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1.
Mol Ecol Resour ; 20(1): 308-317, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31660689

RESUMO

Reptiles and other nonmammalian vertebrates have transcriptionally active nucleated red blood cells. If blood transcriptomes can provide quantitative data to address questions relevant to molecular ecology, this could circumvent the need to euthanize animals to assay tissues. This would allow longitudinal sampling of animals' responses to treatments, as well as sampling of protected taxa. We developed and annotated blood transcriptomes from six reptile species and found on average 25,000 proteins are being transcribed in the blood, and there is a CORE group of 9,282 orthogroups that are found in at least four of six species. In comparison to liver transcriptomes from the same taxa, approximately two-thirds of the orthogroups were found in both blood and liver; and a similar percentage of ecologically relevant gene groups (insulin and insulin-like signalling, electron transport chain, oxidative stress, glucocorticoid receptors) were found transcribed in both blood and liver. As a resource, we provide a user-friendly database of gene ids identified in each blood transcriptome. Although on average 37% of reads mapped to haemoglobin, importantly, the majority of nonhaemoglobin transcripts had sufficient depth (e.g., 97% at ≥10 reads) to be included in differential gene expression analysis. Thus, we demonstrate that RNAseq blood transcriptomes from a very small blood sample (<10 µl) is a minimally invasive option in nonmammalian vertebrates for quantifying expression of a large number of ecologically relevant genes that would allow longitudinal sampling and sampling of protected populations.

2.
Am J Physiol Cell Physiol ; 317(6): C1313-C1323, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618076

RESUMO

Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported that skeletal muscle L1 expression is lower following acute and chronic exercise training in humans. Herein, we used a rodent model of voluntary wheel running to determine whether long-term exercise training affects markers of skeletal muscle L1 regulation. Selectively bred high-running female Wistar rats (n = 11 per group) were either given access to a running wheel (EX) or not (SED) at 5 wk of age, and these conditions were maintained until 27 wk of age. Thereafter, mixed gastrocnemius tissue was harvested and analyzed for L1 mRNA expression and DNA content along with other L1 regulation markers. We observed significantly (P < 0.05) lower L1 mRNA expression, higher L1 DNA methylation, and less L1 DNA in accessible chromatin regions in EX versus SED rats. We followed these experiments with 3-h in vitro drug treatments in L6 myotubes to mimic transient exercise-specific signaling events. The AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR; 4 mM) significantly decreased L1 mRNA expression in L6 myotubes. However, this effect was not facilitated through increased L1 DNA methylation. Collectively, these data suggest that long-term voluntary wheel running downregulates skeletal muscle L1 mRNA, and this may occur through chromatin modifications. Enhanced AMPK signaling with repetitive exercise bouts may also decrease L1 mRNA expression, although the mechanism of action remains unknown.

3.
Mol Ecol ; 28(18): 4135-4137, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31559659

RESUMO

Flies-a small name for an enormous taxonomic group of over 110,000 described species that have unique ecological roles. Nonbiting flies ingest organic material in faecal matter or carrion, which is rich in microbes and nutrients that benefit both adults and their offspring (maggots). These are often referred to as "filth flies" because they are often pests in human settlements and responsible for the spread of enteric pathogens. Filth flies associate with human populations; however, whether this association is simply due to the presence of organic waste produced, or if flies move with social groups remains unknown. In this issue of Molecular Ecology, Gogarten et al. (2019) use a unique combination of field methods and molecular tools to show that filth flies (predominantly Muscidae [house flies] and Calliphoridae [blow flies]) associate and move with social nonhuman primate (NHP) groups (mangabeys and chimpanzees) for up to 12 days and over 1 km. Filth flies captured near these groups were found to have pathogen DNA on them from the causative agents of sylvatic anthrax and yaws. Furthermore, the authors were able to show that the anthrax bacteria on the flies was viable. Previous research emphasized sylvatic anthrax as a major conservation threat to wildlife at this field site (Hoffmann et al., 2017), highlighting the significance of filth flies as potential vectors of anthrax. The authors present a suite of methods and approaches that utilize flies to better understand rainforest biodiversity, pathogen transmission potential, and filth fly-host associations. This work represents new directions and opportunities to integrate entomology into field research and exploit the natural history of flies to understand the pathogen landscape and address outstanding questions in ecology and evolution.

