Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

Garcı́a, Ana Maria; Calder, R. Brent; Dollé, Martijn E.T.; Lundell, Martha J.; Kapahi, Pankaj; Vijg, Jan

doi:10.1371/journal.pgen.1000950

Cited by 64 publications

(58 citation statements)

References 32 publications

(43 reference statements)

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“…First, there may be a class of mutations of large effect that occurs more frequently in mev-1 than in N2 but that is still relatively rare. For example, the post-mitotic tissues of aging mice (Dollé et al 2000) and fruit flies (Garcia et al 2010) have high incidences of large genome rearrangements and relatively few 1-bp deletions and GC-AT mutations, spectra that may be consistent with elevated oxidative stress (Gille and Van Berkel 1994;Melov et al 1995;Busuttil et al 2007). It is possible that large genome rearrangements could have contributed to the high extinction rates in the mev-1 MA lines.…”

Section: Discussionmentioning

confidence: 99%

No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

et al. 2011

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Variation in rates of molecular evolution has been attributed to numerous, interrelated causes, including metabolic rate, body size, and generation time. Speculation concerning the influence of metabolic rate on rates of evolution often invokes the putative mutagenic effects of oxidative stress. To isolate the effects of oxidative stress on the germline from the effects of metabolic rate, generation time, and other factors, we allowed mutations to accumulate under relaxed selection for 125 generations in two strains of the nematode Caenorhabditis elegans, the canonical wild-type strain (N2) and a mutant strain with elevated steady-state oxidative stress (mev-1). Contrary to our expectation, the mutational decline in fitness did not differ between N2 and mev-1. This result suggests that the mutagenic effects of oxidative stress in C. elegans are minor relative to the effects of other types of mutations, such as errors during DNA replication. However, mev-1 MA lines did go extinct more frequently than wild-type lines; some possible explanations for the difference in extinction rate are discussed. Lanfear et al. 2007;and Galtier et al. 2009). Usually, it is supposed that organisms with high metabolic rates have higher rates of mutation, and thus faster rates of evolution, than do organisms with low metabolic rates. There are two (not mutually exclusive) ways by which metabolic rate might affect mutation rate. First, organisms with high metabolic rates have shorter generation times (Savage et al. 2004;Bromham 2009) and thus undergo relatively more rounds of DNA replication per generation (Laird et al. 1969;Ellegren 2007;Nikolaev et al. 2007;Thomas et al. 2010) than do organisms with low metabolic rates. If most mutations occur during DNA replication, a positive relationship between metabolic rate and mutation rate, and thus rates of evolution, is expected. Second, the oxygen-centered free radicals that are by-products of aerobic metabolism (Boveris and Chance 1973;Fridovich 2004) can cause oxidative damage to DNA (Hsie et al.

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Section: Discussionmentioning

confidence: 99%

No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

et al. 2011

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“…Interestingly, the results obtained when comparing the two models indicate a threefold higher spontaneous mutation frequency in flies than in mice [39] . Also the fraction of genome rearrangements in flies was found to be much larger than in mice [39] . In these assays the mutation frequency is determined per locus, as the number of mutated transgenes versus the total number of transgenes recovered from a DNA sample.…”

Section: Measuring Small Mutationsmentioning

confidence: 96%

Measuring Genome Instability in Aging – A Mini-Review

Vijg²

2011

Gerontology

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Background: There is mounting evidence for an age-dependent accumulation of somatic mutations as a result of the inherent imperfection of DNA replication and repair. A possible age-related decline in genome maintenance systems may exacerbate this age-related loss of genome integrity. A review of the current methods of mutation detection is timely in view of the lack of insight as to the magnitude of somatic mutation accumulation, the types of mutations that accumulate, and their functional consequences. Objective: In this paper we review the current methods for measuring genome instability in organisms during aging or in relation to life span. Methods: The review is based on established and novel concepts from the existing literature, with some examples from our own laboratory. Results: Studies using cytogenetic assays and endogenous or transgenic mutation reporter assays provide strong evidence for age-related increases of different types of mutations in animals and humans during aging. This increase in DNA mutations is tissue-specific and also differs between species. Conclusion: Today, our knowledge of somatic mutation profiles in aging is mainly derived from cytogenetics and the use of endogenous and transgenic mutation reporter assays. The emergence of new approaches, most notably massively parallel sequencing, will give us deeper insight into the nature of spontaneous genome instability and its possible causal relationship to aging and age-related disease.

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“…Studies on Drosophila melanogaster suggest that indeed temperature-dependent metabolic activities increased the somatic mutation rate as consequence of oxidative stress [62]. However, temperature had no influence on the transposition rate in the same species [63,64].…”

Section: (D) Mutation Ratementioning

confidence: 97%

Support for the evolutionary speed hypothesis from intraspecific population genetic data in the non-biting midgeChironomus riparius

et al. 2016

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The evolutionary speed hypothesis (ESH) proposes a causal mechanism for the latitudinal diversity gradient. The central idea of the ESH is that warmer temperatures lead to shorter generation times and increased mutation rates. On an absolute time scale, both should lead to an acceleration of selection and drift. Based on the ESH, we developed predictions regarding the distribution of intraspecific genetic diversity: populations of ectothermic species with more generations per year owing to warmer ambient temperatures should be more differentiated from each other, accumulate more mutations and show evidence for increased mutation rates compared with populations in colder regions. We used the multivoltine insect species Chironomus riparius to test these predictions with cytochrome oxidase I (COI) sequence data and found that populations from warmer regions are indeed significantly more differentiated and have significantly more derived haplotypes than populations from colder regions. We also found a significant correlation of the annual mean temperature with the population mutation parameter u that serves as a proxy for the per generation mutation rate under certain assumptions. This pattern could be corroborated with two nuclear loci. Overall, our results support the ESH and indicate that the thermal regime experienced may be crucially driving the evolution of ectotherms and may thus ultimately govern their speciation rate.

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Age- and Temperature-Dependent Somatic Mutation Accumulation in Drosophila melanogaster

Cited by 64 publications

References 32 publications

No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

Measuring Genome Instability in Aging – A Mini-Review

Support for the evolutionary speed hypothesis from intraspecific population genetic data in the non-biting midgeChironomus riparius

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