1. Genetics and Genomics

Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation

  1. Mahlon A Collins  Is a corresponding author
  2. Gemechu Mekonnen
  3. Frank Wolfgang Albert  Is a corresponding author
  1. Department of Genetics, Cell Biology, and Development, University of Minnesota, United States
https://doi.org/10.7554/eLife.79570
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Cite this article
  1. Mahlon A Collins
  2. Gemechu Mekonnen
  3. Frank Wolfgang Albert
(2022)
Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation
eLife 11:e79570.
https://doi.org/10.7554/eLife.79570
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6 figures, 12 tables and 6 additional files

Figures

Figure 1 with 2 supplements
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UPS N-end rule activity reporters and genetic mapping method.

(A) Schematic of the production and degradation of UPS activity reporters according to the UPS N-end rule. (B) Density plots of the log2 RFP / GFP ratio from 10,000 cells for each of 8 independent biological replicates per strain per reporter for representative Arg/N-end and Ac/N-end pathway reporters. "BY" and "RM" are genetically divergent yeast strains. "BY rpn4Δ", "BY ubr1Δ”, and "BY doa10Δ" carry the indicated gene deletions in the BY background and were used as reporter control strains. (C) The median from each biological replicate in B. was scaled, normalized, and plotted as a stripchart such that y axis values are directly proportional to UPS activity. (D). Heatmap for all strains and N-degrons using data generated as in C. Symbols above the heatmap denote significant UPS activity differences between BY and RM. "*" indicates 0.05 > Tukey HSD p > 1e-6; “#” indicates Tukey HSD p < 1e-6. (E) Schematic of the bulk segregant analysis genetic mapping method used to identify UPS activity QTLs. (F) Density plot of the UPS activity distribution for a genetically diverse mapping population harboring the tryptophan (Trp) N-degron reporter. Dashed vertical lines show the thresholds used to collect cells with extreme UPS activity, which correspond to the high and low UPS activity pools denoted in E. (G) Backplot of the cells collected in F. onto a scatter plot of GFP and RFP.

Figure 1—source data 1

Results of all between-strain comparisons for all N-degron TFTs.

https://cdn.elifesciences.org/articles/79570/elife-79570-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
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Comparison of UPS activity between strains across N-degron reporters.

The -log2 RFP / GFP ratio value was extracted from 10,000 cells from each of 8 independent biological replicates per strain per reporter and converted to Z-scores. High values correspond to high UPS activity and low values correspond to low UPS activity. Tukey HSD p-values for each between strain comparison for each reporter are listed in Figure 1—source data 1.

Figure 1—figure supplement 2
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Overview of the constructs and strain construction steps used to generate yeast strains harboring TFT UPS activity reporters.
Figure 2
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UPS activity QTL mapping results.

(A) Results from the alanine (Ala) N-degron reporter illustrate the results and reproducibility of the method. Asterisks denote QTLs, colored by biological replicate. (B) QTL mapping results for the 20 N-degrons. Colored blocks of 100 kb denote QTLs detected in each of two independent biological replicates, colored according to the direction and magnitude of the effect size (RM allele frequency difference between high and low UPS activity pools). Experimentally validated (boxed) and candidate (unboxed) causal genes for select QTLs are annotated above the plot. (C) Cumulative distributions of the effect size and direction for Arg/N-end and Ac/N-end QTLs. (D) Cumulative distribution of LOD scores for Arg/N-end and Ac/N-end QTLs.

Figure 2—source data 1

All N-end rule QTLs.

"chr" = chromosome, "LOD" = logarithm of the odds, "QTL_CI_left" = left index of QTL confidence interval, "QTL_peak" = peak position of QTL, "QTL_CI_right" = right index of QTL confidence interval.

https://cdn.elifesciences.org/articles/79570/elife-79570-fig2-data1-v2.xlsx
Figure 2—source data 2

All distinct N-end rule QTL regions.

"chr" = chromosome, "QTL_CI_left" = left index of QTL confidence interval, "QTL_peak" = peak position of QTL, "QTL_right_CI" = right index of QTL confidence interval, "LOD" = logarithm of the odds, "RM_AFD" = RM allele frequency difference between high and low UPS activity pools.

https://cdn.elifesciences.org/articles/79570/elife-79570-fig2-data2-v2.xlsx
Figure 3 with 3 supplements
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Substrate-specific effects of UBR1 variants on the degradation of Arg/N-degrons.

(A) Schematic illustrating Ubr1’s role in Arg/N-degron recognition. (B) Multiple causal DNA variants in UBR1 shape UPS activity towards the Trp N-degron. The BY strain was engineered to contain full or partial RM UBR1 alleles as indicated and UPS activity towards the Trp N-degron TFT was measured by flow cytometry. UPS activity was Z-score normalized and scaled relative to the median of a control BY strain engineered to contain the full BY UBR1 allele. Each point in the plot shows the median of 10,000 cells for each of 16 independent biological replicates per strain. p-values at the top of the plot display the Benjamini-Hochberg corrected p-value for the t-test of the indicated strain versus the strain with the BY UBR1 allele. Box plot center lines, box boundaries, and whiskers display the median, interquartile range, and 1.5 times the interquartile range, respectively. (C). Barchart summarizing the effects of RM UBR1 alleles on UPS activity towards the indicated Type 1 and 2 Arg/N-degrons using data generated as in B. p-values in the plot display the Benjamini-Hochberg corrected p-value for the t-test of the indicated strain versus the control strain engineered to contain the BY UBR1 allele. (D) Diagram of the individual BY / RM UBR1 promoter variants. (E) as in C., but for the RM UBR1 promoter and individual BY / RM UBR1 promoter variants. (F) Sequence logo of the Hap5 binding motif created by the causal –469A>T UBR1 promoter variant. (G) Multi-species alignment of the UBR1 promoter at the causal –469A>T variant. Abbreviations: ‘S. para.’, Saccharomyces paradoxus; ‘S. mik.’, Saccharomyces mikatae; ‘S. bay.’, Saccharomyces bayanus; ‘S. arb’, Saccharomyces arboricola; ‘S. pas.’, Saccharomyces pastorianus; ‘S. jur’, Saccharomyces jurei.

Figure 3—figure supplement 1
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Raw UBR1 full gene fine-mapping data.