4.
Trends Parasitol ; 35(6): 399-408, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31053334

RESUMO

Global habitat fragmentation is associated with the emergence of infectious diseases of wildlife origins in human populations. Despite this well-accepted narrative, the underlying mechanisms driving this association remain unclear. We introduce a nuanced hypothesis, the 'coevolution effect'. The central concept is that the subdivision of host populations which occurs with habitat fragmentation causes localized coevolution of hosts, obligate parasites, and pathogens which act as 'coevolutionary engines' within each fragment, accelerating pathogen diversification, and increasing pathogen diversity across the landscape. When combined with a mechanism to exit a fragment (e.g., mosquitoes), pathogen variants will spill over into human communities. Through this combined ecoevolutionary approach we may be able to understand the fine-scale mechanisms that drive disease emergence in the Anthropocene.

5.
Integr Comp Biol ; 59(2): 292-305, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31127305

RESUMO

It is frequently hypothesized that animals employ a generalized "stress response," largely mediated by glucocorticoid (GC) hormones, such as corticosterone, to combat challenging environmental conditions. Under this hypothesis, diverse stressors are predicted to have concordant effects across biological levels of an organism. We tested the generalized stress response hypothesis in two complementary experiments with juvenile and adult male Eastern fence lizards (Sceloporus undulatus). In both experiments, animals were exposed to diverse, ecologically-relevant, acute stressors (high temperature or red imported fire ants, Solenopsis invicta) and we examined their responses at three biological levels: behavioral; physiological (endocrine [plasma corticosterone and blood glucose concentrations] and innate immunity [complement and natural antibodies]); and cellular responses (gene expression of a panel of five heat-shock proteins in blood and liver) at 30 or 90 min post stress initiation. In both experiments, we observed large differences in the cellular response to the two stressors, which contrasts the similar behavioral and endocrine responses. In the adult experiment for which we had innate immune data, the stressors affected immune function independently, and they were correlated with CORT in opposing directions. Taken together, these results challenge the concept of a generalized stress response. Rather, the stress response was context specific, especially at the cellular level. Such context-specificity might explain why attempts to link GC hormones with life history and fitness have proved difficult. Our results emphasize the need for indicators at multiple biological levels and whole-organism examinations of stress.


Assuntos
Formigas , Comportamento Animal/fisiologia , Expressão Gênica/fisiologia , Temperatura Alta/efeitos adversos , Lagartos/fisiologia , Estresse Fisiológico/fisiologia , Animais , Glicemia/metabolismo , Corticosterona/sangue , Proteínas de Choque Térmico/sangue , Proteínas de Choque Térmico/metabolismo , Imunidade Inata/fisiologia , Masculino , Estresse Fisiológico/genética , Estresse Fisiológico/imunologia , Fatores de Tempo
6.
Biol Lett ; 15(2): 20190030, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30958138

RESUMO

Behavioural ecologists often use data on patterns of male-female association to infer reproductive success of free-ranging animals. For example, a male seen with several females during the mating season is predicted to father more offspring than a male not seen with any females. We explored the putative correlation between this behaviour and actual paternity (as revealed by microsatellite data) from a long-term study on sand lizards ( Lacerta agilis), including behavioural observations of 574 adult males and 289 adult females, and paternity assignment of more than 2500 offspring during 1998-2007. The number of males that contributed paternity to a female's clutch was correlated with the number of males seen accompanying her in the field, but not with the number of copulation scars on her body. The number of females that a male accompanied in the field predicted the number of females with whom he fathered offspring, and his annual reproductive success (number of progeny). Although behavioural data explained less than one-third of total variance in reproductive success, our analysis supports the utility of behavioural-ecology studies for predicting paternity in free-ranging reptiles.


Assuntos
Lagartos , Animais , Técnicas de Observação do Comportamento , Feminino , Masculino , Paternidade , Reprodução , Comportamento Sexual Animal
7.
Genome Biol Evol ; 11(3): 629-643, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668691

