Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.747
Filtrar
2.
Insect Sci ; 27(2): 266-275, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30102013

RESUMO

The interaction of house dust mites (HDM) and microorganisms is the key factor in the survival of these mites in human-made environments. Spent growth medium (SPGM) provides the rest of the diet, along with dead mite bodies and microorganisms. SPGM represents a source of microorganisms for the recolonization of mite food and the mite digestive tract. An experiment was performed to observe how adding SPGM to the HDM diet affects HDM population growth, the microbiome composition and the microbial respiration in microcosms. We analyzed American house dust mite (Dermatophagoides farinae) and European house dust mite (Dermatophagoides pteronyssinus) originating from control diets and diets treated with an extract of SPGM from 1- and 3-month-old mite cultures. The microbiome was described using 16S and 18S barcode sequencing. The composition of the bacterial and fungal microbiomes differed between the HDM species, but the SPGM treatment influenced only the bacterial profile of D. farinae. In the D. farinae microbiome of specimens on SPGM-treated diets compared to those of the control situation, the Lactobacillus profile decreased, while the Cardinium, Staphylococcus, Acinetobacter, and Sphingomonas profiles increased. The addition of SPGM extract decreased the microbial respiration in the microcosms with and without mites in almost all cases. Adding SPGM did not influence the population growth of D. farinae, but it had a variable effect on D. pteronyssinus. The results indicated that the HDM are marginally influenced by the microorganisms in their feces.


Assuntos
Dermatophagoides pteronyssinus/microbiologia , Microbiota , Animais , Meios de Cultura , Feminino , Aptidão Genética , Masculino , Crescimento Demográfico
3.
Insect Sci ; 27(1): 58-68, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29676854

RESUMO

"Candidatus Liberibacter solanacearum" (Lso) are phloem-restricted and unculturable Gram-negative bacteria. Presently five haplotypes have been identified worldwide; but only haplotypes A and B are associated with the vector Bactericera cockerelli (Sulc.) in the Americas. Previous studies showed that Lso-infection reduces B. cockerelli reproductive output and that Lso haplotype B is more pathogenic than Lso haplotype A. To understand the interaction of Lso haplotype B and B. cockerelli, the fitness of Lso-free and Lso B-infected insects, and the expression of vitellogenin (BcVg1-like), a gene involved directly in the insect reproduction were analyzed. Statistical differences in the number of eggs oviposited, and the total number of progeny nymphs and adults were found among crosses of insects with or without Lso. Significant differences in sex proportions were found between Lso B-infected and Lso-free crosses: a higher proportion of F1 adult females were obtained from Lso B-infected mothers. A significant reduction of BcVg1-like was observed in crosses performed with Lso B-infected females compared to the Lso-free insects. In female cohorts of different age, a significant reduction of BcVg1-like expression was measured in 7-d-old Lso B-infected females (virgin and mated) compared with 7-d-old Lso-free females (virgin and mated), respectively. The reduction of BcVg1-like transcript was associated with a lower number of developing oocytes observed in female's reproductive systems. Overall, this study represents the first step to understand the interaction of Lso B with B. cockerelli, highlighting the effect of Lso B infection on egg production, BcVg1-like expression, and oocyte development.


Assuntos
Aptidão Genética , Hemípteros/fisiologia , Rhizobiaceae/fisiologia , Vitelogênese , Animais , Hemípteros/genética , Hemípteros/crescimento & desenvolvimento , Hemípteros/microbiologia , Lycopersicon esculentum/microbiologia , Lycopersicon esculentum/fisiologia , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , Ninfa/fisiologia , Doenças das Plantas/microbiologia
4.
Genome Biol Evol ; 11(11): 3283-3290, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31688900

RESUMO

Population bottlenecks leading to a drastic reduction of the population size are common in the evolutionary dynamics of natural populations; their occurrence is known to have implications for genome evolution due to genetic drift, the consequent reduction in genetic diversity, and the rate of adaptation. Nevertheless, an empirical characterization of the effect of population bottleneck size on evolutionary dynamics of bacteria is currently lacking. In this study, we show that selective conditions have a stronger effect on the evolutionary history of bacteria in comparison to population bottlenecks. We evolved Escherichia coli populations under three different population bottleneck sizes (small, medium, and large) in two temperature regimes (37 °C and 20 °C). We find a high genetic diversity in the large in comparison to the small bottleneck size. Nonetheless, the cold temperature led to reduced genetic diversity regardless the bottleneck size; hence, the temperature has a stronger effect on the genetic diversity in comparison to the bottleneck size. A comparison of the fitness gain among the evolved populations reveals a similar pattern where the temperature has a significant effect on the fitness. Our study demonstrates that population bottlenecks are an important determinant of bacterial evolvability; their consequences depend on the selective conditions and are best understood via their effect on the standing genetic variation.


