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1.
Genome Res ; 31(9): 1602-1613, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34404692

RESUMO

Important clues about natural selection can be gleaned from discrepancies between the properties of segregating genetic variants and of mutations accumulated experimentally under minimal selection, provided the mutational process is the same in the laboratory as in nature. The base-substitution spectrum differs between C. elegans laboratory mutation accumulation (MA) experiments and the standing site-frequency spectrum, which has been argued to be in part owing to increased oxidative stress in the laboratory environment. Using genome sequence data from C. elegans MA lines carrying a mutation (mev-1) that increases the cellular titer of reactive oxygen species (ROS), leading to increased oxidative stress, we find the base-substitution spectrum is similar between mev-1, its wild-type progenitor (N2), and another set of MA lines derived from a different wild strain (PB306). Conversely, the rate of short insertions is greater in mev-1, consistent with studies in other organisms in which environmental stress increased the rate of insertion-deletion mutations. Further, the mutational properties of mononucleotide repeats in all strains are different from those of nonmononucleotide sequence, both for indels and base-substitutions, and whereas the nonmononucleotide spectra are fairly similar between MA lines and wild isolates, the mononucleotide spectra are very different, with a greater frequency of A:T → T:A transversions and an increased proportion of ±1-bp indels. The discrepancy in mutational spectra between laboratory MA experiments and natural variation is likely owing to a consistent (but unknown) effect of the laboratory environment that manifests itself via different modes of mutability and/or repair at mononucleotide loci.


Assuntos
Caenorhabditis elegans , Laboratórios , Alelos , Animais , Caenorhabditis elegans/genética , Mutação , Estresse Oxidativo/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-27085374

RESUMO

Exposure to trace metals typically causes oxidative stress; these consequences are better-characterized in estuarine and marine species than in freshwater species. How cellular-level responses to metal pollution influence whole-organism and population-level traits is poorly understood. We tested whether exposure to single metals (zinc and cadmium) and to metal mixtures (water in equilibrium with sediment from a highly polluted lake) alters two ecologically-relevant traits in freshwater clams, locomotion and reproduction. Fingernail clams (Musculium spp.) from unimpacted habitats were exposed to single metals and the metal mixture for up to 49days. The single metal doses (≤5mg/L Zn and ≤20µg/L Cd) were not toxicologically meaningful as clam survival, burial, and climbing activity did not differ across treatments. Water in equilibrium with the lake sediment contained cadmium, copper, lead, and zinc. Clams exposed to this metal mixture had decreased climbing activity but no change in burial activity. Metal-exposed clams had lower fecundity (number of shelled juveniles extruded by adult clams) and patterns in metal accumulation corresponded with lake sediment dose and clam activity. In contrast to the functional traits, stress protein expression and whole-clam glycogen content did not vary across treatment groups. These results indicate that fingernail clams of the genus Musculium are appropriate for development as sentinel species for metal pollution and can serve as a model for determining how metal pollution alters metabolic allocation patterns in freshwater organisms.


Assuntos
Biomarcadores/metabolismo , Bivalves/efeitos dos fármacos , Sedimentos Geológicos/química , Metais/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/metabolismo , Bivalves/fisiologia , Cádmio/metabolismo , Cádmio/toxicidade , Chaperonina 60/metabolismo , Cobre/metabolismo , Cobre/toxicidade , Relação Dose-Resposta a Droga , Água Doce/química , Geografia , Glicogênio/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Estimativa de Kaplan-Meier , Larva/efeitos dos fármacos , Larva/metabolismo , Larva/fisiologia , Chumbo/metabolismo , Chumbo/toxicidade , Locomoção/efeitos dos fármacos , Metais/metabolismo , Atividade Motora/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Ubiquitina/metabolismo , Washington , Zinco/metabolismo , Zinco/toxicidade
5.
Evolution ; 69(2): 508-19, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25495240