RESUMO

Cancer is a threat to multicellular organisms, yet the molecular evolution of pathways that prevent the accumulation of genetic damage has been largely unexplored. The p53 network regulates how cells respond to DNA-damaging stressors. We know little about p53 network molecular evolution as a whole. In this study, we performed comparative genetic analyses of the p53 network to quantify the number of genes within the network that are rapidly evolving and constrained, and the association between lifespan and the patterns of evolution. Based on our previous published data set, we used genomes and transcriptomes of 34 sauropsids and 32 mammals to analyze the molecular evolution of 45 genes within the p53 network. We found that genes in the network exhibited evidence of positive selection and divergent molecular evolution in mammals and sauropsids. Specifically, we found more evidence of positive selection in sauropsids than mammals, indicating that sauropsids have different targets of selection. In sauropsids, more genes upstream in the network exhibited positive selection, and this observation is driven by positive selection in squamates, which is consistent with previous work showing rapid divergence and adaptation of metabolic and stress pathways in this group. Finally, we identified a negative correlation between maximum lifespan and the number of genes with evidence of divergent molecular evolution, indicating that species with longer lifespans likely experienced less variation in selection across the network. In summary, our study offers evidence that comparative genomic approaches can provide insights into how molecular networks have evolved across diverse species.


Assuntos
Evolução Molecular , Genes p53 , Seleção Genética , Vertebrados/genética , Animais , Filogenia
8.
Ecol Evol ; 8(12): 6169-6182, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29988440

RESUMO

Many oceanic islands harbor diverse species that differ markedly from their mainland relatives with respect to morphology, behavior, and physiology. A particularly common morphological change exhibited by a wide range of species on islands worldwide involves either a reduction in body size, termed island dwarfism, or an increase in body size, termed island gigantism. While numerous instances of dwarfism and gigantism have been well documented, documentation of other morphological changes on islands remains limited. Furthermore, we lack a basic understanding of the physiological mechanisms that underlie these changes, and whether they are convergent. A major hypothesis for the repeated evolution of dwarfism posits selection for smaller, more efficient body sizes in the context of low resource availability. Under this hypothesis, we would expect the physiological mechanisms known to be downregulated in model organisms exhibiting small body sizes due to dietary restriction or artificial selection would also be downregulated in wild species exhibiting dwarfism on islands. We measured body size, relative head size, and circulating blood glucose in three species of reptiles-two snakes and one lizard-in the California Channel Islands relative to mainland populations. Collating data from 6 years of study, we found that relative to mainland population the island populations had smaller body size (i.e., island dwarfism), smaller head sizes relative to body size, and lower levels of blood glucose, although with some variation by sex and year. These findings suggest that the island populations of these three species have independently evolved convergent physiological changes (lower glucose set point) corresponding to convergent changes in morphology that are consistent with a scenario of reduced resource availability and/or changes in prey size on the islands. This provides a powerful system to further investigate ecological, physiological, and genetic variables to elucidate the mechanisms underlying convergent changes in life history on islands.

9.
Obesity (Silver Spring) ; 26(4): 723-729, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29476611

RESUMO

OBJECTIVE: Prior work concerning maternal perception of the food environment suggests that perceived disparities in food resources resulted in reduced pup mass and dam reproductive success. This study attempted to replicate this result with increased sample size and additional measures. METHODS: Female C57BL/6J mice (n = 160; 3 weeks old) were randomly assigned to either subject or peer and were pair housed in partitioned cages with olfactory and visual contact. After a 6-week maturation period on an energy-rich cafeteria diet, cages were randomly assigned to Control (subject and peer fed pelleted diet) or Treatment (subject fed pellets, peer fed cafeteria diet), and subjects were bred. After weaning, one pup from each sex per litter was reared to 5 months. RESULTS: Treatment did not affect the number of births, pup size at birth, or the proportion of pups surviving to weaning (P > 0.09). Treatment did not affect dam body or fat mass at parturition (P > 0.22), but these measures were higher in some Treatment dams at weaning (P < 0.05). Smaller female pups were weaned from Treatment dams pregnant on the first breeding attempt (P = 0.01), but no other pup effects were observed (P > 0.07). CONCLUSIONS: Exposure to food-environment disparity in this study did not replicate previous findings or affect pup growth after weaning.


Assuntos
Alimentos/normas , Reprodução/fisiologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Percepção , Gravidez , Desmame
10.
Reprod Toxicol ; 75: 1-9, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29128604

RESUMO

Selenium deficiency and toxicity increase the risk of adverse developmental and reproductive outcomes; however, few multi-stressor studies have evaluated the influence of maternal age on organic selenium dose-response and additional stressors over the life course. While multi-stressor research in mammalian models is time-consuming and expensive, use of alternative models can efficiently produce screening data for prioritizing research in mammalian systems. As a well-known eco-toxicological model, Daphnia pulex, may offer advantages in screening for impacts of multi-stressor exposures. We evaluated the influence of maternal age on the effects of seleno-methionine (SeMet) for lifespan, reproduction, and heat-stress resistance in D. pulex. Our results show effects of SeMet-treatment and maternal age, where the highest SeMet-treatment had reduced lifespan and absence of reproduction, and where Daphnia from late life broods had increased resistance to heat-induced stress. Further analysis suggests an additional interactive effect between maternal age and SeMet treatment on time to first reproduction.


