scholarly journals Uncovering Natural Longevity Alleles from Intercrossed Pools of Aging Fission Yeast Cells

2018 ◽  
Author(s):  
David A. Ellis ◽  
Ville Mustonen ◽  
María Rodríguez-López ◽  
Charalampos Rallis ◽  
Michał Malecki ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Genetic Variants ◽  
Genetic Factors ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Untranslated Regions ◽  
Protein Coding ◽  
Chronological Lifespan ◽  
Growth Defects ◽  
Chromosome Ii

ABSTRACTQuantitative traits often show large variation caused by multiple genetic factors. One such trait is the chronological lifespan of non-dividing yeast cells, serving as a model for cellular aging. Screens for genetic factors involved in ageing typically assay mutants of protein-coding genes. To identify natural genetic variants contributing to cellular aging, we exploited two strains of the fission yeast, Schizosaccharomyces pombe, that differ in chronological lifespan. We generated segregant pools from these strains and subjected them to advanced intercrossing over multiple generations to break up linkage groups. We chronologically aged the intercrossed segregant pool, followed by genome sequencing at different times to detect genetic variants that became reproducibly enriched as a function of age. A region on Chromosome II showed strong positive selection during ageing. Based on expected functions, two candidate variants from this region in the long-lived strain were most promising to be causal: small insertions and deletions in the 5’-untranslated regions of ppk31 and SPBC409.08. Ppk31 is an orthologue of Rim15, a conserved kinase controlling cell proliferation in response to nutrients, while SPBC409.08 is a predicted spermine transmembrane transporter. Both Rim15 and the spermine-precursor, spermidine, are implicated in ageing as they are involved in autophagy-dependent lifespan extension. Single and double allele replacement suggests that both variants, alone or combined, have subtle effects on cellular longevity. Furthermore, deletion mutants of both ppk31 and SPBC409.08 rescued growth defects caused by spermidine. We propose that Ppk31 and SPBC409.08 may function together to modulate lifespan, thus linking Rim15/Ppk31 with spermidine metabolism.

scholarly journals Amino acids whose intracellular levels change most during aging alter chronological lifespan of fission yeast

2020 ◽  
Author(s):  
Charalampos Rallis ◽  
Michael Mülleder ◽  
Graeme Smith ◽  
Yan Zi Au ◽  
Markus Ralser ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Fission Yeast ◽  
Yeast Cells ◽  
Total Amino Acid ◽  
Wild Type ◽  
Chronological Lifespan ◽  
Biomarkers Of Aging ◽  
Concentration Changes ◽  
Amino Acid Levels

AbstractAmino acid deprivation or supplementation can affect cellular and organismal lifespan, but we know little about the role of concentration changes in free, intracellular amino acids during aging. Here, we determine free amino-acid levels during chronological aging of non-dividing fission yeast cells. We compare wild-type with long-lived mutant cells that lack the Pka1 protein of the protein kinase A signalling pathway. In wild-type cells, total amino-acid levels decrease during aging, but much less so in pka1 mutants. Two amino acids strongly change as a function of age: glutamine decreases, especially in wild-type cells, while aspartate increases, especially in pka1 mutants. Supplementation of glutamine is sufficient to extend the chronological lifespan of wild-type but not of pka1Δ cells. Supplementation of aspartate, on the other hand, shortens the lifespan of pka1Δ but not of wild-type cells. Our results raise the possibility that certain amino acids are biomarkers of aging, and their concentrations during aging can promote or limit cellular lifespan.

scholarly journals An aging-independent replicative lifespan in a symmetrically dividing eukaryote

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Eric C Spivey ◽  
Stephen K Jones ◽  
James R Rybarski ◽  
Fatema A Saifuddin ◽  
Ilya J Finkelstein
Keyword(s):  
Fission Yeast ◽  
Eukaryotic Cell ◽  
Quantitative Model ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Replicative Lifespan ◽  
Processing Pipeline ◽  
Independent Mechanism ◽  
Genetic Perturbations ◽  
A Cell

