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1.
Health Promot Int ; 38(5)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37706963

RESUMO

Citizen science is rapidly gaining momentum as a means of involving members of the public in research and decision-making in disease prevention and health promotion. However, citizen science projects have predominantly been led by academic researchers and there is limited understanding of how to support the application of citizen science approaches in policy and practice settings. This study aimed to understand the perceptions, motivations and early experiences of applying citizen science approaches in policy and practice settings. Semi-structured interviews were conducted with policy and practice stakeholders who were leading citizen science projects (project partners, n = 7), and their implementation partners (project implementers, n = 11). Participants viewed citizen science as an opportunity to access hard-to-reach data and to enhance engagement with community members to support policy and practice change. Barriers and facilitators of citizen science in policy and practice settings included navigating collaborative relationships, team capacity and resources available to deliver projects, recruitment and engagement of citizen scientists and ethical considerations in the design and implementation of citizen science projects. Findings support the feasibility and wider application of citizen science approaches in health promotion and are being used to inform the development of tools and resources to build capacity in these approaches in policy and practice settings.


Assuntos
Ciência do Cidadão , Humanos , Austrália , Promoção da Saúde , Políticas , Motivação
2.
Proc Natl Acad Sci U S A ; 116(1): 177-186, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30514813

RESUMO

Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism(s) (i.e., phenotypic plasticity and/or genetic evolution) and long-term consequences (e.g., ability to recover phenotypic variation) are unclear. Here we investigate the widespread and dramatic changes in adult migration characteristics of wild Chinook salmon caused by dam construction and other anthropogenic activities. Strikingly, we find an extremely robust association between migration phenotype (i.e., spring-run or fall-run) and a single locus, and that the rapid phenotypic shift observed after a recent dam construction is explained by dramatic allele frequency change at this locus. Furthermore, modeling demonstrates that continued selection against the spring-run phenotype could rapidly lead to complete loss of the spring-run allele, and an empirical analysis of populations that have already lost the spring-run phenotype reveals they are not acting as sustainable reservoirs of the allele. Finally, ancient DNA analysis suggests the spring-run allele was abundant in historical habitat that will soon become accessible through a large-scale restoration (i.e., dam removal) project, but our findings suggest that widespread declines and extirpation of the spring-run phenotype and allele will challenge reestablishment of the spring-run phenotype in this and future restoration projects. These results reveal the mechanisms and consequences of human-induced phenotypic change and highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.


Assuntos
Adaptação Fisiológica , Ecossistema , Salmão , Adaptação Fisiológica/genética , Alelos , Migração Animal , Animais , Loci Gênicos/genética , Variação Genética/genética , Oregon , Salmão/genética
3.
Mol Ecol ; 29(5): 870-885, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012393

RESUMO

Landscape permeability is often explored spatially, but may also vary temporally. Landscape permeability, including partial barriers, influences migratory animals that move across the landscape. Partial barriers are common in rivers where barrier passage varies with streamflow. We explore the influence of partial barriers on the spatial and temporal distribution of migration-linked genotypes of Oncorhynchus mykiss, a salmonid fish with co-occurring resident and migratory forms, in tributaries to the South Fork Eel River, California, USA, Elder and Fox Creeks. We genotyped >4,000 individuals using RAD-capture and classified individuals as resident, heterozygous or migratory genotypes using life history-associated loci. Across four years of study (2014-2017), the permeability of partial barriers varied across dry and wet years. In Elder Creek, the largest waterfall was passable for adults migrating up-river 4-39 days each year. In this stream, the overall spatial pattern, with fewer migratory genotypes above the waterfall, remained true across dry and wet years (67%-76% of migratory alleles were downstream of the waterfall). We also observed a strong relationship between distance upstream and proportion of migratory alleles. In Fox Creek, the primary barrier is at the mouth, and we found that the migratory allele frequency varied with the annual timing of high flow events. In years when rain events occurred during the peak breeding season, migratory allele frequency was high (60%-68%), but otherwise it was low (30% in two years). We highlight that partial barriers and landscape permeability can be temporally dynamic, and this effect can be observed through changing genotype frequencies in migratory animals.