Assuntos
Daphnia/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Idade Materna , Selenometionina/farmacologia , Animais , Daphnia/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Reprodução/efeitos dos fármacos , Selenometionina/toxicidade
11.
Biol Lett ; 13(1)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28052937

RESUMO

Endothermy is an evolutionary innovation in eutherian mammals and birds. In eutherian mammals, UCP1 is a key protein in adaptive nonshivering thermogenesis (NST). Although ucp1 arose early in the vertebrate lineage, the loss of ucp1 was previously documented in several reptile species (including birds). Here we determine that ucp1 was lost at the base of the reptile lineage, as we fail to find ucp1 in every major reptile lineage. Furthermore, though UCP1 plays a key role in mammalian NST, we confirm that pig has lost several exons from ucp1 and conclude that pig is not a sole outlier as the only eutherian mammal lineage to do so. Through similarity searches and synteny analysis, we show that ucp1 has also been lost/pseudogenized in Delphinidae (dolphin, orca) and potentially Xenarthra (sloth, armadillo) and Afrotheria (hyrax). These lineages provide models for investigating alternate mechanisms of thermoregulation and energy metabolism in the absence of functional UCP1. Further, the repeated losses of a functional UCP1 suggest the pervasiveness of NST via UCP1 across the mammalian lineage needs re-evaluation.


Assuntos
Evolução Biológica , Aves/genética , Mamíferos/genética , Répteis/genética , Proteína Desacopladora 1/genética , Animais , Filogenia , Termogênese/genética
12.
Exp Gerontol ; 86: 62-72, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27364192

RESUMO

Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reproduction will come with a cost of shortened lifespan; and (3) at a given food concentration, relative to a metabolically equivalent constant temperature environment a diel fluctuating thermal environment will alter the allocation of energy to reproduction and lifespan to maintain homeostasis. We did not identify a level of food concentration that extended lifespan in response to caloric restriction, and we found no cost of reproduction in terms of lifespan. Rather, the individuals at the highest food levels generally had the highest reproductive output and the longest lifespans, the individuals at the intermediate food level decreased reproduction and maintained lifespan, and the individuals at the three lower food concentrations had a decrease in reproduction and lifespan as would be predicted with increasing levels of starvation. Fluctuating temperature had no effect on lifespan at any food concentration, but delayed time to reproductive maturity and decreased early reproductive output at all food concentrations. This suggests that a fluctuating temperature regimen activates molecular pathways that alter energy allocation. The costs of fluctuating temperature on reproduction were not consistent across the lifespan. Statistical interactions for age of peak reproduction and lifetime fecundity suggest that senescence of the reproductive system may vary between temperature regimens at the different food concentrations.


Assuntos
Envelhecimento/fisiologia , Alimentos , Longevidade/fisiologia , Reprodução/fisiologia , Temperatura Ambiente , Animais , Restrição Calórica , Daphnia/fisiologia , Metabolismo Energético/fisiologia , Fertilidade/fisiologia , Taxa de Sobrevida
13.
Integr Comp Biol ; 56(2): 171-84, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27252221