The replicative lifespan (RLS) of a cell—defined as the number of cell divisions before death—has informed our understanding of the mechanisms of cellular aging. However, little is known about aging and longevity in symmetrically dividing eukaryotic cells because most prior studies have used budding yeast for RLS studies. Here, we describe a multiplexed fission yeast lifespan micro-dissector (multFYLM) and an associated image processing pipeline for performing high-throughput and automated single-cell micro-dissection. Using the multFYLM, we observe continuous replication of hundreds of individual fission yeast cells for over seventy-five generations. Surprisingly, cells die without the classic hallmarks of cellular aging, such as progressive changes in size, doubling time, or sibling health. Genetic perturbations and drugs can extend the RLS via an aging-independent mechanism. Using a quantitative model to analyze these results, we conclude that fission yeast does not age and that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.

scholarly journals Genetic interactions and transcriptomics implicate fission yeast CTD prolyl isomerase Pin1 as an agent of RNA 3′ processing and transcription termination that functions via its effects on CTD phosphatase Ssu72

2020 ◽  
Vol 48 (9) ◽  
pp. 4811-4826 ◽  
Author(s):  
Ana M Sanchez ◽  
Angad Garg ◽  
Stewart Shuman ◽  
Beate Schwer
Keyword(s):  
Fission Yeast ◽  
Transcriptional Profiling ◽  
Prolyl Isomerase ◽  
Protein Coding ◽  
Peptidyl Prolyl Isomerase ◽  
Growth Defects ◽  
Repressive Effect ◽  
Phosphorylation Pattern ◽  
Ctd Phosphatase ◽  
Polyadenylation Factor

Abstract The phosphorylation pattern of Pol2 CTD Y1S2P3T4S5P6S7 repeats comprises an informational code coordinating transcription and RNA processing. cis–trans isomerization of CTD prolines expands the scope of the code in ways that are not well understood. Here we address this issue via analysis of fission yeast peptidyl-prolyl isomerase Pin1. A pin1Δ allele that does not affect growth per se is lethal in the absence of cleavage-polyadenylation factor (CPF) subunits Ppn1 and Swd22 and elicits growth defects absent CPF subunits Ctf1 and Dis2 and termination factor Rhn1. Whereas CTD S2A, T4A, and S7A mutants thrive in combination with pin1Δ, a Y1F mutant does not, nor do CTD mutants in which half the Pro3 or Pro6 residues are replaced by alanine. Phosphate-acquisition genes pho1, pho84 and tgp1 are repressed by upstream lncRNAs and are sensitive to changes in lncRNA 3′ processing/termination. pin1Δ hyper-represses PHO gene expression and erases the de-repressive effect of CTD-S7A. Transcriptional profiling delineated sets of 56 and 22 protein-coding genes that are down-regulated and up-regulated in pin1Δ cells, respectively, 77% and 100% of which are downregulated/upregulated when the cis-proline-dependent Ssu72 CTD phosphatase is inactivated. Our results implicate Pin1 as a positive effector of 3′ processing/termination that acts via Ssu72.

scholarly journals An aging-independent replicative lifespan in a symmetrically dividing eukaryote

2016 ◽  
Author(s):  
Eric C. Spivey ◽  
Stephen K. Jones ◽  
James R. Rybarski ◽  
Fatema A. Saifuddin ◽  
Ilya J. Finkelstein
Keyword(s):  
Fission Yeast ◽  
Molecular Mechanisms ◽  
Single Cell Analysis ◽  
Eukaryotic Cell ◽  
Culture Conditions ◽  
Cellular Aging ◽  
Yeast Cells ◽  
Replicative Lifespan ◽  
A Cell ◽  
Defined Culture