RESUMO

Understanding the genetic basis of susceptibility to pathogens is an important goal of medicine and of evolutionary biology. A key first step toward understanding the genetics and evolution of any phenotypic trait is characterizing the role of mutation. However, the rate at which mutation introduces genetic variance for pathogen susceptibility in any organism is essentially unknown. Here, we quantify the per-generation input of genetic variance by mutation (VM) for susceptibility of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa (defined as the median time of death, LT50). VM for LT50 is slightly less than VM for a variety of life-history and morphological traits in this strain of C. elegans, but is well within the range of reported values in a variety of organisms. Mean LT50 did not change significantly over 250 generations of mutation accumulation. Comparison of VM to the standing genetic variance (VG) implies a strength of selection against new mutations of a few tenths of a percent. These results suggest that the substantial standing genetic variation for susceptibility of C. elegans to P. aeruginosa can be explained by polygenic mutation coupled with purifying selection.


Assuntos
Caenorhabditis elegans/genética , Caenorhabditis elegans/microbiologia , Variação Genética , Mutação , Infecções por Pseudomonas/genética , Animais , Evolução Biológica , Suscetibilidade a Doenças/microbiologia , Pseudomonas aeruginosa
6.
PLoS One ; 8(6): e65604, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23776511

RESUMO

We explored the relationship between relaxed selection, oxidative stress, and spontaneous mutation in a set of mutation-accumulation (MA) lines of the nematode Caenorhabditis elegans and in their common ancestor. We measured steady-state levels of free radicals and oxidatively damaged guanosine nucleosides in the somatic tissues of five MA lines for which nuclear genome base substitution and GC-TA transversion frequencies are known. The two markers of oxidative stress are highly correlated and are elevated in the MA lines relative to the ancestor; point estimates of the per-generation rate of mutational decay (ΔM) of these measures of oxidative stress are similar to those reported for fitness-related traits. Conversely, there is no significant relationship between either marker of oxidative stress and the per-generation frequencies of base substitution or GC-TA transversion. Although these results provide no direct evidence for a causative relationship between oxidative damage and base substitution mutations, to the extent that oxidative damage may be weakly mutagenic in the germline, the case for condition-dependent mutation is advanced.


Assuntos
Caenorhabditis elegans/metabolismo , Animais , Evolução Biológica , Mutação , Estresse Oxidativo/fisiologia , Seleção Genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-23558301

RESUMO

Aquatic hypoxia is generally viewed as stressful for aerobic organisms. However, hypoxia may also benefit organisms by decreasing cellular stress, particularly that related to free radicals. Thus, an ideal habitat may have the minimum O2 necessary to both sustain aerobic metabolism and reduce the need to scavenge free radicals and repair free radical damage. The ability of aquatic organisms to sustain aerobic metabolism relates in part to the ability to maximize gas diffusion, which can be facilitated by small body size when O2 uptake occurs across the body surface, by a large gill surface area, or by the ability to use atmospheric air. We use water-breathing organisms in chronically hypoxic papyrus (Cyperus papyrus) swamps of East Africa to test the hypothesis that cellular-level benefits of hypoxia may translate into increased fitness, especially for small organisms. A review of recent studies of fingernail clams (Sphaerium sp.) shows that clams living in sustained hypoxia have minimized oxidative stress and that these cellular-level benefits may lead to increased fitness. We suggest that organisms in the extreme conditions in the papyrus swamps provide a unique opportunity to challenge the conventional classification of hypoxic habitats as 'stressful' and normoxic habitats as 'optimal.'


Assuntos
Peixes/fisiologia , Aptidão Genética , Estresse Oxidativo , Oxigênio/metabolismo , Animais , Água Doce , Brânquias/fisiologia , Hidrobiologia , Hipóxia , Áreas Alagadas
9.
Genetics ; 189(4): 1439-47, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21979932

RESUMO

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.