Assuntos
Migração Animal , Variação Genética , Oncorhynchus mykiss/genética , Rios , Movimentos da Água , Animais , California , Frequência do Gene , Genótipo
4.
J Anim Ecol ; 89(8): 1799-1810, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32358976

RESUMO

Fire-induced changes in the abundance and distribution of organisms, especially plants, can alter resource landscapes for mobile consumers driving bottom-up effects on their population sizes, morphologies and reproductive potential. We expect these impacts to be most striking for obligate visitors of plants, like bees and other pollinators, but these impacts can be difficult to interpret due to the limited information provided by forager counts in the absence of survival or fitness proxies. Increased bumble bee worker abundance is often coincident with the pulses of flowers that follow recent fire. However, it is unknown if observed postfire activity is due to underlying population growth or a stable pool of colonies recruiting more foragers to abundant resource patches. This distinction is necessary for determining the net impact of disturbance on bumble bees: are there population-wide responses or do just a few colonies reap the rewards? We estimated colony abundance before and after fire in burned and unburned areas using a genetic mark-recapture framework. We paired colony abundance estimates with measures of body size, counts of queens, and estimates of foraging and dispersal to assess changes in worker size, reproductive output, and landscape-scale movements. Higher floral abundance following fire not only increased forager abundance but also the number of colonies from which those foragers came. Importantly, despite a larger population size, we also observed increased mean worker size. Two years following fire, queen abundance was higher in both burned and unburned sites, potentially due to the dispersal of queens from burned into unburned areas. The effects of fire were transient; within two growing seasons, worker abundance was substantially reduced across the entire sampling area and body sizes were similar between burned and unburned sites. Our results reveal how disturbance can temporarily release populations from resource limitation, boosting the genetic diversity, body size, and reproductive output of populations. Given that the effects of fire on bumble bees acted indirectly through pulsed resource availability, it is likely our results are generalizable to other situations, such as habitat restorations, where resource density is enhanced within the landscape.


Assuntos
Incêndios Florestais , Animais , Abelhas , Ecossistema , Flores , Densidade Demográfica , Reprodução
5.
J Hered ; 111(6): 548-563, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33125465

RESUMO

The preservation of life history and other phenotypic complexity is central to the resilience of Pacific salmon stocks. Steelhead (Oncorhynchus mykiss) express a diversity of life-history strategies such as the propensity to migrate (anadromy/residency) and the timing and state of maturation upon return to freshwater (run-timing), providing an opportunity to study adaptive phenotypic complexity. Historically, the Eel River supported upwards of 1 million salmon and steelhead, but the past century has seen dramatic declines of all salmonids in the watershed. Here we investigate life-history variation in Eel River steelhead by using Rapture sequencing, on thousands of individuals, to genotype the region diagnostic for run-timing (GREB1L) and the region strongly associated with residency/anadromy (OMY5) in the Eel River and other locations, as well as determine patterns of overall genetic differentiation. Our results provide insight into many conservation-related issues. For example, we found that distinct segregation between winter and summer-run steelhead correlated with flow-dependent barriers in major forks of the Eel, that summer-run steelhead inhabited the upper Eel prior to construction of an impassable dam, and that both life history and overall genetic diversity have been maintained in the resident trout population above; and we found no evidence of the summer-run allele in the South Fork Eel, indicating that summer run-timing cannot be expected to arise from standing genetic variation in this and other populations that lack the summer-run phenotype. The results presented in this study provide valuable information for designing future restoration and management strategies for O. mykiss in Northern California and beyond.