AbstractThe replicative lifespan (RLS) of a cell—defined as the number of generations a cell divides before death—has informed our understanding of the molecular mechanisms of cellular aging. Nearly all RLS studies have been performed on budding yeast and little is known about the mechanisms of aging and longevity in symmetrically dividing eukaryotic cells. Here, we describe a multiplexed fission yeast (Schizosaccharomyces pombe) lifespan micro-dissector (FYLM); a microfluidic platform for performing automated micro-dissection and high-content single-cell analysis in well-defined culture conditions. Using the FYLM, we directly observe continuous and robust replication of hundreds of individual fission yeast cells for over seventy-five cell divisions. Surprisingly, cells die without any classic hallmarks of cellular aging such as changes in cell morphology, increased doubling time, or reduced sibling health. Genetic perturbations and longevity-enhancing drugs can further extend the replicative lifespan (RLS) via an aging-independent mechanism. We conclude that despite occasional sudden death of individual cells, fission yeast does not age. These results highlight that cellular aging and replicative lifespan can be uncoupled in a eukaryotic cell.

scholarly journals Genetic predictors of participation in optional components of UK Biobank

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessica Tyrrell ◽  
Jie Zheng ◽  
Robin Beaumont ◽  
Kathryn Hinton ◽  
Tom G. Richardson ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Genetic Variants ◽  
Genetic Factors ◽  
Mendelian Randomization ◽  
Genetic Correlations ◽  
Mr Studies ◽  
Uk Biobank ◽  
Factors Affecting ◽  
Participation Bias ◽  
Genetic Predictors

AbstractLarge studies such as UK Biobank are increasingly used for GWAS and Mendelian randomization (MR) studies. However, selection into and dropout from studies may bias genetic and phenotypic associations. We examine genetic factors affecting participation in four optional components in up to 451,306 UK Biobank participants. We used GWAS to identify genetic variants associated with participation, MR to estimate effects of phenotypes on participation, and genetic correlations to compare participation bias across different studies. 32 variants were associated with participation in one of the optional components (P < 6 × 10−9), including loci with links to intelligence and Alzheimer’s disease. Genetic correlations demonstrated that participation bias was common across studies. MR showed that longer educational duration, older menarche and taller stature increased participation, whilst higher levels of adiposity, dyslipidaemia, neuroticism, Alzheimer’s and schizophrenia reduced participation. Our effect estimates can be used for sensitivity analysis to account for selective participation biases in genetic or non-genetic analyses.

Use of electron microscopy to characterize the surfaces of flocculent and nonflocculent yeast cells

1989 ◽  
Vol 35 (12) ◽  
pp. 1081-1086 ◽  
Author(s):  
Byron F. Johnson ◽  
L. C. Sowden ◽  
Teena Walker ◽  
Bong Y. Yoo ◽  
Gode B. Calleja
Keyword(s):  
Electron Microscopy ◽  
Fission Yeast ◽  
Budding Yeast ◽  
The Other ◽  
Yeast Cells ◽  
Scanning Electron Micrographs ◽  
Soft Or ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
Scanning Electron

The surfaces of flocculent and nonflocculent yeast cells have been examined by electron microscopy. Nonextractive preparative procedures for scanning electron microscopy allow comparison in which sharp or softened images of surface details (scars, etc.) are the criteria for relative abundance of flocculum material. Asexually flocculent budding-yeast cells cannot be distinguished from nonflocculent budding-yeast cells in scanning electron micrographs because the scar details of both are well resolved, being hard and sharp. On the other hand, flocculent fission-yeast cells are readily distinguished from nonflocculent cells because fission scars are mostly soft or obscured on flocculent cells, but sharp on nonflocculent cells. Sexually and asexually flocculent fission-yeast cells cannot be distinguished from one another as both are heavily clad in "mucilaginous" or "hairy" coverings. Examination of lightly extracted and heavily extracted flocculent fission-yeast cells by transmission electron microscopy provides micrographs consistent with the scanning electron micrographs.Key words: flocculation, budding yeast, fission yeast, scanning, transmission.

scholarly journals Schizosaccharomyces pombe ras1 and byr1 are functionally related genes of the ste family that affect starvation-induced transcription of mating-type genes.