Raw UBR1 full gene fine-mapping results. The BY strain was engineered to contain full or partial RM UBR1 alleles as indicated and UPS activity towards the indicated Type 1 and Type 2 Arg/N-degron TFTs was measured by flow cytometry. UPS activity was Z-score normalized and scaled relative to the median of a control BY strain engineered to contain the full BY UBR1 allele. Each point in the plot shows the median of 10,000 cells for each of 16 independent biological replicates per strain per reporter. p-values at the top of the plot display the Benjamini-Hochberg-corrected p-value for the t-test of the indicated strain versus the strain with the BY UBR1 allele. Box plot center lines, box boundaries, and whiskers display the median, interquartile range, and 1.5 times the interquartile range, respectively. (A) UPS activity towards the indicated Type 1 Arg/N-degrons. (B) UPS activity towards the indicated Type 2 Arg/N-degrons.

Figure 3—figure supplement 2
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Raw UBR1 promoter fine-mapping data.

Fine-mapping the causal nucleotide in the UBR1 promoter. The BY strain was engineered to carry the RM UBR1 promoter or one of the two single nucleotide BY / RM UBR1 promoter variants as indicated and UPS activity towards the Trp and Phe Type 2 Arg/N-degrons was measured by flow cytometry. UPS activity was Z-score normalized and scaled relative to the median of a control BY strain engineered to contain the full BY UBR1 allele. Each point in the plot shows the median of 10,000 cells for each of 16 independent biological replicates per strain per reporter. p-values at the top of the plot display the Benjamini-Hochberg-corrected p-value for the t-test of the indicated strain versus the strain with the BY UBR1 allele. Box plot center lines, box boundaries, and whiskers display the median, interquartile range, and 1.5 times the interquartile range, respectively.

Figure 3—figure supplement 3
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Population frequency and distribution of the causal UBR1 –469A>T variant.

Population frequencies and distribution of causal variants. Tree diagrams show genetic distance among a global panel of S. cerevisiae isolates with branches colored according to which allele a strain carries. Indicated clades with the BY allele for a causal DNA variant are outlined.

Figure 4 with 4 supplements
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Identification of causal DNA variants for UPS activity in functionally diverse ubiquitin system genes.

(A, E, and I). Schematics showing the role of Nta1 (A), Doa10 (E), and Ubc6 (I) in UPS substrate processing, recognition, and ubiquitination, respectively. (B, F, and J). Location of regulatory and missense BY / RM variants, as well as active sites and functional domains in the proteins encoded by NTA1 (B), DOA10 (F), and UBC6 (J). C., G., and K. Fine-mapping results for NTA1 (C), DOA10 (G), and UBC6 (K). Benjamini-Hochberg corrected p-values are shown for the t-test of the indicated strain versus a control BY strain engineered to contain the BY allele of each gene. AlphaFold predicted protein structures for Nta1 (D), Doa10 (H), and Ubc6 (L) are shown with causal DNA variants, functional domains, active sites, and transmembrane helices highlighted. The inset in L. shows a predicted hydrogen bonding network at residue 229 in the BY Ubc6 protein.

Figure 4—figure supplement 1
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Raw NTA1 fine-mapping data.

The BY strain was engineered to contain full or partial RM NTA1 alleles as indicated and UPS activity towards the Asn Arg/N-degron was measured by flow cytometry. UPS activity was Z-score normalized and scaled relative to the median of a control BY strain engineered to contain the full BY NTA1 allele. Each point in the plot shows the median of 10,000 cells for each of 16 independent biological replicates per strain per reporter. p-values at the top of the plot display the Benjamini-Hochberg-corrected p-value for the t-test of the indicated strain versus the strain with the BY NTA1 allele. Box plot center lines, box boundaries, and whiskers display the median, interquartile range, and 1.5 times the interquartile range, respectively.

Figure 4—figure supplement 2
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Raw DOA10 fine-mapping data.

The BY strain was engineered to contain full or partial RM DOA10 alleles as indicated and UPS activity towards the Gly and Thr Ac/N-degrons was measured by flow cytometry. UPS activity was Z-score normalized and scaled relative to the median of a control BY strain engineered to contain the full BY DOA10 allele. Each point in the plot shows the median of 10,000 cells for each of 16 independent biological replicates per strain per reporter. p-values at the top of the plot display the Benjamini-Hochberg-corrected p-value for the t-test of the indicated strain versus the strain with the BY DOA10 allele. Box plot center lines, box boundaries, and whiskers display the median, interquartile range, and 1.5 times the interquartile range, respectively.

Figure 4—figure supplement 3
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Raw UBC6 fine-mapping data.

The BY strain was engineered to contain full or partial RM UBC6 alleles as indicated and UPS activity towards the Thr and Ala Ac/N-degrons was measured by flow cytometry. UPS activity was Z-score normalized and scaled relative to the median of a control BY strain engineered to contain the full BY UBC6 allele. Each point in the plot shows the median of 10,000 cells for each of 16 independent biological replicates per strain per reporter. p-values at the top of the plot display the Benjamini-Hochberg-corrected p-value for the t-test of the indicated strain versus the strain with the BY UBC6 allele. Box plot center lines, box boundaries, and whiskers display the median, interquartile range, and 1.5 times the interquartile range, respectively.

Figure 4—figure supplement 4
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Population frequencies and distributions of causal variants.

Tree diagrams show genetic distance among a global panel of S. cerevisiae isolates with branches colored according to which allele a strain carries. Indicated clades with the BY allele for a causal DNA variant are outlined.

Figure 5 with 1 supplement
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Proteomic and RNA-seq analysis of the effect of the UBR1 –469A>T promoter variant on gene expression.

(A) Protein fold-change versus statistical significance for BY versus BY UBR1 –469A>T for all detected proteins. Differentially abundant proteins are shown in blue. (B) RNA fold-change versus statistical significance for BY versus BY UBR1 –469A>T for all detected transcripts. Differentially expressed transcripts are shown in yellow. (C) Scatterplot comparing changes in protein and RNA abundance caused by UBR1 –469A>T. "LFC" = log2 fold change.

Figure 5—source data 1

Full proteomics results.

https://cdn.elifesciences.org/articles/79570/elife-79570-fig5-data1-v2.xlsx
Figure 5—source data 2

Full RNA-seq results.

https://cdn.elifesciences.org/articles/79570/elife-79570-fig5-data2-v2.xlsx
Figure 5—figure supplement 1
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Over-represented GO biological processes and Reactome pathways in the set of differentially expressed transcripts.