Assuntos
Conservação dos Recursos Naturais , Variação Genética , Características de História de Vida , Oncorhynchus mykiss/fisiologia , Migração Animal , Animais , California , Ecologia , Espécies em Perigo de Extinção , Genótipo , Oncorhynchus mykiss/genética , Fenótipo , Rios , Estações do Ano
6.
Mol Ecol ; 28(20): 4636-4647, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31495012

RESUMO

Contact zones between species provide a unique opportunity to test whether taxa can hybridize or not. Cross-breeding or hybridization between closely related taxa can promote gene flow (introgression) between species, adaptation, or even speciation. Though hybridization events may be short-lived and difficult to detect in the field, genetic data can provide information about the level of introgression between closely related taxa. Hybridization can promote introgression between species, which may be an important evolutionary mechanism for either homogenization (reversing initial divergence between species) or reproductive isolation (potentially leading to speciation). Here, we used thousands of genetic markers from nuclear DNA to detect hybridization between two parapatric frog species (Rana boylii and Rana sierrae) in the Sierra Nevada of California. Based on principal components analysis, admixture, and analysis of heterozygosity at species diagnostic SNPs, we detected two F1 hybrid individuals in the Feather River basin, as well as a weak signal of introgression and gene flow between the frog species compared with frog populations from two other adjacent watersheds. This study provides the first documentation of hybridization and introgression between these two species, which are of conservation concern.


Assuntos
Quimera/genética , Especiação Genética , Hibridização Genética/genética , Ranidae/classificação , Animais , California , Fluxo Gênico/genética , Polimorfismo de Nucleotídeo Único/genética , Análise de Componente Principal , Ranidae/genética
7.
Mol Phylogenet Evol ; 140: 106597, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31445201

RESUMO

When incipient species meet in secondary contact, natural selection can rapidly reduce costly reproductive interactions by directly targeting reproductive traits. This process, called reproductive character displacement (RCD), leaves a characteristic pattern of geographic variation where divergence of traits between species is greater in sympatry than allopatry. However, because other forces can also cause similar patterns, care must be given in separating pattern from process. Here we show how the phylo-comparative method together with genomic data can be used to evaluate evolutionary processes at the population level in closely related species. Using this framework, we test the role of RCD in speciation of two cricket species endemic to Anatolian mountains by quantifying patterns of character displacement, rates of evolution and adaptive divergence. Our results show differing patterns of character displacement between species for reproductive vs. non-reproductive characters and strong patterns of asymmetric divergence. We demonstrate diversification results from rapid divergence of reproductive traits towards multiple optima under the dual influence of strong drift and selection. These results present the first solid evidence for RCD in Anatolian mountains, quantify the amount of drift and selection necessary for RCD to lead to speciation, and demonstrate the utility of phylo-comparative methods for quantifying evolutionary parameters at the population level.


Assuntos
Deriva Genética , Gryllidae/classificação , Gryllidae/genética , Filogenia , Seleção Genética , Animais , Loci Gênicos , Geografia , Gryllidae/anatomia & histologia , Funções Verossimilhança , Masculino , Fenótipo , Reprodução/genética , Turquia
8.
Mol Ecol ; 27(4): 839-842, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29442386

RESUMO

The age of DHP and how pupfish colonized Devils Hole have always been a topic of interest. Recently, two different publications (Martin, Crawford, Turner, & Simons, & Saglam et al., ) tackled this issue using genomic data sets and demographic models but came to widely different conclusions. In their comment, Martin and Höhne () argue that our results (Saglam et al., ) were misleading because we used inappropriate calibration information and biased a priori assumptions. They then re-analysed our data using a "biologically informed" mutation rate prior and concluded that our data support a much younger age of DHP (12.6 kya) as opposed to 60 kya reported in our study. Below we will summarize why their arguments do not hold up and explore some of the inconsistencies between their claims and what was actually presented in our study. Furthermore, we will demonstrate their re-analyses provide no new information compared to what was presented in our original manuscript and reinforce our estimate of a 60 kya divergence of DHP as outweighing competing hypotheses.