1990 ◽  
Vol 10 (2) ◽  
pp. 549-560 ◽  
Author(s):  
S A Nadin-Davis ◽  
A Nasim
Keyword(s):  
Gene Family ◽  
Fission Yeast ◽  
Mating Type ◽  
Growth Cycle ◽  
Yeast Cells ◽  
Null Alleles ◽  
Northern Analysis ◽  
Gene Transcript ◽  
Type Gene

We have further investigated the function of the ras1 and byr1 genes, which were previously shown to be critical for sexual differentiation in fission yeast cells. Several physiological similarities between strains containing null alleles of these genes supports the idea that ras1 and byr1 are functionally closely related. Furthermore, we have found that byr1 is allelic to ste1, one of at least 10 genes which when mutated can cause sterility. Since ras1 had previously been found to be allelic to ste5, both ras and byr genes are now clearly shown to be a part of the ste gene family, thus confirming their close functional relationship. The observation that the mating-type loci could overcome the sporulation block of ras1 and byr1 mutant strains prompted investigation of the role of the ras-byr pathway in the induction of the mating-type gene transcripts upon nitrogen starvation. By Northern analysis of RNA preparations from strains carrying wild-type or mutant ras1 alleles and grown to different stages of the growth cycle, we have shown that ras1 plays an important role in inducing the Pi transcript of the mating-type loci and the mei3 gene transcript. These observations provide a molecular basis for the role of the ste gene family, including ras1 and byr1, in meiosis and indicate that further characterization of other ste genes would be very useful for elucidating the mechanism of ras1 function in fission yeast cells.

scholarly journals Genetic susceptibility of opioid receptor genes polymorphism to drug addiction: A candidate-gene association study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Laith N. AL-Eitan ◽  
Doaa M. Rababa’h ◽  
Mansour A. Alghamdi
Keyword(s):  
Drug Addiction ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Healthy Controls ◽  
Candidate Gene Association Study ◽  
Candidate Gene Association ◽  
Addiction Risk ◽  
Arab Descent ◽  
Gene Association Study

Abstract Background Like other complex diseases including drug addiction, genetic factors can interfere with the disease. In this study, three opioid genes (OPRM1, OPRD1, and OPRK1) were examined for an association with drug addiction among Jordanian males. Methods The study involved 498 addicts, in addition to 496 healthy controls and all from Arab descent. Results The findings in this study showed that rs1799971 of the OPRM1 gene was in association with drug addiction for both alleles and genotypes with P-values = 0.002 and 0.01, respectively. In addition, a significant association between the dominant model (A/A vs G/A-G/G) of rs1799971 (OPRM1) and drug addiction (P-value = 0.003, OR = 1.59 (1.17–2.15)) was detected. Moreover, a genetic haplotype (AGGGCGACCCC) of theOPRM1 gene revealed a significant association with drug addiction (P-value = 0.01, OR = 1.56 (1.15–2.12)). We also found that the age of addicts, smoking, and marital status with genetic variants within OPRM1, OPRD1, and OPRK1 genes may be implicated in drug addiction risk. Conclusion We propose that rs1799971 of the OPRM1gene is a genetic risk factor for drug addiction among Jordanian males.

Structure and expression of canary myc family genes

1991 ◽  
Vol 11 (3) ◽  
pp. 1770-1776
Author(s):  
R G Collum ◽  
D F Clayton ◽  
F W Alt
Keyword(s):  
Untranslated Region ◽  
Untranslated Regions ◽  
Coding Region ◽  
Protein Coding ◽  
Coding Regions ◽  
Neuronal Precursors ◽  
Myc Gene ◽  
Mature Neurons

We found that the canary N-myc gene is highly related to mammalian N-myc genes in both the protein-coding region and the long 3' untranslated region. Examined coding regions of the canary c-myc gene were also highly related to their mammalian counterparts, but in contrast to N-myc, the canary and mammalian c-myc genes were quite divergent in their 3' untranslated regions. We readily detected N-myc and c-myc expression in the adult canary brain and found N-myc expression both at sites of proliferating neuronal precursors and in mature neurons.

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