GroEL buffers against deleterious mutations

Fares, Mario A.; Ruiz-González, Mario X.; Moya, Andrés; Elena, Santiago F.; Barrio, Eladio

doi:10.1038/417398a

Cited by 248 publications

(231 citation statements)

References 11 publications

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Section: Discussionmentioning

confidence: 99%

“…Over-expression of GroEL, a molecular chaperone of Escherichia coli , can help overcome the accumulation of deleterious mutations that occur in E. coli strains with high mutation rate [20]. In other words, a chaperone can buffer these organisms against deleterious mutations [17,20]. Although the sources of deleterious variation-inbreeding and mutation accumulation-and the chaperones-Hsp90 and GroEL-differ in these two organisms, chaperones have the same qualitative effect in both cases.…”

Section: Discussionmentioning

confidence: 99%

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Hsp90 is important for fecundity, longevity, and buffering of cryptic deleterious variation in wild fly populations

Chen

Wagner

2012

BMC Evol Biol

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BackgroundIn the laboratory, the Drosophila melanogaster heat shock protein Hsp90 can buffer the phenotypic effects of genetic variation. Laboratory experiments either manipulate Hsp90 activity pharmacologically, or they induce mutations with strong effects in the gene Hsp83, the single-copy fly gene encoding Hsp90. It is unknown whether observations from such laboratory experiments are relevant in the wild.ResultsWe here study naturally occurring mutations in Hsp83, and their effects on fitness and phenotypic buffering in flies derived from wild populations. We examined more than 4500 flies from 42 Drosophila populations distributed world-wide for insertions or deletions of mobile DNA in or near the Hsp83 gene. The insertions we observed occur at low population frequencies, and reduce Hsp83 gene expression. In competition experiments, mutant flies performed much more poorly than wild-type flies. Mutant flies were also significantly less fecund and shorter-lived than wild-type flies, as well as less well buffered against cryptic deleterious variation, as we show through inbreeding experiments. Specifically, in Hsp83 mutant flies female fecundity dropped to much lower levels after inbreeding than in wild-type flies. At even slightly elevated temperatures, inbred mutant Hsp83 populations went extinct, whereas inbred wild-type populations persisted.ConclusionsOur work shows that Hsp90, a regulator of the stress response and of signaling, helps buffer deleterious variation in fruit flies derived from wild population, and that its buffering role becomes even more important under heat stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hsp90 is important for fecundity, longevity, and buffering of cryptic deleterious variation in wild fly populations

Chen

Wagner

2012

BMC Evol Biol

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“…It has furthermore been demonstrated that even a simple decrease in the levels of the Hsp90 chaperone may enable a number of otherwise suppressed phenotypic traits to be expressed in natural fruitfly and Arabidopsis populations (Rutherford and Lindquist 1998;Queitsch et al 2002). A similar buffering function against deleterious variations has also been accomplished by experimentally increasing the levels of the bacterial GroEL/ES chaperone complex (Fares et al 2002).…”

Section: Introductionmentioning

confidence: 96%

Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential

Bross

Hansen

et al. 2006

J Hum Genet

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Molecular chaperones assist protein folding, and variations in their encoding genes may be disease-causing in themselves or influence the phenotypic expression of disease-associated or susceptibility-conferring variations in many different genes. We have screened three candidate patient groups for variations in the HSPD1 and HSPE1 genes encoding the mitochondrial Hsp60/Hsp10 chaperone complex: two patients with multiple mitochondrial enzyme deficiency, 61 sudden infant death syndrome cases (MIM: #272120), and 60 patients presenting with ethylmalonic aciduria carrying non-synonymous susceptibility variations in the ACADS gene (MIM: *606885 and #201470). Besides previously reported variations we detected six novel variations: two in the bidirectional promoter region, and one synonymous and three non-synonymous variations in the HSPD1 coding region. One of the non-synonymous variations was polymorphic in patient and control samples, and the rare variations were each only found in single patients and absent in 100 control chromosomes. Functional investigation of the effects of the variations in the promoter region and the non-synonymous variations in the coding region indicated that none of them had a significant impact. Taken together, our data argue against the notion that the chaperonin genes play a major role in the investigated diseases. However, the described variations may represent genetic modifiers with subtle effects.

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“…They are vital for the cell. Chaperones may have a role in neutralizing the consequences of several mutations, in buffering their potential phenotypical changes and making them phenotypically silent (Fares et al, 2002;Queitsch et al, 2002).…”

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confidence: 99%

Senescence‐associated HSP60 expression in normal human skin fibroblasts

et al. 2005

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Normal mammalian fibroblasts cultured in vitro undergo a limited number of divisions before entering a senescent phase in which they can be maintained for long periods but cannot be induced to divide. Senescent cells become unresponsive to growth-promoting signals and exhibit senescent cell morphology with flattened and enlarged cell shape. Several chaperones have a direct effect on cellular senescence. HSP60 has been largely studied in our laboratories and it has been associated with uncontrolled cell proliferation in tumor cells. Since senescence is firmly regulated during cell cycle progression, we wanted to investigate HSP60 protein level during cellular senescence. Our data show that HSP60 increases during the initial stage of senescence and that it is localized in cellular compartments, resembling mitochondria. An increase in HSP60 protein amount is associated with a cell cycle slow-down and it may have a role in cell cycle progression.

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GroEL buffers against deleterious mutations

Cited by 248 publications

References 11 publications

Hsp90 is important for fecundity, longevity, and buffering of cryptic deleterious variation in wild fly populations

Hsp90 is important for fecundity, longevity, and buffering of cryptic deleterious variation in wild fly populations

Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential

Senescence‐associated HSP60 expression in normal human skin fibroblasts

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