Barchart of significantly over-represented Gene Ontology Biological Process and Reactome Pathway terms identified using the list of differentially expressed mRNA transcripts between the wild-type BY strain and BY UBR1 –469A>T. The numbers in the bars denote the observed (left) and expected (right) number of genes for a given process or pathway.

Author response image 1
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Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Gene (Saccharomyces cerevisiae)UBR1Saccharomyces Genome Database (SGD)YGR184Cedited to contain
alternative alleles / variants
Gene (S. cerevisiae)DOA10SGDYIL030Cedited to contain
alternative alleles / variants
Gene (S. cerevisiae)UBC6SGDYER100Wedited to contain
alternative alleles / variants
Gene (S. cerevisiae)NTA1SGDYJR062Cedited to contain
alternative alleles / variants
Gene (S. cerevisiae)HIS3SGDYOR202Wselectable marker for genome engineering
Gene (S. cerevisiae)LYP1SGDYNL268Wselectable marker for genome engineering
Strain, strain
background (S. cerevisiae)		BY4741Leonid KruglyakYFA0040Supplementary file 5
Strain, strain
background (S. cerevisiae)		RM11.1aLeonid KruglyakYFA0039Supplementary file 5
Strain, strain
background (S. cerevisiae)		recombinant progeny of BY4741 x RM11.1athis studySFA-Supplementary file 5
Strain, strain
background (S. cerevisiae)		strains with tandem fluorescent timer reportersthis studyYFA-Supplementary file 5
Strain, strain
background (S. cerevisiae)		strains lacking individual ubiquitin-proteasome system genesthis studyYFA-Supplementary file 5
Strain, strain
background (S. cerevisiae)		strains with alternative UPS gene alleles / variantsthis studyYFA-Supplementary file 5
Strain, strain
background (Escherichia coli)		DH5αNew England Biolabsfor plasmid cloning and propagation
Recombinant DNA reagent23 plasmidsthis studyPFA-Supplementary file 4
Recombinant DNA reagentbackbone plasmidAddgene35121
Recombinant DNA reagentbackbone plasmidAddgene41030
Recombinant DNA reagentKanMX cassetteWach et al., 1994;
10.1002/yea.320101310		selectable marker for genome engineering
Recombinant DNA reagentNatMX cassetteWach et al., 1994;
10.1002/yea.320101310		selectable marker for genome engineering
Sequence-based reagent102 oligonucleotidesIntegrated DNA
Techologies		OFA-Supplementary file 3
Commercial assay or kitNextera DNA
Library Prep Kit		IlluminaFC-121–
1030
Commercial assay or kitEB Ultra II
Directional RNA
library kit for Illumina		New England BiolabsE7760
Commercial assay or kitMonarch Gel
Extraction kit		New England BiolabsT1010L
Commercial assay or kitHiFi DNA Assembly
Cloning Kit		New England BiolabsE5520S
Commercial assay or kitTMT10plex Isobaric
Label Reagent Set		ThermoFisher Scientific90110
Commercial assay or kitZR Fungal / Bacterial
RNA Miniprep kit		Zymo ResearchR2014
Commercial assay or kitQuick-96 DNA Plus kitZymo Research
10.1093/bioinformatics/btp324		D4070
Software, algorithmMULTIPOOLEdwards and Gifford, 2012;
10.1186/1471-2105-13-S6-S8
Software, algorithmtrimmomaticBolger et al., 2014
10.1093/bioinformatics/btu170
Software, algorithmkallistoBray et al., 2016;
10.1038/nbt.3519
Software, algorithmPANTHERMi et al., 2021;
10.1093/nar/gkaa1106
Software, algorithmfastpChen et al., 2018;
10.1093/bioinformatics/bty560
Software, algorithmRSeQCWang et al., 2012;
10.1093/bioinformatics/bts356
Software, algorithmScaffoldhttps://www.proteomesoftware.com/
Software, algorithmProteome DiscovererThermo Scientific
Software, algorithmAlphaFoldJumper et al., 2021;
10.1038/s41586-021-03819-2
Software, algorithmInkscapehttps://inkscape.org
OtherLSR II Flow CytometerBDflow cytometry
OtherFACSAria II Cell SorterBDcell sorting
OtherOrbitrap Fusion Tribrid
MS-MS instrument		Thermo Scientificmass spectrometry
OtherNext-Seq 550IlluminaDNA / RNAsequencing
Table 1
Strain genotypes.
Short NameGenotypeAntibiotic ResistanceAuxotrophies
BYMATa his3Δ hoΔhistidine
RMMATα can1Δ::STE2pr-SpHIS5clonNAT, hygromycinhistidine
his3Δ::NatMX hoΔ::HphMX
BY rpn4ΔMATa his3Δ hoΔ rpn4Δ::NatMXclonNAThistidine
BY ubr1ΔMATa his3Δ hoΔ ubr1Δ::NatMXclonNAThistidine
BY doa10ΔMATa his3Δ hoΔ doa10Δ::NatMXclonNAThistidine
Table 2
Media formulations.
Media NameAbbreviationFormulation
Yeast-Peptone-DextroseYPD10 g/L yeast extract
20 g/L peptone
20 g/L dextrose
Synthetic CompleteSC6.7 g/L yeast nitrogen base
1.96 g/L amino acid mix -lys
20 g/L dextrose
Haploid SelectionSGA6.7 g/L yeast nitrogen base
1.74 g/L amino acid mix -his -lys -ura
20 g/L dextrose
