An Ecologist’s Guide to Mitochondrial DNA Mutations and Senescence

Hood, Wendy R.; Williams, Ashley S; Hill, Geoffrey E.

doi:10.1093/icb/icz097

Cited by 12 publications

(8 citation statements)

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“…There are a number of lines of evidence indicating that the reduced fertility in older females is associated with increasing levels of dysfunction in the mitochondria of their oocytes [46,120,121]. It has been known for a long time that mitochondria 'age' in somatic tissues as a result of a gradual increase over time in levels of oxidative damage to mitochondrial DNA (mtDNA) and mitochondrial membranes [122,123] and mutations in mtDNA due to replication errors [124,125]. Oxidative damage arises as a result of an imbalance between the production of ROS, principally by the mitochondria themselves, and the cell's antioxidant defences [126].…”

Section: (C) Mitochondrial Ageing In the Germlinementioning

confidence: 99%

“…This increase in damage is non-trivial: for example, the level of oxidative damage and the consequent mutation rate of mitochondrial DNA is far higher than that of nuclear DNA, due to mtDNA being positioned very close to the inner mitochondrial membrane (the major source of the ROS) yet lacking the protective histones and DNA repair capacity of nuclear DNA [122,127]. Replication errors also accumulate faster in mtDNA than in nuclear DNA due to the rapid turnover of the mitochondria [124,125]. It is noteworthy that somatic cells lack the means to eliminate most forms of deleterious mtDNA from their tissues [123].…”

Section: (C) Mitochondrial Ageing In the Germlinementioning

confidence: 99%

“…The germline is not entirely protected from ageing of the soma, and is also influenced by senescence of the tissues that maintain the germ-line. The selection pressures affecting age-related germline deterioration are likely to depend on the lifespan of the species, since this will influence for instance whether there has been enough time for sufficient mutations to accumulate to cause dysfunction [124,125]. This raises a number of interesting questions with respect to life-history evolution, particularly for traits such as reproductive scheduling and mating strategies.…”

Section: Implications For Life Historiesmentioning

confidence: 99%

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The deteriorating soma and the indispensable germline: gamete senescence and offspring fitness

2019

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The idea that there is an impenetrable barrier that separates the germline and soma has shaped much thinking in evolutionary biology and in many other disciplines. However, recent research has revealed that the so-called ‘Weismann Barrier’ is leaky, and that information is transferred from soma to germline. Moreover, the germline itself is now known to age, and to be influenced by an age-related deterioration of the soma that houses and protects it. This could reduce the likelihood of successful reproduction by old individuals, but also lead to long-term deleterious consequences for any offspring that they do produce (including a shortened lifespan). Here, we review the evidence from a diverse and multidisciplinary literature for senescence in the germline and its consequences; we also examine the underlying mechanisms responsible, emphasizing changes in mutation rate, telomere loss, and impaired mitochondrial function in gametes. We consider the effect on life-history evolution, particularly reproductive scheduling and mate choice. Throughout, we draw attention to unresolved issues, new questions to consider, and areas where more research is needed. We also highlight the need for a more comparative approach that would reveal the diversity of processes that organisms have evolved to slow or halt age-related germline deterioration.

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Section: (C) Mitochondrial Ageing In the Germlinementioning

confidence: 99%

Section: (C) Mitochondrial Ageing In the Germlinementioning

confidence: 99%

Section: Implications For Life Historiesmentioning

confidence: 99%

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The deteriorating soma and the indispensable germline: gamete senescence and offspring fitness

2019

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“…Perhaps the best‐studied theory for the physiological basis of ageing and senescence is Harman's ‘free radical theory of ageing’, which posits that reactive oxygen species (ROS)‐induced oxidative damage accumulates as animals age and ultimately determines the lifespan of animals (Harman, 1992; Beckman & Ames, 1998; Metcalfe & Alonso‐Alvarez, 2010; Selman et al ., 2012). Since the publication of Harman's seminal paper in Harman, 1992, countless ecological studies have been conducted to evaluate the role of oxidative stress in ageing and senescence, but support for the theory has been equivocal (Selman et al ., 2012; Gladyshev, 2014; Hood, Williams, & Hill, 2019). One key area that has so far been overlooked by the ecology and evolution community is the role of ER stress and UPR ER on ageing and senescence (Pluquet, Pourtier, & Abbadie, 2015).…”