RESUMO

The insulin and insulin-like signaling (IIS) molecular network regulates cellular growth and division, and influences organismal metabolism, growth and development, reproduction, and lifespan. As a group, reptiles have incredible diversity in the complex life history traits that have been associated with the IIS network, yet the research on the IIS network in ectothermic reptiles is sparse. Here, we review the IIS network and synthesize what is known about the function and evolution of the IIS network in ectothermic reptiles. The primary hormones of this network-the insulin-like growth factors 1 and 2 (IGFs) likely function in reproduction in ectothermic reptiles, but the precise mechanisms are unclear, and likely range from influencing mating and ovulation to maternal investment in embryonic development. In general, plasma levels of IGF1 increase with food intake in ectothermic reptiles, but the magnitude of the response to food varies across species or populations and the ages of animals. Long-term temperature treatments as well as thermal stress can alter expression of genes within the IIS network. Although relatively little work has been done on IGF2 in ectothermic reptiles, IGF2 is consistently expressed at higher levels than IGF1 in juvenile ectothermic reptiles. Furthermore, in contrast to mammals that have genetic imprinting that silences the maternal IGF2 allele, in reptiles IGF2 is bi-allelically expressed (based on findings in chickens, a snake, and a lizard). Evolutionary analyses indicate some members of the IIS network are rapidly evolving across reptile species, including IGF1, insulin (INS), and their receptors. In particular, IGF1 displays extensive nucleotide variation across lizards and snakes, which suggests that its functional role may vary across this group. In addition, genetic variation across families and populations in the response of the IIS network to environmental conditions illustrates that components of this network may be evolving in natural populations. The diversity in reproductive physiology, metabolic plasticity, and lifespan among reptiles makes the study of the IIS network in this group a potentially rich avenue for insight into the evolution and function of this network. The field would benefit from future studies that discern the respective functions of IGF1 and IGF2 and how these functions vary across taxa, perfecting additional assays for measuring IIS components, and determining the role of IIS in different tissues.


Assuntos
Insulina/fisiologia , Répteis/fisiologia , Proteínas de Répteis/fisiologia , Transdução de Sinais , Somatomedinas/fisiologia , Animais
14.
Gen Comp Endocrinol ; 233: 88-99, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27181752

RESUMO

The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast-living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs.


Assuntos
Colubridae , Patrimônio Genético , Estágios do Ciclo de Vida/fisiologia , Temperatura Ambiente , Animais , Evolução Biológica , California , Colubridae/genética , Colubridae/crescimento & desenvolvimento , Colubridae/metabolismo , Ecossistema , Ecótipo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Reprodução/fisiologia , Transdução de Sinais/genética
15.
Exp Gerontol ; 71: 135-46, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26403677

RESUMO

Mitochondrial function has long been hypothesized to be intimately involved in aging processes--either directly through declining efficiency of mitochondrial respiration and ATP production with advancing age, or indirectly, e.g., through increased mitochondrial production of damaging free radicals with age. Yet we lack a comprehensive understanding of the evolution of mitochondrial genotypes and phenotypes across diverse animal models, particularly in species that have extremely labile physiology. Here, we measure mitochondrial genome-types and transcription in ecotypes of garter snakes (Thamnophis elegans) that are adapted to disparate habitats and have diverged in aging rates and lifespans despite residing in close proximity. Using two RNA-seq datasets, we (1) reconstruct the garter snake mitochondrial genome sequence and bioinformatically identify regulatory elements, (2) test for divergence of mitochondrial gene expression between the ecotypes and in response to heat stress, and (3) test for sequence divergence in mitochondrial protein-coding regions in these slow-aging (SA) and fast-aging (FA) naturally occurring ecotypes. At the nucleotide sequence level, we confirmed two (duplicated) mitochondrial control regions one of which contains a glucocorticoid response element (GRE). Gene expression of protein-coding genes was higher in FA snakes relative to SA snakes for most genes, but was neither affected by heat stress nor an interaction between heat stress and ecotype. SA and FA ecotypes had unique mitochondrial haplotypes with amino acid substitutions in both CYTB and ND5. The CYTB amino acid change (Isoleucine → Threonine) was highly segregated between ecotypes. This divergence of mitochondrial haplotypes between SA and FA snakes contrasts with nuclear gene-flow estimates, but correlates with previously reported divergence in mitochondrial function (mitochondrial oxygen consumption, ATP production, and reactive oxygen species consequences).


Assuntos
Envelhecimento/fisiologia , Colubridae/fisiologia , Mitocôndrias/fisiologia , Envelhecimento/genética , Animais , Sequência de Bases , Colubridae/genética , Ecótipo , Feminino , Regulação da Expressão Gênica/fisiologia , Redes Reguladoras de Genes/fisiologia , Genoma Mitocondrial , Haplótipos , Resposta ao Choque Térmico/genética , Longevidade/genética , Longevidade/fisiologia , Fenótipo , Alinhamento de Sequência , Especificidade da Espécie
16.
Proc Natl Acad Sci U S A ; 112(22): 7055-60, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-25991861