SporulationSPO1 g/L yeast extract
10 g/L potassium acetate
0.5 g/L dextrose
Table 3
Flow cytometry and FACS settings.
ParameterLaser Line (nm)Laser Setting (V)Filter
forward scatter (FSC)488500488/10
side scatter (SSC)488275488/10
sfGFP488500525/50
mCherry561615610/20
mRuby561615610/20
Table 4
CRISPR-swap repair templates.
GeneAllele NamePromoterORFTerminator
UBR1UBR1 BYBYBYBY
UBR1UBR1 RMRMRMRM
UBR1UBR1 RM promoterRMBYBY
UBR1UBR1 RM ORFBYRMBY
UBR1UBR1 RM terminatorBYBYRM
UBR1UBR1 -469A>T–469, RM; all other, BYBYBY
UBR1UBR1 -197T>G–197, RM; all other, BYBYBY
DOA10DOA10 BYBYBYBY
DOA10DOA10 RMRMRMRM
DOA10DOA10 Q410EBY1228, RM; all other, BYBY
DOA10DOA10 K1012NBY3036, RM; all other, BYBY
DOA10DOA10 Y1186FBY3557, RM; all other, BYBY
NTA1NTA1 BYBYBYBY
NTA1NTA1 RMRMRMRM
NTA1NTA1 RM promoterRMBYBY
NTA1NTA1 D111ERM331, RM; all other, BYBY
NTA1NTA1 E129GRM386, RM; all other, BYBY
UBC6UBC6 BYBYBYBY
UBC6UBC6 RMRMRMRM
UBC6UBC6 RM promoterRMBYBY
UBC6UBC6 D229GBY1686, RM; all other, BYBY
UBC6UBC6 RM terminatorBYBYRM
Author response table 1
Influence of LOD score significance threshold on the fraction of N-end rule pathway- and N-degron-specific QTLs.
LOD 4.5LOD 3.5LOD 2.5
N-end Rule Pathway-specific QTLs23 / 35 (66%)19 / 35 (54%)16 / 35 (46%)
N-degron-specific QTLs5 / 35 (14%)3 / 35 (9%)3 / 35 (9%)
Author response table 2
Shared QTL Regions and N-degrons Affected.
NQTLchrQTL_CI_leftQTL_peakQTL_CI_rightLODRM_AFDN. N-degrons AffectedN-degrons AffectedPathway-Specific (LOD 4.5)Pathway-Specific (LOD 3.5)Pathway-Specific (LOD 2.5)N-degron-Specific (LOD 4.5)N-degron-Specific (LOD 3.5)N-degron-Specific (LOD 2.5)
1chr_1_a15021394005212245-0.3257Ala, Cys, Gly, Pro, Ser, Thr, ValAc/N-endAc/N-endAc/N-endnonono
2chr_2_a247345051551657393411.10.133Arg, Lys, PheArg/N-endArg/N-endnononono
3chr_2_b25349705856306400108.90.1125Ala, Arg, Asp, Lys, Metnononononono
4chr_4_a429500876621165257.3-0.1084Gln, Glu, Gly, Hisnononononono
5chr_4_b427317532730036260017.50.1522Trp, TyrArg/N-endArg/N-endnononono
6chr_4_c437681742555046356714.30.1566Ala, Phe, Pro, Ser, Thr, Trpnononononono
7chr_4_d43922754982005570008.2-0.1072Asn, AspArg/N-endArg/N-endArg/N-endnonono
8chr_5_a535140037213639625037.50.2487Ala, Cys, Gly, Pro, Ser, Thr, ValAc/N-endAc/N-endAc/N-endnonono
13chr_7_a7420756277510322512.5-0.1552Asn, Thrnononononono
9chr_7_b79817813277917227914.3-0.1567Ala, Cys, Gly, Pro, Ser, Thr, ValAc/N-endnonononono
10chr_7_c7389941418641451318180.16711Ala, Asn, Cys, Gly, Phe, Pro, Ser, Thr, Trp, Tyr, Valnononononono
11chr_7_d784130086970089993415.2-0.1573Arg, Asn, AspArg/N-endArg/N-endArg/N-endnonono
12chr_7_e7856120870980883830107.50.4095His, Leu, Phe, Trp, TyrArg/N-endArg/N-endArg/N-endnonono
15chr_8_a850150980501273006-0.1011TyrArg/N-endArg/N-endArg/N-endTyrTyrTyr
14chr_8_b81188751484001936758.40.1042Asp, LysArg/N-endArg/N-endArg/N-endnonono
17chr_9_a9945501307751680005.10.0992His, LysArg/N-endArg/N-endArg/N-endnonono
16chr_9_b926764129149231541723.50.1956Ala, Gly, Pro, Ser, Thr, ValAc/N-endAc/N-endAc/N-endnonono
18chr_10_a1032390034548237118621.90.18211Ala, Arg, Cys, Gln, Gly, Lys, Phe, Pro, Ser, Trp, Tyrnononononono
19chr_10_b1058977061566064160025.10.1925Ala, Arg, Asn, Cys, Glnnononononono
21chr_11_a11118750156450173600160.1521HisArg/N-endArg/N-endArg/N-endHisnono
20chr_11_b112910303397903887508.4-0.1065Ala, Arg, Cys, Phe, Thrnononononono
22chr_12_a121572001970502268508.20.1262Ala, ProAc/N-endnonononono
23chr_12_b1264441465724167472342.1-0.2511Ala, Cys, Gly, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Valnononononono
24chr_12_c126396376741257026509.70.1084Asp, Gly, His, IleArg/N-endArg/N-endArg/N-endnonono
25chr_13_a13024650589509.6-0.1621AlaAc/N-endAc/N-endnoAlanono
27chr_13_b1331800565257767514.90.1452His, PheArg/N-endArg/N-endArg/N-endnonono
26chr_13_c1326535029616733158416.50.176Arg, Asn, Asp, Glu, His, LysArg/N-endnonononono
29chr_14_a1445073146539448291289.3-0.3428His, Leu, Lys, Met, Phe, Pro, Trp, Tyrnononononono
28chr_14_b1444972547085050402586.70.3362Asp, Thrnononononono
31chr_15_a1513362516386218483120.2-0.1838Arg, Asn, Asp, Glu, His, Lys, Met, Phenononononono
30chr_15_b1534285038805043130010.10.1163Ala, Pro, ThrAc/N-endnonononono
32chr_15_c1552520056152559177510.60.1282Ser, ThrAc/N-endAc/N-endAc/N-endnonono
33chr_15_d155185505697505946508.8-0.0961CysAc/N-endAc/N-endAc/N-endCysCysCys
34chr_16_a1616603019483022207011.60.1215Ala, Gly, Pro, Thr, ValAc/N-endAc/N-endAc/N-endnonono
35chr_16_b1637505040335042895024.5-0.221ProAc/N-endAc/N-endAc/N-endProProPro