Section: Ageing and Senescencementioning

confidence: 99%

Evaluating endoplasmic reticulum stress and unfolded protein response through the lens of ecology and evolution

et al. 2020

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Considerable progress has been made in understanding the physiological basis for variation in the life‐history patterns of animals, particularly with regard to the roles of oxidative stress and hormonal regulation. However, an underappreciated and understudied area that could play a role in mediating inter‐ and intraspecific variation of life history is endoplasmic reticulum (ER) stress, and the resulting unfolded protein response (UPRER). ER stress response and the UPRER maintain proteostasis in cells by reducing the intracellular load of secretory proteins and enhancing protein folding capacity or initiating apoptosis in cells that cannot recover. Proper modulation of the ER stress response and execution of the UPRER allow animals to respond to intracellular and extracellular stressors and adapt to constantly changing environments. ER stress responses are heritable and there is considerable individual variation in UPRER phenotype in animals, suggesting that ER stress and UPRER phenotype can be subjected to natural selection. The variation in UPRER phenotype presumably reflects the way animals respond to ER stress and environmental challenges. Most of what we know about ER stress and the UPRER in animals has either come from biomedical studies using cell culture or from experiments involving conventional laboratory or agriculturally important models that exhibit limited genetic diversity. Furthermore, these studies involve the assessment of experimentally induced qualitative changes in gene expression as opposed to the quantitative variations that occur in naturally existing populations. Almost all of these studies were conducted in controlled settings that are often quite different from the conditions animals experience in nature. Herein, we review studies that investigated ER stress and the UPRER in relation to key life‐history traits including growth and development, reproduction, bioenergetics and physical performance, and ageing and senescence. We then ask if these studies can inform us about the role of ER stress and the UPRER in mediating the aforementioned life‐history traits in free‐living animals. We propose that there is a need to conduct experiments pertaining to ER stress and the UPRER in ecologically relevant settings, to characterize variation in ER stress and the UPRER in free‐living animals, and to relate the observed variation to key life‐history traits. We urge others to integrate multiple physiological systems and investigate how interactions between ER stress and oxidative stress shape life‐history trade‐offs in free‐living animals.

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“…2005; Szczepanowska and Trifunovic 2015; DeBalsi et al . 2017; Hood et al . 2019).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial mutations inCaenorhabditis elegansshow signatures of oxidative damage and an AT-bias

Waneka

Svendsen

Havird

et al. 2021

Preprint

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Rapid mutation rates are typical of mitochondrial genomes (mtDNAs) in animals, but it is not clear why. The difficulty of obtaining measurements of mtDNA mutation that are not biased by natural selection has stymied efforts to distinguish between competing hypotheses about the causes of high mtDNA mutation rates. Several studies which have measured mtDNA mutations in nematodes have yielded small datasets with conflicting conclusions about the relative abundance of different substitution classes (i.e. the mutation spectrum). We therefore leveraged Duplex Sequencing, a high-fidelity DNA sequencing technique, to characterize de novo mtDNA mutations in Caenorhabditis elegans. This approach detected nearly an order of magnitude more mtDNA mutations than documented in any previous nematode mutation study. Despite an existing extreme AT bias in the C. elegans mtDNA (75.6% AT), we found that a significant majority of mutations increase genomic AT content. Compared to some prior studies in nematodes and other animals, the mutation spectrum reported here contains an abundance of CGAT transversions, supporting the hypothesis that oxidative damage may be a driver of mtDNA mutations in nematodes. Further, we found an excess of GT and CT changes on the coding DNA strand relative to the template strand, consistent with increased exposure to oxidative damage. Analysis of the distribution of mutations across the mtDNA revealed significant variation among protein-coding genes and as well as among neighboring nucleotides. This high-resolution view of mitochondrial mutations in C. elegans highlights the value of this system for understanding relationships among oxidative damage, replication error, and mtDNA mutation.

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An Ecologist’s Guide to Mitochondrial DNA Mutations and Senescence

Cited by 12 publications

References 123 publications

The deteriorating soma and the indispensable germline: gamete senescence and offspring fitness

The deteriorating soma and the indispensable germline: gamete senescence and offspring fitness

Evaluating endoplasmic reticulum stress and unfolded protein response through the lens of ecology and evolution

Mitochondrial mutations inCaenorhabditis elegansshow signatures of oxidative damage and an AT-bias

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