RESUMO

The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network regulates lifespan and reproduction, as well as metabolic diseases, cancer, and aging. Despite its vital role in health, comparative analyses of IIS/TOR have been limited to invertebrates and mammals. We conducted an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes with 18 newly generated transcriptomes from nonavian reptiles and additional available genomes/transcriptomes. We uncovered rapid and extensive molecular evolution between reptiles (including birds) and mammals: (i) the IIS/TOR network, including the critical nodes insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K), exhibit divergent evolutionary rates between reptiles and mammals; (ii) compared with a proxy for the rest of the genome, genes of the IIS/TOR extracellular network exhibit exceptionally fast evolutionary rates; and (iii) signatures of positive selection and coevolution of the extracellular network suggest reptile- and mammal-specific interactions between members of the network. In reptiles, positively selected sites cluster on the binding surfaces of insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and insulin receptor (INSR); whereas in mammals, positively selected sites clustered on the IGF2 binding surface, suggesting that these hormone-receptor binding affinities are targets of positive selection. Further, contrary to reports that IGF2R binds IGF2 only in marsupial and placental mammals, we found positively selected sites clustered on the hormone binding surface of reptile IGF2R that suggest that IGF2R binds to IGF hormones in diverse taxa and may have evolved in reptiles. These data suggest that key IIS/TOR paralogs have sub- or neofunctionalized between mammals and reptiles and that this network may underlie fundamental life history and physiological differences between these amniote sister clades.


Assuntos
Aves/genética , Evolução Molecular , Variação Genética , Mamíferos/genética , Redes e Vias Metabólicas/genética , Répteis/genética , Transdução de Sinais/fisiologia , Animais , Humanos , Insulina/genética , Insulina/metabolismo , Redes e Vias Metabólicas/fisiologia , Modelos Genéticos , Seleção Genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
17.
Obesity (Silver Spring) ; 23(5): 927-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25864567

RESUMO

OBJECTIVE: Little information exists on how perception of the food (or "energetic") environment affects body composition and reproductive investment. The hypothesis was tested that female mice, who are themselves consuming standard chow diets but who are exposed to conspecifics eating a rich "cafeteria diet," will exhibit altered weight gain and reproductive investment. METHODS: Female C57BL/6 mice were raised on a cafeteria diet. At maturity, subjects were switched to a standard chow diet, and their cage-mates were assigned to consume either a cafeteria diet (treatment, n = 20) or standard chow (control, n = 20). Subjects were mated and pups raised to weaning. Subjects and pups were analyzed for body composition. RESULTS: Treatment had no discernable effect on dam body weight or composition but caused pups to have lower body weight (P = 0.036) and less fat mass (P = 0.041). A nearly significant treatment effect on "time to successful reproduction" (avg. 55 versus 44 days), likely due to increased failed first pregnancies, (14/19 versus 8/19, P = 0.099) was found. CONCLUSIONS: These data indicate that perceived food environment (independent of the diet actually consumed) can produce small pups with less body fat and possibly induce difficulties in pregnancy for dams. Replication and mechanistic studies should follow.


Assuntos
Comportamento Animal/fisiologia , Meio Ambiente , Comportamento Alimentar/fisiologia , Preferências Alimentares/fisiologia , Comportamento Materno/fisiologia , Percepção/fisiologia , Reprodução/fisiologia , Animais , Composição Corporal/fisiologia , Peso Corporal/fisiologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Gravidez , Resultado da Gravidez , Prenhez/fisiologia , Ganho de Peso/fisiologia
18.
F1000Res ; 3: 219, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25324965

RESUMO

BACKGROUND: As part of a coordinated effort to expand our research activity at the interface of Aging and Energetics a team of investigators at The University of Alabama at Birmingham systematically assayed and catalogued the top research priorities identified in leading publications in that domain, believing the result would be useful to the scientific community at large. OBJECTIVE: To identify research priorities and opportunities in the domain of aging and energetics as advocated in the 40 most cited papers related to aging and energetics in the last 4 years. DESIGN: The investigators conducted a search for papers on aging and energetics in Scopus, ranked the resulting papers by number of times they were cited, and selected the ten most-cited papers in each of the four years that include 2010 to 2013, inclusive. RESULTS:   Ten research categories were identified from the 40 papers.  These included: (1) Calorie restriction (CR) longevity response, (2) role of mTOR (mechanistic target of Rapamycin) and related factors in lifespan extension, (3) nutrient effects beyond energy (especially resveratrol, omega-3 fatty acids, and selected amino acids), 4) autophagy and increased longevity and health, (5) aging-associated predictors of chronic disease, (6) use and effects of mesenchymal stem cells (MSCs), (7) telomeres relative to aging and energetics, (8) accretion and effects of body fat, (9) the aging heart,  and (10) mitochondria, reactive oxygen species, and cellular energetics. CONCLUSION: The field is rich with exciting opportunities to build upon our existing knowledge about the relations among aspects of aging and aspects of energetics and to better understand the mechanisms which connect them.