Assuntos
Genômica , Taxa de Mutação , Animais , Calibragem , Demografia , Andorinhas
9.
Mol Ecol ; 27(21): 4189-4199, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30171778

RESUMO

Identifying the genetic architecture of complex phenotypes is a central goal of modern biology, particularly for disease-related traits. Genome-wide association methods are a classical approach for identifying the genomic basis of variation in disease phenotypes, but such analyses are particularly challenging in natural populations due to sample size difficulties. Extensive mark-recapture data, strong linkage disequilibrium and a lethal transmissible cancer make the Tasmanian devil (Sarcophilus harrisii) an ideal model for such an association study. We used a RAD-capture approach to genotype 624 devils at ~16,000 loci and then used association analyses to assess the heritability of three cancer-related phenotypes: infection case-control (where cases were infected devils and controls were devils that were never infected), age of first infection and survival following infection. The SNP array explained much of the phenotypic variance for female survival (>80%) and female case-control (>61%). We found that a few large-effect SNPs explained much of the variance for female survival (~5 SNPs explained >61% of the total variance), whereas more SNPs (~56) of smaller effect explained less of the variance for female case-control (~23% of the total variance). By contrast, these same SNPs did not account for a significant proportion of phenotypic variance in males, suggesting that the genetic bases of these traits and/or selection differ across sexes. Loci involved with cell adhesion and cell-cycle regulation underlay trait variation, suggesting that the devil immune system is rapidly evolving to recognize and potentially suppress cancer growth through these pathways. Overall, our study provided necessary data for genomics-based conservation and management in Tasmanian devils.


Assuntos
Resistência à Doença/genética , Marsupiais/genética , Neoplasias/veterinária , Animais , Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Feminino , Estudos de Associação Genética/veterinária , Genômica , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Taxa de Sobrevida , Tasmânia
10.
J Adolesc ; 65: 133-140, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29597102

RESUMO

We explored Canadian adolescents', emergent adults', and adults' understandings of deception in computer mediated communication (CMC) compared to face to face (FtF). Participants between 13 and 50 years read vignettes of different types of questionable behaviour that occurred online or in real life, and were asked to judge whether deception was involved, and the acceptability of the behaviour. Age groups evaluated deception similarly; however, adolescents held slightly different views from adults about what constitutes deception, suggesting that the understanding of deception continues to develop into adulthood. Furthermore, CMC behaviour was rated as more deceptive than FtF in general, and participants scoring higher on compassion perceived vignettes to be more deceptive. This study is a step towards better understanding the relationships between perceptions of deception across adolescence into adulthood, mode of communication, and compassion, and may have implications for how adults communicate with youth about deception in CMC and FtF contexts.


Assuntos
Desenvolvimento do Adolescente , Enganação , Relações Interpessoais , Mídias Sociais , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Percepção , Adulto Jovem
11.
Health Promot J Austr ; 29(3): 321-327, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30511486

RESUMO

ISSUE ADDRESSED: Hello Sunday Morning (HSM) is an online program that encourages people to commit to a period of non-drinking and blog about their experiences. Among a sample of Victorian HSM users, we aimed to explore the barriers faced and the strategies adopted to maximise potential for achieving temporary abstinence. METHODS: A content analysis of blog data from 154 HSM users (a total of 2844 blog posts) was undertaken by three researchers. Participants were predominantly women aged 30-50 years. RESULTS: The most common barriers to achieving temporary alcohol abstinence reported by participants were stress and tiredness, pervasiveness of drinking in social life, negative effects from not drinking and negative reactions from others. The strategies most commonly implemented included drawing on HSM and other non-drinking networks, self-talk, engaging in non-alcohol-related activities and substituting alcohol with other drinks. CONCLUSIONS: Although significant individual and systemic barriers to abstaining from alcohol were identified by HSM users, multiple strategies were identified and effectively utilised to overcome these barriers. SO WHAT?: We suggest that the virtual support from an online community with a shared interest in reducing their alcohol use appears to be a useful health promotion strategy for temporarily reducing consumption, particularly for women.