  1. Abbreviations: "chr": chromosome, "CI": confidence interval, "RM_AFD": RM allele frequency difference (high – low UPS activity pools)

Author response table 3
Variance Explained by Causal Alleles and Variants.
GeneAlleleN-degronVariance Explained
DOA10K1012NThr0.04
DOA10Q410EThr0.075
DOA10RM_fullThr0.911
DOA10Y1186FThr0.597
DOA10K1012NGly0.608
DOA10Q410EGly0.74
DOA10RM_fullGly0.879
DOA10Y1186FGly0.77
NTA1D111EAsn0.204
NTA1E129GAsn0.764
NTA1RM_fullAsn0.789
NTA1RM_prAsn-0.014
UBC6D229GAla0.717
UBC6RM_fullAla0.666
UBC6RM_prAla-0.027
UBC6RM_termAla0.183
UBC6D229GThr0.762
UBC6RM_fullThr0.928
UBC6RM_prThr0.008
UBC6RM_termThr0.006
UBR1RM_causalPhe0.9
UBR1RM_fullPhe0.917
UBR1RM_nonPhe-0.019
UBR1RM_prPhe0.818
UBR1RM_causalTrp0.937
UBR1RM_fullTrp0.975
UBR1RM_nonTrp0.059
UBR1RM_prTrp0.934
UBR1RM_fullAsn0.438
UBR1RM_ORFAsn0.134
UBR1RM_prAsn-0.012
UBR1RM_termAsn0.064
UBR1RM_fullAsp0.403
UBR1RM_ORFAsp0.101
UBR1RM_prAsp0.097
UBR1RM_termAsp0.048
UBR1RM_fullPhe0.866
UBR1RM_ORFPhe0.343
UBR1RM_prPhe0.316
UBR1RM_termPhe-0.031
UBR1RM_fullTrp0.964
UBR1RM_ORFTrp0.813
UBR1RM_prTrp0.928
UBR1RM_termTrp0.028
Author response table 4
Results of the Sign Test for Lineage-Specific Selection Applied to All BY / RM eQTLs.
LODn_eQTLsn_genesn_pairsreinf_BY_upreinf_RM_upoppos_BY_upoppos_RM_upexcess_reinforcing_pairschi_sq_p
2.43649856432845627757952509–140.818
51969453722081449577698357190.701
109379451411242253204041754.630.934
15612536867451542022791102.240.992
20445230764801081281796518.20.431
253458260933673951274120.60.276
30278822242305465852622.60.145
352310191217844486818200.144
40196316641403541531124.30.0375
4517061474110283342722.90.0261
501475129985212731617.90.0569
Author response table 5
Results of Gene Ontology Enrichment of All cis / trans eQTL pairs.
GOBPIDp_valueOddsRatioExpCountCountTermcategoryLOD
GO:00321972.8E-05315.0630transposition; RNA-mediatedall_reinforcing2.426606803
GO:00150740.000463.19.8720DNA integrationall_reinforcing2.426606803
GO:00064870.000772.711.622protein N-linked glycosylationall_reinforcing2.426606803
GO:00465130.001210.72.227ceramide biosynthetic processall_reinforcing2.426606803
GO:00064580.00293.36.1713'de novo' protein foldingall_reinforcing2.426606803
GO:00189040.0037Inf0.994ether metabolic processall_reinforcing2.426606803
GO:00511310.00399.21.976chaperone-mediated protein complex assemblyall_reinforcing2.426606803
GO:19011350.00451.492.08114carbohydrate derivative metabolic processall_reinforcing2.426606803
GO:00700850.00631.821.2332glycosylationall_reinforcing2.426606803
GO:00610770.00683.93.959chaperone-mediated protein foldingall_reinforcing2.426606803
GO:00066720.0075.42.727ceramide metabolic processall_reinforcing2.426606803
GO:00091010.0071.819.7530glycoprotein biosynthetic processall_reinforcing2.426606803
GO:00162260.00893.15.4311iron-sulfur cluster assemblyall_reinforcing2.426606803
GO:00310700.00936.12.226intronic snoRNA processingall_reinforcing2.426606803
GO:00349650.00936.12.226intronic box C/D snoRNA processingall_reinforcing2.426606803
GO:00321972.8E-05315.0630transposition; RNA-mediatedall_reinforcing2.426606803
GO:00150740.000463.19.8720DNA integrationall_reinforcing2.426606803
GO:00064870.000772.711.622protein N-linked glycosylationall_reinforcing2.426606803
GO:00465130.001210.72.227ceramide biosynthetic processall_reinforcing2.426606803
GO:00064580.00293.36.1713'de novo' protein foldingall_reinforcing2.426606803
GO:00189040.0037Inf0.994ether metabolic processall_reinforcing2.426606803
GO:00511310.00399.21.976chaperone-mediated protein complex assemblyall_reinforcing2.426606803
GO:19011350.00451.492.08114carbohydrate derivative metabolic processall_reinforcing2.426606803
GO:00700850.00631.821.2332glycosylationall_reinforcing2.426606803
GO:00610770.00683.93.959chaperone-mediated protein foldingall_reinforcing2.426606803
GO:00066720.0075.42.727ceramide metabolic processall_reinforcing2.426606803
GO:00091010.0071.819.7530glycoprotein biosynthetic processall_reinforcing2.426606803
GO:00162260.00893.15.4311iron-sulfur cluster assemblyall_reinforcing2.426606803
GO:00310700.00936.12.226intronic snoRNA processingall_reinforcing2.426606803
GO:00349650.00936.12.226intronic box C/D snoRNA processingall_reinforcing2.426606803
GO:00321974E-063.511.5127transposition; RNA-mediatedall_reinforcing5
GO:00150740.000113.77.4818DNA integrationall_reinforcing5
GO:00064580.0013.94.7912'de novo' protein foldingall_reinforcing5
GO:00610770.00115.53.079chaperone-mediated protein foldingall_reinforcing5
GO:00064870.00132.78.8218protein N-linked glycosylationall_reinforcing5
GO:00189040.0013Inf0.774ether metabolic processall_reinforcing5
GO:00465130.00248.51.736ceramide biosynthetic processall_reinforcing5
GO:00705250.00248.51.736tRNA threonylcarbamoyladenosine metabolic processall_reinforcing5
GO:00511310.003810.61.345chaperone-mediated protein complex assemblyall_reinforcing5
GO:00322590.00451.821.2933methylationall_reinforcing5
GO:00461650.00522.211.3220alcohol biosynthetic processall_reinforcing5
GO:00442810.00631.3150.75177small molecule metabolic processall_reinforcing5
GO:00066620.007Inf0.583glycerol ether metabolic processall_reinforcing5
GO:00029490.007Inf0.583tRNA threonylcarbamoyladenosine modificationall_reinforcing5
GO:00332150.007Inf0.583iron assimilation by reduction and transportall_reinforcing5
GO:00461310.00833.83.268pyrimidine ribonucleoside metabolic processall_reinforcing5
GO:00195090.00867.11.535L-methionine salvage from methylthioadenosineall_reinforcing5
GO:00066940.00862.48.0615steroid biosynthetic processall_reinforcing5
GO:00066960.00892.75.9512ergosterol biosynthetic processall_reinforcing5
GO:00066720.00945.12.116ceramide metabolic processall_reinforcing5
GO:00198560.00945.12.116pyrimidine nucleobase biosynthetic processall_reinforcing5
GO:19026520.00982.56.7113secondary alcohol metabolic processall_reinforcing5
GO:00321971.5E-064.56.4420transposition; RNA-mediatedall_reinforcing10
GO:00150747.7E-054.34.6214DNA integrationall_reinforcing10
GO:00189040.00022Inf0.494ether metabolic processall_reinforcing10
GO:00066620.0018Inf0.363glycerol ether metabolic processall_reinforcing10
GO:00062780.00212.76.815RNA-dependent DNA biosynthetic processall_reinforcing10
GO:19020470.00229.11.095polyamine transmembrane transportall_reinforcing10
GO:00461650.00412.66.5614alcohol biosynthetic processall_reinforcing10
GO:00436050.00569.70.854cellular amide catabolic processall_reinforcing10
GO:00195090.00569.70.854L-methionine salvage from methylthioadenosineall_reinforcing10
GO:00724880.0064.91.826ammonium transmembrane transportall_reinforcing10
GO:00158460.00646.11.345polyamine transportall_reinforcing10
GO:00068330.006521.80.493water transportall_reinforcing10
