Pan-transcriptome reveals a large accessory genome contribution to gene expression variation in yeast

Nature Genetics, Год журнала: 2024, Номер 56(6), С. 1278 - 1287

Опубликована: Май 22, 2024

Gene expression is an essential step in the translation of genotypes into phenotypes. However, little known about transcriptome architecture and underlying genetic effects at species level. Here we generated analyzed pan-transcriptome ~1,000 yeast natural isolates across 4,977 core 1,468 accessory genes. We found that genome underappreciated driver divergence. Global gene patterns combined with population structure showed variation heritable mainly lies within subpopulation-specific signatures, for which genes are overrepresented. Genome-wide association analyses consistently highlighted associated proportionally more variants larger effect sizes, illustrating critical role on transcriptional landscape between populations.

Язык: Английский

---

CaeNDR, the Caenorhabditis Natural Diversity Resource

Nucleic Acids Research, Год журнала: 2023, Номер 52(D1), С. D850 - D858

Опубликована: Окт. 19, 2023

Abstract Studies of model organisms have provided important insights into how natural genetic differences shape trait variation. These discoveries are driven by the growing availability genomes and expansive experimental toolkits afforded to researchers using these species. For example, Caenorhabditis elegans is increasingly being used identify measure effects variants on traits quantitative genetics. Since 2016, C. Natural Diversity Resource (CeNDR) has facilitated many studies providing an archive wild strains, genome-wide sequence variant data for each strain, a association (GWA) mapping portal community. Here, we present updated platform, (CaeNDR), that enables genetics genomics across three species: elegans, briggsae tropicalis. The CaeNDR platform hosts several databases continually addition new whole-genome annotated variants. Additionally, provides interactive tools explore variation enable GWA mappings. All accessible through freely available web located at caendr.org.

Язык: Английский

---

Evaluating the power and limitations of genome-wide association studies in Caenorhabditis elegans

G3 Genes Genomes Genetics, Год журнала: 2022, Номер 12(7)

Опубликована: Май 10, 2022

Quantitative genetics in Caenorhabditis elegans seeks to identify naturally segregating genetic variants that underlie complex traits. Genome-wide association studies scan the genome for individual are significantly correlated with phenotypic variation a population, or quantitative trait loci. popular choice analyses because loci discovered segregate natural populations. Despite numerous successful mapping experiments, empirical performance of genome-wide study has not, date, been formally evaluated C. elegans. We developed an open-source pipeline called NemaScan and used simulation-based approach provide benchmarks collections wild strains. Simulated heritability complexity determined spectrum detected by studies. Power detect smaller-effect increased number strains sampled from Natural Diversity Resource. Population structure was major driver performance, populations shaped recent selection exhibiting lower false discovery rates than composed more divergent also recapitulated previous experimentally validated variants. Our evaluation provides community critical context pursue using Resource elucidate basis traits

Язык: Английский

---

Histone methyltransferase activity affects metabolism in human cells independently of transcriptional regulation

PLoS Biology, Год журнала: 2023, Номер 21(10), С. e3002354 - e3002354

Опубликована: Окт. 26, 2023

The N-terminal tails of eukaryotic histones are frequently posttranslationally modified. role these modifications in transcriptional regulation is well-documented. However, the extent to which enzymatic processes histone posttranslational modification might affect metabolic less clear. Here, we investigated how methylation metabolism using metabolomics, proteomics, and RNA-seq data from cancer cell lines, primary tumour samples healthy tissue samples. In cancer, expression methyltransferases (HMTs) was inversely correlated activity NNMT, an enzyme previously characterised as a methyl sink that disposes excess groups carried by universal donor S-adenosyl methionine (SAM or AdoMet). tissues, levels alternative sink, PEMT. These associations affected multiple marks on chromatin genome-wide but had no detectable impact regulation. We show HMTs with variety different transcription co-regulated Retinoblastoma (Rb) suppressor human cells. Rb-mutant cancers increased total HMT down-regulation NNMT . Together, our results suggest affects SAM metabolism, independent