Assuntos
Abstinência de Álcool/psicologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Consumo de Bebidas Alcoólicas/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde/métodos , Adulto , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Mídias Sociais , Rede Social , Vitória
12.
J Ind Microbiol Biotechnol ; 44(4-5): 563-572, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27858169

RESUMO

Streptomyces cinnamoneus DSM 40646 produces the Class II lantibiotic cinnamycin which possesses an unusual mechanism of action, binding to the membrane lipid phosphatidylethanolamine (PE) to elicit its antimicrobial activity. A comprehensive analysis of the cinnamycin biosynthetic gene cluster has unveiled a novel mechanism of immunity in which the producing organism methylates its entire complement of PE prior to the onset of cinnamycin production. Deletion of the PE methyl transferase gene cinorf10, or the two-component regulatory system (cinKR) that controls its expression, leads not only to sensitivity to the closely related lantibiotic duramycin, but also abolishes cinnamycin production, presumably reflecting a fail-safe mechanism that serves to ensure that biosynthesis does not occur until immunity has been established.


Assuntos
Proteínas de Bactérias/genética , Bacteriocinas/biossíntese , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Peptídeos Cíclicos/biossíntese , Streptomyces/genética , Proteínas de Bactérias/metabolismo , Bacteriocinas/metabolismo , Sequência de Bases , Deleção de Genes , Família Multigênica , Peptídeos/metabolismo , Fosfatidiletanolaminas/metabolismo , Streptomyces/metabolismo
13.
Mol Ecol ; 25(16): 3962-73, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27314880

RESUMO

The Devils Hole pupfish (Cyprinodon diabolis; DHP) is an icon of conservation biology. Isolated in a 50 m(2) pool (Devils Hole), DHP is one of the rarest vertebrate species known and an evolutionary anomaly, having survived in complete isolation for thousands of years. However, recent findings suggest DHP might be younger than commonly thought, potentially introduced to Devils Hole by humans in the past thousand years. As a result, the significance of DHP from an evolutionary and conservation perspective has been questioned. Here we present a high-resolution genomic analysis of DHP and two closely related species, with the goal of thoroughly examining the temporal divergence of DHP. To this end, we inferred the evolutionary history of DHP from multiple random genomic subsets and evaluated four historical scenarios using the multispecies coalescent. Our results provide substantial information regarding the evolutionary history of DHP. Genomic patterns of secondary contact present strong evidence that DHP were isolated in Devils Hole prior to 20-10 ka and the model best supported by geological history and known mutation rates predicts DHP diverged around 60 ka, approximately the same time Devils Hole opened to the surface. We make the novel prediction that DHP colonized and have survived in Devils Hole since the cavern opened, and the two events (colonization and collapse of the cavern's roof) were caused by a common geologic event. Our results emphasize the power of evolutionary theory as a predictive framework and reaffirm DHP as an important evolutionary novelty, worthy of continued conservation and exploration.


Assuntos
Evolução Biológica , Peixes Listrados/genética , Filogenia , Animais , Conservação dos Recursos Naturais , Clima Desértico , Espécies em Perigo de Extinção , Fluxo Gênico , Genômica , Modelos Genéticos , Taxa de Mutação , Polimorfismo de Nucleotídeo Único , Estados Unidos
14.
Epilepsia ; 57(7): e135-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27215589

RESUMO

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts.


Assuntos
Morte Súbita , Epilepsia/complicações , Epilepsia/mortalidade , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Evol Appl ; 17(6): e13705, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38832083