19.
J Gerontol A Biol Sci Med Sci ; 68(5): 521-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23051979

RESUMO

Bivalve molluscs are newly discovered models of successful aging. Here, we test the hypothesis that extremely long-lived bivalves are not uniquely resistant to oxidative stressors (eg, tert-butyl hydroperoxide, as demonstrated in previous studies) but exhibit a multistress resistance phenotype. We contrasted resistance (in terms of organismal mortality) to genotoxic stresses (including topoisomerase inhibitors, agents that cross-link DNA or impair genomic integrity through DNA alkylation or methylation) and to mitochondrial oxidative stressors in three bivalve mollusc species with dramatically differing life spans: Arctica islandica (ocean quahog), Mercenaria mercenaria (northern quahog), and the Atlantic bay scallop, Argopecten irradians irradians (maximum species life spans: >500, >100, and ~2 years, respectively). With all stressors, the short-lived A i irradians were significantly less resistant than the two longer lived species. Arctica islandica were consistently more resistant than M mercenaria to mortality induced by oxidative stressors as well as DNA methylating agent nitrogen mustard and the DNA alkylating agent methyl methanesulfonate. The same trend was not observed for genotoxic agents that act through cross-linking DNA. In contrast, M mercenaria tended to be more resistant to epirubicin and genotoxic stressors, which cause DNA damage by inhibiting topoisomerases. To our knowledge, this is the first study comparing resistance to genotoxic stressors in bivalve mollusc species with disparate longevities. In line with previous studies of comparative stress resistance and longevity, our data extends, at least in part, the evidence for the hypothesis that an association exists between longevity and a general resistance to multiplex stressors, not solely oxidative stress. This work also provides justification for further investigation into the interspecies differences in stress response signatures induced by a diverse array of stressors in short-lived and long-lived bivalves, including pharmacological agents that elicit endoplasmic reticulum stress and cellular stress caused by activation of innate immunity.


Assuntos
Bivalves/genética , Dano ao DNA , Longevidade/genética , Animais , Bivalves/fisiologia , Fenótipo
20.
Mol Ecol ; 22(3): 739-56, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22988821

RESUMO

The complex molecular network that underlies physiological stress response is comprised of nodes (proteins, metabolites, mRNAs, etc.) whose connections span cells, tissues and organs. Variable nodes are points in the network upon which natural selection may act. Thus, identifying variable nodes will reveal how this molecular stress network may evolve among populations in different habitats and how it might impact life-history evolution. Here, we use physiological and genetic assays to test whether laboratory-born juveniles from natural populations of garter snakes (Thamnophis elegans), which have diverged in their life-history phenotypes, vary concomitantly at candidate nodes of the stress response network, (i) under unstressed conditions and (ii) in response to an induced stress. We found that two common measures of stress (plasma corticosterone and liver gene expression of heat shock proteins) increased under stress in both life-history phenotypes. In contrast, the phenotypes diverged at four nodes both under unstressed conditions and in response to stress: circulating levels of reactive oxygen species (superoxide, H(2)O(2)); liver gene expression of GPX1 and erythrocyte DNA damage. Additionally, allele frequencies for SOD2 diverge from neutral markers, suggesting diversifying selection on SOD2 alleles. This study supports the hypothesis that these life-history phenotypes have diverged at the molecular level in how they respond to stress, particularly in nodes regulating oxidative stress. Furthermore, the differences between the life-history phenotypes were more pronounced in females. We discuss the responses to stress in the context of the associated life-history phenotype and the evolutionary pressures thought to be responsible for divergence between the phenotypes.


Assuntos
Colubridae/fisiologia , Ecótipo , Estresse Oxidativo/genética , Animais , Colubridae/genética , Corticosterona/sangue , Dano ao DNA , Feminino , Perfilação da Expressão Gênica , Resposta ao Choque Térmico , Temperatura Alta , Fígado/metabolismo , Masculino , Repetições de Microssatélites , Mitocôndrias Hepáticas/metabolismo , Dados de Sequência Molecular , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo
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