GO:00420440.006521.80.493fluid transportall_reinforcing10
GO:19026520.0072.94.2510secondary alcohol metabolic processall_reinforcing10
GO:00020980.0073.92.437tRNA wobble uridine modificationall_reinforcing10
GO:00064000.0082.37.0514tRNA modificationall_reinforcing10
GO:00090670.00862.55.7112aspartate family amino acid biosynthetic processall_reinforcing10
GO:00066960.009233.779ergosterol biosynthetic processall_reinforcing10
GO:00066940.00962.65.111steroid biosynthetic processall_reinforcing10
GO:00342200.00961.625.2737ion transmembrane transportall_reinforcing10
GO:00322590.011.911.6620methylationall_reinforcing10
GO:00150743.3E-0553.7113DNA integrationall_reinforcing15
GO:00321976.2E-0544.9815transposition; RNA-mediatedall_reinforcing15
GO:00461659.3E-0544.5914alcohol biosynthetic processall_reinforcing15
GO:00062780.000313.55.0714RNA-dependent DNA biosynthetic processall_reinforcing15
GO:19026520.00113.93.3210secondary alcohol metabolic processall_reinforcing15
GO:00195090.001118.70.594L-methionine salvage from methylthioadenosineall_reinforcing15
GO:00705250.001118.70.594tRNA threonylcarbamoyladenosine metabolic processall_reinforcing15
GO:00066960.001642.939ergosterol biosynthetic processall_reinforcing15
GO:00090860.001642.939methionine biosynthetic processall_reinforcing15
GO:00712670.002512.50.684L-methionine salvageall_reinforcing15
GO:00431020.002512.50.684amino acid salvageall_reinforcing15
GO:00436050.002512.50.684cellular amide catabolic processall_reinforcing15
GO:00161280.00333.53.229phytosteroid metabolic processall_reinforcing15
GO:00068110.00341.727.8142ion transportall_reinforcing15
GO:00709000.0034280.393mitochondrial tRNA modificationall_reinforcing15
GO:19008640.0034280.393mitochondrial RNA modificationall_reinforcing15
GO:00066940.00493410steroid biosynthetic processall_reinforcing15
GO:00090660.0052.65.9513aspartate family amino acid metabolic processall_reinforcing15
GO:00441070.00513.33.429cellular alcohol metabolic processall_reinforcing15
GO:00161250.00632.74.7811sterol metabolic processall_reinforcing15
GO:19020470.00757.50.884polyamine transmembrane transportall_reinforcing15
GO:00065310.0079140.493aspartate metabolic processall_reinforcing15
GO:00906460.0079140.493mitochondrial tRNA processingall_reinforcing15
GO:00158040.00825.21.375neutral amino acid transportall_reinforcing15
GO:00162260.00825.21.375iron-sulfur cluster assemblyall_reinforcing15
GO:00986550.00931.912.2921cation transmembrane transportall_reinforcing15
GO:00158400.0095Inf0.22urea transportall_reinforcing15
GO:00343110.0095Inf0.22diol metabolic processall_reinforcing15
GO:00343120.0095Inf0.22diol biosynthetic processall_reinforcing15
GO:00197550.0095Inf0.22one-carbon compound transportall_reinforcing15
GO:00428830.0095Inf0.22cysteine transportall_reinforcing15
GO:00905020.00962.27.1214RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing15
GO:00150741.8E-066.82.8713DNA integrationall_reinforcing20
GO:00321972.8E-065.43.8815transposition; RNA-mediatedall_reinforcing20
GO:00062784.4E-054.63.7313RNA-dependent DNA biosynthetic processall_reinforcing20
GO:00705250.0004724.20.474tRNA threonylcarbamoyladenosine metabolic processall_reinforcing20
GO:00905020.00063.34.7313RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing20
GO:00346540.00171.641.4459nucleobase-containing compound biosynthetic processall_reinforcing20
GO:00065510.001736.10.313leucine metabolic processall_reinforcing20
GO:00709000.001736.10.313mitochondrial tRNA modificationall_reinforcing20
GO:19008640.001736.10.313mitochondrial RNA modificationall_reinforcing20
GO:00158040.00217.61.015neutral amino acid transportall_reinforcing20
GO:00162260.00217.61.015iron-sulfur cluster assemblyall_reinforcing20
GO:00013020.00293.92.568replicative cell agingall_reinforcing20
GO:00442490.00391.591.27111cellular biosynthetic processall_reinforcing20
GO:19015760.0041.592.28112organic substance biosynthetic processall_reinforcing20
GO:00906460.0041180.393mitochondrial tRNA processingall_reinforcing20
GO:00090830.0041180.393branched-chain amino acid catabolic processall_reinforcing20
GO:00063100.0052.28.6917DNA recombinationall_reinforcing20
GO:00158400.006Inf0.162urea transportall_reinforcing20
GO:00197550.006Inf0.162one-carbon compound transportall_reinforcing20
GO:00428830.006Inf0.162cysteine transportall_reinforcing20
GO:00436050.0077120.473cellular amide catabolic processall_reinforcing20
GO:00195090.0077120.473L-methionine salvage from methylthioadenosineall_reinforcing20
GO:00708800.0077120.473fungal-type cell wall beta-glucan biosynthetic processall_reinforcing20
GO:00708790.0077120.473fungal-type cell wall beta-glucan metabolic processall_reinforcing20
GO:00442830.00981.721.1932small molecule biosynthetic processall_reinforcing20
GO:00150741.7E-067.42.412DNA integrationall_reinforcing25
GO:00062781.7E-055.62.9212RNA-dependent DNA biosynthetic processall_reinforcing25
GO:00321972.7E-055.23.0512transposition; RNA-mediatedall_reinforcing25
GO:00905029.7E-054.53.4412RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing25
GO:00346540.00141.829.5445nucleobase-containing compound biosynthetic processall_reinforcing25
GO:00013020.0024.71.887replicative cell agingall_reinforcing25
GO:00442490.0031.664.6182cellular biosynthetic processall_reinforcing25
GO:00158040.00398.40.714neutral amino acid transportall_reinforcing25
GO:00063100.0042.56.4314DNA recombinationall_reinforcing25
GO:19015760.0041.665.1982organic substance biosynthetic processall_reinforcing25
GO:00158400.0042Inf0.132urea transportall_reinforcing25
GO:00197550.0042Inf0.132one-carbon compound transportall_reinforcing25
GO:00705250.004614.60.393tRNA threonylcarbamoyladenosine metabolic processall_reinforcing25
GO:00075680.00633.32.868agingall_reinforcing25
GO:00903050.00872.36.313nucleic acid phosphodiester bond hydrolysisall_reinforcing25
GO:00066960.00933.91.886ergosterol biosynthetic processall_reinforcing25
GO:00150742E-079.31.9912DNA integrationall_reinforcing30
GO:00062781.6E-067.22.3712RNA-dependent DNA biosynthetic processall_reinforcing30
GO:00321973.5E-066.62.5312transposition; RNA-mediatedall_reinforcing30
GO:00905024.5E-066.42.5812RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing30
GO:00063100.000283.44.9514DNA recombinationall_reinforcing30
GO:00903050.001934.6812nucleic acid phosphodiester bond hydrolysisall_reinforcing30
GO:19020470.004513.50.383polyamine transmembrane transportall_reinforcing30
GO:00442490.00461.74559cellular biosynthetic processall_reinforcing30
GO:00346540.00471.820.5932nucleobase-containing compound biosynthetic processall_reinforcing30
GO:19015760.00591.645.4359organic substance biosynthetic processall_reinforcing30
