Age- and Temperature-Dependent Somatic Mutation Accumulation in
Using a transgenic mouse model harboring a mutation reporter gene that can be efficiently recovered from genomic DNA, we previously demonstrated that mutations accumulate in aging mice in a tissue-specific manner. Applying a recently developed, similar reporter-based assay in Drosophila melanogaster, we now show that the mutation frequency at the lacZ locus in somatic tissue of flies is about three times as high as in mouse tissues, with a much higher fraction of large genome rearrangements. Similar to mice, somatic mutations in the fly also accumulate as a function of age, but they do so much more quickly at higher temperature, a condition which in invertebrates is associated with decreased life span. Most mutations were found to accumulate in the thorax and less in abdomen, suggesting the highly oxidative flight muscles as a possible source of genotoxic stress. These results show that somatic mutation loads in short-lived flies are much more severe than in the much longer-lived mice, with the mutation rate in flies proportional to biological rather than chronological aging.
Vyšlo v časopise:
Age- and Temperature-Dependent Somatic Mutation Accumulation in. PLoS Genet 6(5): e32767. doi:10.1371/journal.pgen.1000950
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000950
Souhrn
Using a transgenic mouse model harboring a mutation reporter gene that can be efficiently recovered from genomic DNA, we previously demonstrated that mutations accumulate in aging mice in a tissue-specific manner. Applying a recently developed, similar reporter-based assay in Drosophila melanogaster, we now show that the mutation frequency at the lacZ locus in somatic tissue of flies is about three times as high as in mouse tissues, with a much higher fraction of large genome rearrangements. Similar to mice, somatic mutations in the fly also accumulate as a function of age, but they do so much more quickly at higher temperature, a condition which in invertebrates is associated with decreased life span. Most mutations were found to accumulate in the thorax and less in abdomen, suggesting the highly oxidative flight muscles as a possible source of genotoxic stress. These results show that somatic mutation loads in short-lived flies are much more severe than in the much longer-lived mice, with the mutation rate in flies proportional to biological rather than chronological aging.
Zdroje
1. VijgJ
CampisiJ
2008 Puzzles, promises and a cure for ageing. Nature 454 1065 1071
2. SzilardL
1959 On the nature of the aging process. Proc Natl Acad Sci U S A 45 30 45
3. FaillaG
1958 The aging process and carcinogenesis. Annals of the New York Academy of Science 71 1124 1135
4. RussellLB
SelbyPB
von HalleE
SheridanW
ValcovicL
1981 Use of the mouse spot test in chemical mutagenesis: interpretation of past data and recommendations for future work. Mutat Res 86 355 379
5. KayaB
MarcosR
YanikogluA
CreusA
2004 Evaluation of the genotoxicity of four herbicides in the wing spot test of Drosophila melanogaster using two different strains. Mutat Res 557 53 62
6. BoerrigterME
DolleME
MartusHJ
GossenJA
VijgJ
1995 Plasmid-based transgenic mouse model for studying in vivo mutations. Nature 377 657 659
7. VijgJ
DolléME
2002 Large genome rearrangements as a primary cause of aging. Mech Ageing Dev 123 907 915
8. BrittenRJ
1986 Rates of DNA sequence evolution differ between taxonomic groups. Science 231 1393 1398
9. BaerCF
MiyamotoMM
DenverDR
2007 Mutation rate variation in multicellular eukaryotes: causes and consequences. Nat Rev Genet 8 619 631
10. GarciaAM
DerventziA
BusuttilR
CalderRB
PerezEJr
2007 A model system for analyzing somatic mutations in Drosophila melanogaster. Nat Methods 4 401 403
11. GossenJA
de LeeuwWJ
VerwestA
LohmanPH
VijgJ
1991 High somatic mutation frequencies in a LacZ transgene integrated on the mouse X-chromosome. Mutat Res 250 423 429
12. DolléME
SnyderWK
GossenJA
LohmanPH
VijgJ
2000 Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. Proc Natl Acad Sci U S A 97 8403 8408