RESUMO

Intraspecific diversity plays a critical role in the resilience of Chinook salmon populations. California's Central Valley (CV) historically hosted one of the most diverse population complexes of Chinook salmon in the world. However, anthropogenic factors have dramatically decreased this diversity, with severe consequences for population resilience. Here we use next generation sequencing and an archive of thousands of tissue samples collected across two decades during the juvenile outmigration to evaluate phenotypic diversity between and within populations of CV Chinook salmon. To account for highly heterogeneous sample qualities in the archive dataset, we develop and test an approach for population and subpopulation assignments of CV Chinook salmon that allows inclusion of relatively low-quality samples while controlling error rates. We find significantly distinct outmigration timing and body size distributions for each population and subpopulation. Within the archive dataset, spring run individuals that assigned to the Mill and Deer Creeks subpopulation exhibited an earlier and broader outmigration distribution as well as larger body sizes than individuals that assigned to the Butte Creek subpopulation. Within the fall run population, individuals that assigned to the late-fall run subpopulation also exhibited an earlier and broader outmigration distribution and larger body sizes than other fall run fish in our dataset. These results highlight the importance of distinct subpopulations for maintaining remaining diversity in CV Chinook salmon, and demonstrates the power of genomics-based population assignments to aid the study and management of intraspecific diversity.

16.
J Appl Biomech ; 29(2): 205-13, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22813644

RESUMO

The objective of the study was to determine if prophylactic ankle bracing worn by females during landings produces abnormal lower extremity mechanics. Angular kinematic and ground reaction force (GRF) data were obtained for 16 athletically experienced females who performed brace and no-brace drop landings. The brace condition displayed reduced in/external rotation and flexion displacements about the ankle and knee joints and increased vertical and mediolateral GRF peak magnitudes and rate of vertical GRF application (paired t test, P < .05). The ankle and knee joints landed in a less plantar flexed and more flexed position, respectively. No significant ab/adduction outcomes may have occurred due to interparticipant variability and/or a lack of brace restriction. Conclusion: During typical landings, this lace-up brace increases vertical GRF, decreases ankle and knee joint displacements of flexion and int/external rotation, but minimally affects ab/adduction displacements.


Assuntos
Traumatismos do Tornozelo/prevenção & controle , Braquetes , Traumatismos do Joelho/prevenção & controle , Traumatismos do Tornozelo/fisiopatologia , Antropometria , Fenômenos Biomecânicos , Feminino , Humanos , Traumatismos do Joelho/fisiopatologia , Rotação , Esportes/fisiologia , Inquéritos e Questionários , Adulto Jovem
17.
Nat Commun ; 13(1): 660, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115518

RESUMO

Many traits are subject to assortative mating, with recent molecular genetic findings confirming longstanding theoretical predictions that assortative mating induces long range dependence across causal variants. However, all marker-based heritability estimators implicitly assume mating is random. We provide mathematical and simulation-based evidence demonstrating that both method-of-moments and likelihood-based estimators are biased in the presence of assortative mating and derive corrected heritability estimators for traits subject to assortment. Finally, we demonstrate that the empirical patterns of estimates across methods and sample sizes for real traits subject to assortative mating are congruent with expected assortative mating-induced biases. For example, marker-based heritability estimates for height are 14% - 23% higher than corrected estimates using UK Biobank data.


Assuntos
Algoritmos , Genética Populacional/métodos , Modelos Genéticos , Reprodução/genética , Viés , Simulação por Computador , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Funções Verossimilhança , Desequilíbrio de Ligação , Masculino , Análise da Randomização Mendeliana/métodos , Fenótipo , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável
18.
Nature ; 435(7046): 1257-61, 2005 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-15988528

