Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

Circular DNA of chromosomal origin form from all parts of eukaryotic genomes. In yeast, circular rDNA accumulates as cells divide, contributing to replicative aging. However, little is known about how other chromosome-deri ved circles segregate and contribute to geneticvariation as cells age. We identified circular DNA across the genome of young S. cerevisiae populations and their aged descendants. Young cells had highly diverse circular DNA populations, but lost 94% of the different circular DNA after 20 divisions. Circles present in both young and old cells were characterized by replication origins and included circles from unique regions of the genome, rDNA circles and telomeric Y’ circles. The loss in genetic heterogeneity in aged cells was accompanied by massive accumulation of rDNA circles >95% of all circular DNA. We discovered circles had flexible inherence patterns. Glucose limited conditions selected for cells with glucose-transporter gene circles, [HXT6/7circle], and up to 50% of cells in a population carried them. [HXT6/7circle] cells were eventually substituted by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNA were intermediates in chromosomal amplifications. In conclusion, DNA circles can offer a flexible adaptive solution but cells lose genetic heterogeneity from circular DNA as they undergo replicative aging.

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Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

Nucleic Acids Research ◽

10.1093/nar/gkaa545 ◽

2020 ◽

Vol 48 (14) ◽

pp. 7883-7898 ◽

Cited By ~ 1

Author(s):

Iñigo Prada-Luengo ◽

Henrik D Møller ◽

Rasmus A Henriksen ◽

Qian Gao ◽

Camilla Eggert Larsen ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Genetic Variation ◽

Ribosomal Dna ◽

Replicative Aging ◽

Circular Dna ◽

Circular Dnas ◽

Low Glucose ◽

Chromosomal Amplifications ◽

Mother Cells ◽

Massive Accumulation

Abstract Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y’ regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.

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Faculty Opinions recommendation of Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738243443.793577432 ◽

2020 ◽

Author(s):

Anindya Dutta

Keyword(s):

Saccharomyces Cerevisiae ◽

Genetic Heterogeneity ◽

Replicative Aging ◽

Circular Dna

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Polymorphic human glucose transporter gene (GLUT) is on chromosome 1p31.3----p35

Diabetes ◽

10.2337/diabetes.36.4.546 ◽

1987 ◽

Vol 36 (4) ◽

pp. 546-549 ◽

Cited By ~ 19

Author(s):

T. B. Shows ◽

R. L. Eddy ◽

M. G. Byers ◽

Y. Fukushima ◽

C. R. Dehaven ◽

...

Keyword(s):

Glucose Transporter ◽

Transporter Gene

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Glucose and insulin chronically regulate insulin action via different mechanisms in BC3H1 myocytes. Effects on glucose transporter gene expression

Diabetes ◽

10.2337/diabetes.41.3.274 ◽

1992 ◽

Vol 41 (3) ◽

pp. 274-285 ◽

Cited By ~ 5

Author(s):

P. Mayor ◽

L. Maianu ◽

W. T. Garvey

Keyword(s):

Gene Expression ◽

Insulin Action ◽

Glucose Transporter ◽

Transporter Gene

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Glucose transporter gene expression in rat conceptus during high glucose culture

Diabetologia ◽

10.1007/bf00401139 ◽

1993 ◽

Vol 36 (8) ◽

pp. 696-706 ◽

Cited By ~ 19

Author(s):

Y. Takao ◽

S. Akazawa ◽

K. Matsumoto ◽

H. Takino ◽

M. Akazawa ◽

...

Keyword(s):

Gene Expression ◽

High Glucose ◽

Glucose Transporter ◽

Transporter Gene

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Essential role of glucose transporter GLUT3 for post-implantation embryonic development

Journal of Endocrinology ◽

10.1677/joe-08-0262 ◽

2008 ◽

Vol 200 (1) ◽

pp. 23-33 ◽

Cited By ~ 27

Author(s):

S Schmidt ◽

A Hommel ◽

V Gawlik ◽

R Augustin ◽

N Junicke ◽

...

Keyword(s):

Essential Role ◽

Glucose Transporter ◽

Growth Arrest ◽

Complete Loss ◽

Transporter Gene ◽

Wild Type ◽

Post Implantation ◽

Time Point

Deletion of glucose transporter geneSlc2a3(GLUT3) has previously been reported to result in embryonic lethality. Here, we define the exact time point of growth arrest and subsequent death of the embryo.Slc2a3−/−morulae and blastocysts developed normally, implantedin vivo, and formed egg-cylinder-stage embryos that appeared normal until day 6.0. At day 6.5, apoptosis was detected in the ectodermal cells ofSlc2a3−/−embryos resulting in severe disorganization and growth retardation at day 7.5 and complete loss of embryos at day 12.5. GLUT3 was detected in placental cone, in the visceral ectoderm and in the mesoderm of 7.5-day-old wild-type embryos. Our data indicate that GLUT3 is essential for the development of early post-implanted embryos.

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Lactose-over-Glucose Preference in Bifidobacterium longum NCC2705: glcP, Encoding a Glucose Transporter, Is Subject to Lactose Repression

Journal of Bacteriology ◽

10.1128/jb.188.4.1260-1265.2006 ◽

2006 ◽

Vol 188 (4) ◽

pp. 1260-1265 ◽

Cited By ~ 72

Author(s):

Stephan Parche ◽

Manfred Beleut ◽

Enea Rezzonico ◽

Doris Jacobs ◽

Fabrizio Arigoni ◽

...

Keyword(s):

Glucose Transport ◽

Culture Medium ◽

Glucose Transporter ◽

Glucose Utilization ◽

Bifidobacterium Longum ◽

Global Gene Expression ◽

Dna Arrays ◽

Transporter Gene ◽

Global Gene Expression Profiling ◽

Culture Supernatants

ABSTRACT Analysis of culture supernatants obtained from Bifidobacterium longum NCC2705 grown on glucose and lactose revealed that glucose utilization is impaired until depletion of lactose. Thus, unlike many other bacteria, B. longum preferentially uses lactose rather than glucose as the primary carbon source. Glucose uptake experiments with B. longum cells showed that glucose transport was repressed in the presence of lactose. A comparative analysis of global gene expression profiling using DNA arrays led to the identification of only one gene repressed by lactose, the putative glucose transporter gene glcP. The functionality of GlcP as glucose transporter was demonstrated by heterologous complementation of a glucose transport-deficient Escherichia coli strain. Additionally, GlcP exhibited the highest substrate specificity for glucose. Primer extension and real-time PCR analyses confirmed that expression of glcP was mediated by lactose. Hence, our data demonstrate that the presence of lactose in culture medium leads to the repression of glucose transport and transcriptional down-regulation of the glucose transporter gene glcP. This may reflect the highly adapted life-style of B. longum in the gastrointestinal tract of mammals.

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