Assuntos
Caenorhabditis elegans/genética , Mutação em Linhagem Germinativa , Estresse Oxidativo , Animais
10.
Evolution ; 64(11): 3242-53, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20649813

RESUMO

Evolutionary theory predicts that the strength of natural selection to reduce the mutation rate should be stronger in self-fertilizing than in outcrossing taxa. However, the relative efficacy of selection on mutation rate relative to the many other factors influencing the evolution of any species is poorly understood. To address this question, we allowed mutations to accumulate for ∼100 generations in several sets of "mutation accumulation" (MA) lines in three species of gonochoristic (dieocious) Caenorhabditis (C. remanei, C. brenneri, C. sp. 5) as well as in a dioecious strain of the historically self-fertile hermaprohodite C. elegans. In every case, the rate of mutational decay is substantially greater in the gonochoristic taxa than in C. elegans (∼4× greater on average). Residual heterozygosity in the ancestral controls of these MA lines introduces some complications in interpreting the results, but circumstantial evidence suggests the results are not primarily due to inbreeding depression resulting from residual segregating variation. The results suggest that natural selection operates to optimize the mutation rate in Caenorhabditis and that the strength (or efficiency) of selection differs consistently on the basis of mating system, as predicted by theory. However, context-dependent environmental and/or synergistic epistasis could also explain the results.


Assuntos
Caenorhabditis/genética , Cruzamentos Genéticos , Mutação , Animais , Análise Mutacional de DNA , Evolução Molecular , Feminino , Variação Genética , Heterozigoto , Masculino , Modelos Genéticos , Reprodução , Seleção Genética , Comportamento Sexual Animal , Especificidade da Espécie
11.
Physiol Biochem Zool ; 83(2): 356-65, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19327040

RESUMO

Hydrogen sulfide acts as an environmental toxin across a range of concentrations and as a cellular signaling molecule at very low concentrations. Despite its toxicity, many animals, including the mudflat polychaete Glycera dibranchiata, are periodically or continuously exposed to sulfide in their environment. We tested the hypothesis that a broad range of ecologically relevant sulfide concentrations induces oxidative stress and oxidative damage to RNA and DNA in G. dibranchiata. Coelomocytes exposed in vitro to sulfide (0-3 mmol L(-1) for 1 h) showed dose-dependent increases in oxidative stress (as 2',7'-dichlorofluorescein fluorescence) and superoxide production (as dihydroethidine fluorescence). Coelomocytes exposed in vitro to sulfide (up to 0.73 mmol L(-1) for 2 h) also acquired increased oxidative damage to RNA (detected as 8-oxo-7,8-dihydroguanosine) and DNA (detected as 8-oxo-7,8-dihydro-2'-deoxyguanosine). Worms exposed in vivo to sulfide (0-10 mmol L(-1) for 24 h) acquired elevated oxidative damage to RNA and DNA in both coelomocytes and body wall tissue. While the consequences of RNA and DNA oxidative damage are poorly understood, oxidatively damaged deoxyguanosine bases preferentially bind thymine, causing G-T transversions and potentially causing heritable point mutations. This suggests that sulfide can be an environmental mutagen in sulfide-tolerant invertebrates.


Assuntos
Dano ao DNA/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Poliquetos/fisiologia , RNA/efeitos dos fármacos , Animais , DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Mutação Puntual/efeitos dos fármacos , Poliquetos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
12.
J Aquat Anim Health ; 21(2): 104-16, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19873832

RESUMO

An understanding of the complex effects of the environment on biomarkers of bivalve health is essential for aquaculturists to successfully select field culture sites and monitor bivalve health in these sites and in hatcheries. We tested several whole-organism (functional) and cellular-level biomarkers as indicators of health of the cultured, stress-tolerant northern quahog (hard clam) Mercenaria mercenaria. We performed single- and dual-stressor experiments that were consistent with available water quality data from a clam culture area on the Gulf coast of Florida. Clams from the culture area were exposed over a 14-d period to low O2 (hypoxia), elevated temperature, hyposalinity, and a combination of elevated temperature and hyposalinity. There was no clear relationship between the functional and cellular-level biomarkers, with most of the treatment effects being detected at the whole-organism level but not the cellular level. Survival and burial ability were significantly affected by elevated temperature and by the combination of elevated temperature and hyposalinity. Glycogen content decreased over the experiment duration and did not differ significantly among treatments. There were no significant changes in expression patterns of eight stress proteins or in the levels of oxidatively damaged RNA. The results highlight the importance of investigating the effects of multiple stressors in short-term, controlled laboratory conditions and suggest that such cellular-level biomarker assays should be paired with functional biomarkers to better understand the responses of highly stress-tolerant species.


