates, the warmth of the morning sun gradually gives way to high afternoon temperatures. Organisms that can anticipate these predictable patterns to mobilize stress defenses would have an advantage in nature. One way organisms anticipate future stress is through cross protection, where cells exposed to a mild dose of one stress gain the ability to survive an otherwise lethal dose of different stress. To better understand the molecular mechanisms that are responsible cross protection, we have been taking advantage of wild yeast strains that are either more resilient or more sensitive to stresses. During the course of this study, we found that strains with superficially similar levels of cross protection differ in the precise molecular mechanisms that underlie the trait. Our study suggests that different molecular strategies may be important for yielding similar stress resistances under different environmental constraints, and highlights the power of harnessing natural genetic diversity to understand the molecular mechanisms underlying differences in environmental responses.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Scholes, A. N., Stuecker, T. N., Hood, S. E., Locke, C. J., Lewis, J. A.. 2023-11-20. Natural variation in yeast reveals multiple paths for acquiring higher stress resistance. https://doi.org/10.1101/2023.11.20.567940

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A hydrogen-producing mitochondrion in an anaerobic eukaryotrophic rhizarian

Diverse eukaryotes thrive under low oxygen conditions, in part through highly modified mitochondrion-related organelles (MROs) that use alternate metabolic pathways to support ATP production and cofactor recycling. Anaerobic lifestyles have evolved repeatedly across the eukaryotic tree of life, each providing an independent opportunity to understand how eukaryotes adapt to life in low oxygen conditions. Here, we use single-cell transcriptomics to reconstruct the MRO metabolism of PCE SSF, a benthic eukaryotrophic flagellate and the first cultivated representative of Novel Clade 12 (NC12; Rhizaria), an independently anaerobic rhizarian lineage. PCE SSF possesses an anaerobic hydrogen-producing mitochondrion capable of hydrogenosome-type substrate-level phosphorylation. It also retains a nearly complete but likely branched tricarboxylic acid pathway that lacks citrate synthase and malate dehydrogenase. The function of citrate synthase may instead be fulfilled by the typically cytosolic ATP citrate lyase, previously reported in this context only in the anaerobic cercozoan, Brevimastigomonas motovehiculus. Unlike B. motovehiculus, however, PCE SSF retains only Complex II and the NuoE/NuoF subunits of the electron transport chain and lacks a mitochondrial genome. Together, these features indicate an atypical and reduced mitochondrial metabolism, highlighting the diversity of evolutionary solutions to anaerobic energy metabolism in eukaryotes.

genomics↗

A single-nucleus multi-omic atlas of gene regulation across 21 adult human tissues

Diverse human cell types establish specialized functions through lineage- and context-specific regulatory programs. Interpreting non-coding genetic risk requires integrated multi-omic reference maps that directly connect regulatory DNA to cellular expression across human tissues. Here we present a single-nucleus multi-omic atlas comprising 459,856 transcriptomic and chromatin accessibility profiles from 21 adult human tissues and four donors, including paired measurements from 160,688 nuclei. The atlas resolves nine cell lineages, 61 broad cell types and 313 subclusters, and identifies 1,085,062 candidate cis-regulatory elements (cCREs), including 161,270 novel elements absent from ENCODE. Regulatory activity was dominated by cell identity but refined by tissue context. Joint profiling enabled 871,177 cCRE-gene associations and revealed lineage-specific regulatory architectures. Cross-tissue accessibility further identified lineage-restricted and constitutively inaccessible chromatin domains, the latter showing preferential hypomethylation across human cancers. Furthermore, we leverage this dataset to train sequence-to-function models to predict chromatin-accessibility effects for 548,656 fine-mapped variants, identifying 18,133 high-effect variants, including 1,120 broadly active variants. Models trained for eight endothelial subtypes further resolve predicted variant effects across vascular beds. Together, this atlas provides a comprehensive cellular and computational framework for interpreting regulatory sequence, context-dependent gene control, and complex trait genetics across the human body.

genomics↗

The chromosome level genome of the Blueberry Stem Gall Wasp, Hemadas nubilipennis (Hymenoptera: Ormyridae) on lowbush blueberry (Vaccinium angustifolium) reveals repeat-driven expansion

Gall-inducing wasps are emerging models for studying plantinsect coevolution, host manipulation, host plant adaptation, and speciation, yet chromosome-level resources remain scarce for most lineages. The blueberry stem gall wasp (BSGW), Hemadas nubilipennis (Hymenoptera: Ormyridae), is native to North America where it induces galls on both lowbush (Vaccinium angustifolium) and highbush blueberries (V. corymbosum). Recently, BSGW has reached outbreak densities in cultivated highbush production. Given that (a) the biology has been characterized primarily from natural lowbush-associated populations, (b) the absence of genomic resources limits comparative analyses, and (c) populations on cultivated highbush represent a recent host shift, we generated the first chromosome-level genome from wild lowbush blueberry. The BSGW genome consists of five chromosome-scale scaffolds totaling 1.08 Gb (N50 = 218 Mb), the second largest known in Chalcidoidea. Comparative analysis reveals that genome size variation is driven primarily by transposable element proliferation (R = 0.96, p < 0.001), with BSGW exhibiting a high proportion of unclassified TEs. Gene-body methylation is conserved, enriched in exons of broadly expressed core genes, and correlates with gene density. The mitochondrial genome (18,697 bp) exhibits extensive gene rearrangement, and COI sequences reveal 4.35.4% divergence from geographically distant populations, suggesting a complex of cryptic species. Additionally, we assemble a near-complete genome of the endosymbiont Wolbachia pipientis (Supergroup A), which encodes PifA and PifB effectors potentially linked to parthenogenesis. These resources establish a foundation for population genomics, taxonomic revision, and applied management, while providing insights into genome architecture, epigenetics, and symbiont interactions.

genomics↗