GO:00158460.00710.80.433polyamine transportall_reinforcing30
GO:19030080.00924.61.345organelle disassemblyall_reinforcing30
GO:00150743.7E-0811.21.7412DNA integrationall_reinforcing35
GO:00321974.5E-078.42.1212transposition; RNA-mediatedall_reinforcing35
GO:00062784.5E-078.42.1212RNA-dependent DNA biosynthetic processall_reinforcing35
GO:00905025.9E-078.12.1712RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing35
GO:00063100.0001244.0513DNA recombinationall_reinforcing35
GO:00903050.0002143.7112nucleic acid phosphodiester bond hydrolysisall_reinforcing35
GO:00442490.000622.134.6750cellular biosynthetic processall_reinforcing35
GO:00346540.000772.315.6228nucleobase-containing compound biosynthetic processall_reinforcing35
GO:19015760.0008235.0150organic substance biosynthetic processall_reinforcing35
GO:19020470.003315.30.343polyamine transmembrane transportall_reinforcing35
GO:00158460.005112.20.393polyamine transportall_reinforcing35
GO:00434570.006740.30.142regulation of cellular respirationall_reinforcing35
GO:00066960.00954.51.355ergosterol biosynthetic processall_reinforcing35
GO:00150741.8E-0812.21.6412DNA integrationall_reinforcing40
GO:00905021.7E-079.41.9612RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing40
GO:00321972.2E-079.12.0112transposition; RNA-mediatedall_reinforcing40
GO:00062782.2E-079.12.0112RNA-dependent DNA biosynthetic processall_reinforcing40
GO:00063103.1E-054.83.6113DNA recombinationall_reinforcing40
GO:00903056.7E-054.73.3312nucleic acid phosphodiester bond hydrolysisall_reinforcing40
GO:00158460.001721.70.273polyamine transportall_reinforcing40
GO:19020470.001721.70.273polyamine transmembrane transportall_reinforcing40
GO:00442490.0027228.8741cellular biosynthetic processall_reinforcing40
GO:00346540.00532.112.8822nucleobase-containing compound biosynthetic processall_reinforcing40
GO:00086100.00633.13.479lipid biosynthetic processall_reinforcing40
GO:00066960.006451.235ergosterol biosynthetic processall_reinforcing40
GO:00158040.00879.30.463neutral amino acid transportall_reinforcing40
GO:00150746.3E-0812.31.511DNA integrationall_reinforcing45
GO:00905023.7E-079.91.711RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing45
GO:00062783.7E-079.91.711RNA-dependent DNA biosynthetic processall_reinforcing45
GO:00321976.3E-079.31.811transposition; RNA-mediatedall_reinforcing45
GO:00063102.8E-055.33.112DNA recombinationall_reinforcing45
GO:00903057.6E-055.12.911nucleic acid phosphodiester bond hydrolysisall_reinforcing45
GO:00442490.000392.522.936cellular biosynthetic processall_reinforcing45
GO:19015760.00052.523.236organic substance biosynthetic processall_reinforcing45
GO:19013600.00182.220.732organic cyclic compound metabolic processall_reinforcing45
GO:00346540.00242.41019nucleobase-containing compound biosynthetic processall_reinforcing45
GO:00066960.00296.215ergosterol biosynthetic processall_reinforcing45
GO:00161280.00485.41.25phytosteroid metabolic processall_reinforcing45
GO:00441070.00565.21.25cellular alcohol metabolic processall_reinforcing45
GO:19026520.00565.21.25secondary alcohol metabolic processall_reinforcing45
GO:00551140.00752.47.114oxidation-reduction processall_reinforcing45
GO:00066940.00754.81.35steroid biosynthetic processall_reinforcing45
GO:00461650.00874.61.35alcohol biosynthetic processall_reinforcing45
GO:00066440.00994.41.45phospholipid metabolic processall_reinforcing45
GO:00150742.5E-058.81.328DNA integrationall_reinforcing50
GO:00062785.6E-057.71.478RNA-dependent DNA biosynthetic processall_reinforcing50
GO:00905026.8E-057.51.58RNA phosphodiester bond hydrolysis; endonucleolyticall_reinforcing50
GO:00321970.000126.81.618transposition; RNA-mediatedall_reinforcing50
GO:00063100.000524.72.499DNA recombinationall_reinforcing50
GO:00066960.00118.10.845ergosterol biosynthetic processall_reinforcing50
GO:00161280.0026.90.955phytosteroid metabolic processall_reinforcing50
GO:00903050.0024.22.428nucleic acid phosphodiester bond hydrolysisall_reinforcing50
GO:00441070.00236.60.995cellular alcohol metabolic processall_reinforcing50
GO:19026520.00236.60.995secondary alcohol metabolic processall_reinforcing50
GO:00066940.003361.065steroid biosynthetic processall_reinforcing50
GO:00461650.00385.81.15alcohol biosynthetic processall_reinforcing50
GO:00161250.00754.81.285sterol metabolic processall_reinforcing50
GO:19013620.00942.48.2115organic cyclic compound biosynthetic processall_reinforcing50
Author response table 6
Results of the Sign Test for Lineage-Specific Selection Applied to UPS Gene BY / RM eQTLs.
LODn_eQTLsn_genesn_pairsreinf_by_upreinf_rm_upoppos_by_upoppos_rm_upexcess_reinforcing_pairschi_sq_pgene_set
2.411281869516302920–4.210.815all_UPS_genes
5587176721323231301all_UPS_genes
102501422921287–4.410.428all_UPS_genes
15162105191873–2.740.619all_UPS_genes
2011585100442–3.20.472all_UPS_genes
25907280332-30.475all_UPS_genes
30635650221–1.61all_UPS_genes
35524740121-21all_UPS_genes
403734301200NaNall_UPS_genes
453230201100NaNall_UPS_genes
2.424233143326–0.8571proteasome_genes
514632123225–1.331proteasome_genes
106230400040NaNproteasome_genes
153219200020NaNproteasome_genes
201814100010NaNproteasome_genes
25119100010NaNproteasome_genes
2.48291457613232515-40.812ubiquitin_system_genes
541013757101820901ubiquitin_system_genes
101731052421174-11ubiquitin_system_genes
1511880171772–1.651ubiquitin_system_genes
20886580341-21ubiquitin_system_genes
25735860231-21ubiquitin_system_genes
30544840121-21ubiquitin_system_genes
35444030021–2.670.324ubiquitin_system_genes
403129200200NaNubiquitin_system_genes
452625100100NaNubiquitin_system_genes
2.46181115611161910-11E3_ligase_genes
5300103398121452.670.909E3_ligase_genes
10129791527421.61E3_ligase_genes
158356914401.781E3_ligase_genes
206446502300NaNE3_ligase_genes
254939301200NaNE3_ligase_genes
303733301200NaNE3_ligase_genes
353028200200NaNE3_ligase_genes
402220200200NaNE3_ligase_genes
451817100100NaNE3_ligase_genes
2.4579604200NaNproteasome_chaperone_genes
5318403100NaNproteasome_chaperone_genes
10158201100NaNproteasome_chaperone_genes
15127101000NaNproteasome_chaperone_genes
2096101000NaNproteasome_chaperone_genes
2565101000NaNproteasome_chaperone_genes
3054101000NaNproteasome_chaperone_genes
3543101000NaNproteasome_chaperone_genes
4043101000NaNproteasome_chaperone_genes
4543101000NaNproteasome_chaperone_genes
Author response table 7
Results of Binomial Enrichment Test Applied to QTLs for Individual N-degrons.
N-degronN_QTLsN_RM_upN_BY_upp_value
Ala151050.30
Arg7431.00
Asn7341.00
Asp8530.73
Cys9451.00
Gln3211.00
Glu4221.00
Gly9541.00
His9630.51
Ile1101.00
Leu2111.00
Lys7520.45
Met4130.63
Phe10640.75
Pro13850.58
Ser9630.51
Thr12840.39
Trp6420.69
Tyr7431.00
Val7431.00