RESUMO

SCF-type E3 ubiquitin ligases are multi-protein complexes required for polyubiquitination and subsequent degradation of target proteins by the 26S proteasome. Cullins, together with the RING-finger protein Rbx1, form the catalytic core of the ligase, and recruit the substrate-recognition module. Cycles of covalent modification of cullins by the ubiquitin-like molecule Nedd8 (neddylation) and removal of Nedd8 by the COP9 signalosome (deneddylation) positively regulate E3 ligase activity. Here we report the identification and analysis of a widely conserved protein that is required for cullin neddylation in the nematode Caenorhabditis elegans and the yeast Saccharomyces cerevisiae. C. elegans DCN-1 and S. cerevisiae Dcn1p (defective in cullin neddylation) are characterized by a novel UBA-like ubiquitin-binding domain and a DUF298 domain of unknown function. Consistent with their requirements for neddylation, DCN-1 and Dcn1p directly bind Nedd8 and physically associate with cullins in both species. Moreover, overexpression of Dcn1p in yeast results in the accumulation of Nedd8-modified cullin Cdc53p. Both in vivo and in vitro experiments indicate that Dcn1p does not inhibit deneddylation of Cdc53p by the COP9 signalosome, but greatly increases the kinetics of the neddylation reaction.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Sequência Conservada , Proteínas Culina/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Ubiquitinas/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Complexo do Signalossomo COP9 , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Catálise , Proteínas Culina/genética , Complexos Multiproteicos/metabolismo , Peptídeo Hidrolases/metabolismo , Ligação Proteica , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases
19.
Proc Natl Acad Sci U S A ; 105(45): 17510-5, 2008 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-18988741

RESUMO

All of the genetic elements necessary for the production of the antibiotic methylenomycin (Mm) and its regulation are contained within the 22-kb mmy-mmf gene cluster, which is located on the 356-kb linear plasmid SCP1 of Streptomyces coelicolor A3(2). A putative operon of 3 genes within this gene cluster, mmfLHP, was proposed to direct the biosynthesis of an A-factor-like signaling molecule, which could play a role in the regulation of Mm biosynthesis. The mmfLHP operon was expressed under the control of its native promoter in S. coelicolor M512, a host lacking the SCP1 plasmid, and the ability to produce prodiginine and actinorhodin antibiotics. Comparative metabolic profiling led to the identification and structure elucidation of a family of 5 new 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids (AHFCAs), collectively termed Mm furans (MMFs), as the products of the mmfLHP genes. MMFs specifically induce the production of the Mm antibiotics in S. coelicolor. Comparative genomics analyses and searches of the natural product chemistry literature indicated that other streptomycetes may produce AHFCAs, suggesting that they could form a general class of antibiotic biosynthesis inducers in Streptomyces species, with analogous functions to the better known gamma-butyrolactone regulatory molecules.


Assuntos
Antibacterianos/biossíntese , Furanos/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Família Multigênica/genética , Streptomyces coelicolor/genética , Cromatografia Líquida de Alta Pressão , Biologia Computacional , Primers do DNA/genética , Furanos/química , Genômica/métodos , Espectrometria de Massas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/genética , Plasmídeos/genética
20.
Mol Microbiol ; 71(3): 763-78, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19054329

RESUMO

Bioinformatic analysis of the plasmid-linked gene cluster associated with biosynthesis of methylenomycin (Mm) suggested that part of the cluster directs synthesis of a gamma-butyrolactone-like autoregulator. Autoregulator activity could be extracted from culture fluids, but differed from gamma-butyrolactones in being alkali resistant. The activity has recently been shown to comprise a series of novel autoregulator molecules, the methylenomycin furans (termed MMF). MMF autoregulator activity is shown to account for the ability of certain Mm non-producing mutants to act as 'secretors' in cosynthesis with other 'convertor' mutants. Three genes implicated in MMF biosynthesis are flanked by two regulatory genes, which are related to genes for gamma-butyrolactone-binding proteins. Genetic evidence suggests that these two genes encode components of a hetero-oligomeric repressor of MMF and Mm biosynthesis. The Mm biosynthetic genes themselves depend on the activator gene mmyB, which appears to be repressed by the putative MmyR/MmfR complex until enough MMF accumulates to release repression. The presence of TTA codons in mmyB and the main MMF biosynthetic gene causes Mm production to be dependent on the pleiotropically acting bldA gene, which encodes the tRNA for the rarely used UUA codon.


Assuntos
Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Streptomyces coelicolor/genética , Proteínas de Bactérias/genética , Códon , DNA Bacteriano/genética , Furanos/metabolismo , Genes Bacterianos , Metabolômica , Família Multigênica , Peptídeos/metabolismo , Biossíntese de Proteínas , Streptomyces coelicolor/metabolismo
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