Assuntos
Mercenaria/efeitos dos fármacos , Mercenaria/metabolismo , Estresse Fisiológico , Animais , Biomarcadores , Relação Dose-Resposta a Droga , Ecossistema , Monitoramento Ambiental , Regulação da Expressão Gênica , Glicogênio/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Oxirredução , Oxigênio/farmacologia , RNA/genética , RNA/metabolismo , Cloreto de Sódio/farmacologia , Temperatura
13.
J Gerontol A Biol Sci Med Sci ; 64(11): 1134-45, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19671885

RESUMO

The evolutionary mechanisms maintaining genetic variation in life span, particularly post-reproductive life span, are poorly understood. We characterized the effects of spontaneous mutations on life span in the rhabditid nematodes Caenorhabditis elegans and C. briggsae and standing genetic variance for life span and correlation of life span with fitness in C. briggsae. Mutations decreased mean life span, a signature of directional selection. Mutational correlations between life span and fitness were consistently positive. The average selection coefficient against new mutations in C. briggsae was approximately 2% when homozygous. The pattern of phylogeographic variation in life span is inconsistent with global mutation-selection balance (MSB), but MSB appears to hold at the local level. Standing genetic correlations in C. briggsae reflect mutational correlations at a local scale but not at a broad phylogeographic level. At the local scale, results are broadly consistent with predictions of the "mutation accumulation" hypothesis for the evolution of aging.


Assuntos
Envelhecimento/genética , Caenorhabditis/genética , Variação Genética , Mutação , Seleção Genética , Animais , Caenorhabditis elegans/genética , Mortalidade
14.
Artigo em Inglês | MEDLINE | ID: mdl-16890466

RESUMO

Endogenous free radical production and resulting oxidative damage may result from exposure to hypoxia, hyperoxia, or hydrogen sulfide. Previous investigations of sulfide-induced oxidative damage have produced conflicting results, perhaps because these studies utilized species presumably adapted to sulfide. We examined the effects of sulfide, hypoxia and hyperoxia on the surf clam Donax variabilis to test whether these stressors induce a cellular response to oxidative stress. These clams inhabit high-energy sandy beaches and are unlikely to have specific adaptations to these stressors. In duplicate flow-through experiments performed in fall and spring, clams were exposed to normoxia (22 kPa P(O(2))), hypoxia (10 kPa), hyperoxia (37 kPa), or sulfide with normoxia ( approximately 100 mumol L(-1), 22 kPa respectively) for 24 h. We quantified whole-animal expression of three antioxidants (Cu/Zn and Mn superoxide dismutases, glutathione peroxidase), a lipid peroxidation marker (4-hydroxy-2E-nonenol-adducted protein), a DNA repair enzyme (OGG1-m), four heat shock proteins (small Hsp, Hsp60, Hsp70, and mitochondrial Hsp70), ubiquitin, and actin. Clams exposed to sulfide showed upregulation of the greatest number of stress proteins and the pattern was consistent with a cellular response to oxidative stress. Furthermore, there was a marked seasonality, with greater stress protein expression in clams from the spring.


Assuntos
Bivalves/metabolismo , Sulfeto de Hidrogênio/farmacologia , Actinas/biossíntese , Aldeídos/metabolismo , Animais , Antioxidantes/metabolismo , Bivalves/efeitos dos fármacos , DNA Glicosilases/biossíntese , Glutationa Peroxidase/biossíntese , Proteínas de Choque Térmico/biossíntese , Proteínas de Choque Térmico/metabolismo , Hiperóxia/fisiopatologia , Hipóxia/fisiopatologia , Peroxidação de Lipídeos/fisiologia , Estações do Ano , Superóxido Dismutase/biossíntese , Ubiquitina/biossíntese , Regulação para Cima
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