13. DavidJR
1988 Temperature.
LintsFH
SolimanMH
Drosophila as a Model Organism for Ageing Studies London Blackie 33 45
14. DolléME
VijgJ
2002 Genome dynamics in aging mice. Genome Res 12 1732 1738
15. ElenaSF
LenskiRE
1997 Test of synergistic interactions among deleterious mutations in bacteria. Nature 390 395 398
16. DolleME
MartusHJ
NovakM
van OrsouwNJ
VijgJ
1999 Characterization of color mutants in lacZ plasmid-based transgenic mice, as detected by positive selection. Mutagenesis 14 287 293
17. KeightleyPD
TrivediU
ThomsonM
OliverF
KumarS
2009 Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines. Genome Res 19 1195 1201
18. CrowJF
1997 The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A 94 8380 8386
19. GarciaAM
BusuttilRA
CalderRB
DolleME
DiazV
2008 Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues. Mech Ageing Dev 129 528 533
20. MasoroEJ
2005 Overview of caloric restriction and ageing. Mech Ageing Dev 126 913 922
21. EdmanU
GarciaAM
BusuttilRA
SorensenD
LundellM
2009 Lifespan extension by dietary restriction is not linked to protection against somatic DNA damage in Drosophila melanogaster. Aging Cell 8 331 338
22. MairW
GoymerP
PletcherSD
PartridgeL
2003 Demography of dietary restriction and death in Drosophila. Science 301 1731 1733
23. PiperMD
PartridgeL
2007 Dietary restriction in Drosophila: delayed aging or experimental artefact? PLoS Genet 3 e57 doi:10.1371/journal.pgen.0030057
24. AbeleD
HeiseK
PortnerHO
PuntaruloS
2002 Temperature-dependence of mitochondrial function and production of reactive oxygen species in the intertidal mud clam Mya arenaria. J Exp Biol 205 1831 1841
25. GruberJ
SchafferS
HalliwellB
2008 The mitochondrial free radical theory of ageing–where do we stand? Front Biosci 13 6554 6579
26. GilleJJ
van BerkelCG
JoenjeH
1994 Mutagenicity of metabolic oxygen radicals in mammalian cell cultures. Carcinogenesis 15 2695 2699
27. KappelerM
KranzE
WoolcockK
GeorgievO
SchaffnerW
2008 Drosophila bloom helicase maintains genome integrity by inhibiting recombination between divergent DNA sequences. Nucleic Acids Res 36 6907 6917
28. McVeyM
LarocqueJR
AdamsMD
SekelskyJJ
2004 Formation of deletions during double-strand break repair in Drosophila DmBlm mutants occurs after strand invasion. Proc Natl Acad Sci U S A 101 15694 15699
29. BusuttilRA
GarciaAM
ReddickRL
DolleME
CalderRB
2007 Intra-organ variation in age-related mutation accumulation in the mouse. PLoS ONE 2 e876 doi:10.1371/journal.pone.0000876
30. LevineM
DavidsonEH
2005 Gene regulatory networks for development. Proc Natl Acad Sci U S A 102 4936 4942
31. GarciaAM
BusuttilRA
RodriguezA
CabreraC
LundellM
2007 Detection and analysis of somatic mutations at a lacZ reporter locus in higher organisms: application to Mus musculus and Drosophila melanogaster. Methods Mol Biol 371 267 287
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2010 Číslo 5
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Common Genetic Variants near the Brittle Cornea Syndrome Locus Influence the Blinding Disease Risk Factor Central Corneal Thickness
- All About Mitochondrial Eve: An Interview with Rebecca Cann
- The Relationship among Gene Expression, the Evolution of Gene Dosage, and the Rate of Protein Evolution
- SMA-10/LRIG Is a Conserved Transmembrane Protein that Enhances Bone Morphogenetic Protein Signaling