Additional files

Supplementary file 1

Allele frequency difference and LOD score traces from QTL mapping experiments.

The plots show the loess-smoothed RM allele frequency difference (high UPS activity pool minus low UPS activity pool) and LOD score traces for the 20 N-degrons. QTLs are marked with asterisks, which are colored by biological replicate.

https://cdn.elifesciences.org/articles/79570/elife-79570-supp1-v2.pdf
Supplementary file 2

Influence of LOD score significance threshold on QTL pathway specificity.

The LOD score and RM allele frequency difference (QTL effect direction) traces for two independent biological replicates of each N-degron are shown for each of 23 pathway-specific QTL regions. Dashed lines at distinct LOD scores illustrate how changing the significance threshold changes the pathway-specificity of a given QTL region.

https://cdn.elifesciences.org/articles/79570/elife-79570-supp2-v2.pdf
Supplementary file 3

Oligonucleotides.

Table listing oligonucleotides used in this study.

https://cdn.elifesciences.org/articles/79570/elife-79570-supp3-v2.xlsx
Supplementary file 4

Plasmids.

Table of plasmids used in this study.

https://cdn.elifesciences.org/articles/79570/elife-79570-supp4-v2.xlsx
Supplementary file 5

Yeast strains.

Table listing all yeast strains used in the study.

https://cdn.elifesciences.org/articles/79570/elife-79570-supp5-v2.xlsx
MDAR checklist
https://cdn.elifesciences.org/articles/79570/elife-79570-mdarchecklist1-v2.docx

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  1. Mahlon A Collins
  2. Gemechu Mekonnen
  3. Frank Wolfgang Albert
(2022)
Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation
eLife 11:e79570.
https://doi.org/10.7554/eLife.79570