Язык: Английский

---

Pan-transcriptome reveals a large accessory genome contribution to gene expression variation in yeast

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 18, 2023

Summary Gene expression is an essential step in the translation of genotypes into phenotypes. However, little known about transcriptome architecture and underlying genetic effects at a species-level. Here, we generated analyzed pan-transcriptome ∼1,000 yeast natural isolates across 4,977 core 1,468 accessory genes. We found that genome underappreciated driver divergence. Global gene patterns combined with population structure show heritable variation mainly lies within subpopulation-specific signatures, for which genes are overrepresented. Genome-wide association analyses consistently highlight associated proportionally more variants larger effect sizes, illustrating critical role on transcriptional landscape between populations.

Язык: Английский

---

Simple Worm, Complex Disorder: Studying Down Syndrome Mechanisms in the Unassuming Model C. elegans

Опубликована: Янв. 1, 2025

Язык: Английский

---

Independent mechanisms of benzimidazole resistance across Caenorhabditis nematodes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Benzimidazoles (BZs), a widely used class of anthelmintic drugs, target beta-tubulin proteins, disrupt microtubule formation, and cause nematode death. In parasitic species, mutations in genes ( e.g. , isotype-1 beta-tubulin) are predicted to inhibit BZ binding associated with resistance. Similarly, the free-living Caenorhabditis elegans an ortholog, ben-1 primary drivers The recurrent association resistance beta-tubulins suggests that is repeatedly caused by genes, example repeated evolution drug across species. To evaluate hypothesis mediated beta-tubulin, we identified alleles wild strains from three species: C. briggsae tropicalis . We hypothesized that, if these species experienced similar selective pressures, they would evolve BZs any tbb-1 tbb-2 ). Using high-throughput development assays, tested found heterogeneous set variants were only two encode premature stop codon (W21stop) missense substitution (Q134H), but neither was might have evolved other or not Our findings reveal lack highlight importance defining mechanisms outside beta-tubulins.

Язык: Английский

---

Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast

Molecular Systems Biology, Год журнала: 2024, Номер 20(4), С. 362 - 373

Опубликована: Фев. 14, 2024

Unraveling the genetic sources of gene expression variation is essential to better understand origins phenotypic diversity in natural populations. Genome-wide association studies identified thousands variants involved variation, however, detected only explain part heritability. In fact, such as low-frequency and structural (SVs) are poorly captured studies. To assess impact these on we explored a half-diallel panel composed 323 hybrids originated from pairwise crosses 26 Saccharomyces cerevisiae isolates. Using short- long-read sequencing strategies, established an exhaustive catalog single nucleotide polymorphisms (SNPs) SVs for this panel. Combining dataset with transcriptomes all hybrids, comprehensively mapped SNPs associated variation. While exhibit higher effect size overrepresentation compared common ones. These results reinforce importance dissecting heritability complex traits comprehensive at population level.

Язык: Английский

---

Non-additive genetic components contribute significantly to population-wide gene expression variation

Cell Genomics, Год журнала: 2023, Номер 4(1), С. 100459 - 100459

Опубликована: Дек. 4, 2023

Gene expression variation, an essential step between genotype and phenotype, is collectively controlled by local (cis) distant (trans) regulatory changes. Nevertheless, how these elements differentially influence gene variation remains unclear. Here, we bridge this gap analyzing the transcriptomes of a large diallel panel consisting 323 unique hybrids originating from genetically divergent Saccharomyces cerevisiae isolates. Our analysis across 5,087 transcript abundance traits showed that non-additive components account for 36% variance on average. By comparing allele-specific read counts in parent-hybrid trios, found trans-regulatory changes underlie majority population. Remarkably, most cis-regulatory variations are also exaggerated or attenuated additional trans effects. Overall, transcriptome globally buffered at genetic level mainly due to

Язык: Английский

---

Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion

Journal of Inorganic Biochemistry, Год журнала: 2024, Номер 257, С. 112593 - 112593

Опубликована: Май 8, 2024

Язык: Английский

---