Assuntos
Escherichia coli/crescimento & desenvolvimento , Escherichia coli/genética , Deriva Genética , Adaptação Biológica , Evolução Biológica , Escherichia coli/fisiologia , Aptidão Genética , Variação Genética , Polimorfismo de Nucleotídeo Único , Seleção Genética , Temperatura Ambiente
5.
J Fish Dis ; 42(12): 1687-1696, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617230

RESUMO

Bacterial antibiotic resistance is one of the main healthcare problems currently. Apart from reducing antibiotic efficacy, it has awakened the interest of scientists due to its association with bacterial fitness and virulence. Interestingly, antibiotic resistance can be a source of both increased fitness and decreased fitness, even though the molecular basis of these relationships remains unknown. The aim of this work is to define the effects of sub-MIC concentrations of cefotaxime, an antibiotic extensively used in clinical practice, on the physiology and virulence of Yersinia ruckeri and to determine the importance of these sub-MIC concentrations for the selection of antibiotic-resistant mutants in the aquatic environment. Results indicated that exposure to sub-MIC concentrations of cefotaxime selected Y. ruckeri populations with irreversible alterations in the physiology, such as slow growth, aggregation in liquid cultures and modification of the colony morphology. These bacteria also displayed changes in the OMPs and LPS profiles and a full attenuation of virulence. An overexpression of the envelope stress regulator RpoE was also detected after exposure to the antibiotic. In conclusion, exposure to cefotaxime selected, at high frequency, Y. ruckeri strains that survive the antibiotic stress at the expense of a fitness cost and the loss of virulence.


Assuntos
Antibacterianos/farmacologia , Cefotaxima/farmacologia , Farmacorresistência Bacteriana/genética , Virulência , Yersinia ruckeri/efeitos dos fármacos , Yersinia ruckeri/genética , Animais , Proteínas de Bactérias/genética , Doenças dos Peixes/microbiologia , Teste de Complementação Genética , Aptidão Genética , Testes de Sensibilidade Microbiana , Oncorhynchus mykiss/microbiologia , Porinas/genética , Seleção Genética , Yersiniose/microbiologia , Yersiniose/veterinária , Yersinia ruckeri/patogenicidade
6.
Dis Aquat Organ ; 136(1): 37-49, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31575833

RESUMO

Fluctuating asymmetry (FA), defined as random deviations from perfect bilateral symmetry, is assumed to reflect developmental instability. FA is predicted to increase in response to environmental stress, including parasite infection. In addition, based on theory we predict a higher FA in sexually selected traits, due to their greater sensitivity to stress. We investigated the relationships between FA, parasitism and reproductive fitness in 2 species of gammarid crustacean, incorporating both sexual and non-sexual traits. We tested the hypothesis that gammarids infected by vertically transmitted Microsporidia will display higher levels of FA than those infected by horizontally transmitted trematodes, because vertically transmitted Microsporidia can be present at the earliest stages of host development. We found little evidence for a relationship between FA and fecundity in Gammarus spp.; however, egg diameter for infected female Gammarus duebeni was significantly smaller than uninfected female G. duebeni. FA was not correlated with brood size in females or with sperm number in males. In contrast to our prediction, we report a lower relative FA in response to sexual traits than non-sexual traits. However, FA in sexual traits was found to be higher in males than females, supporting the theory that sexual selection leads to increased FA. Additionally, we report a negative correlation between FA and both trematode (Podocotyle atomon) and PCR-positive microsporidian (Nosema granulosis and Dictyocoela duebenum) infections and interpret these results in the context of the parasites' transmission strategies. FA in G. duebeni and G. zaddachi appears to associate with trematode and microsporidian presence, although reproductive fitness is less altered by infection.


Assuntos
Anfípodes/fisiologia , Anfípodes/parasitologia , Aptidão Genética , Animais , Feminino , Interações Hospedeiro-Parasita , Masculino , Doenças Parasitárias em Animais/fisiopatologia , Doenças Parasitárias em Animais/transmissão , Reprodução
7.
Nat Ecol Evol ; 3(11): 1539-1551, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31611676

RESUMO

Trade-offs constrain the improvement of performance of multiple traits simultaneously. Such trade-offs define Pareto fronts, which represent a set of optimal individuals that cannot be improved in any one trait without reducing performance in another. Surprisingly, experimental evolution often yields genotypes with improved performance in all measured traits, perhaps indicating an absence of trade-offs at least in the short term. Here we densely sample adaptive mutations in Saccharomyces cerevisiae to ask whether first-step adaptive mutations result in trade-offs during the growth cycle. We isolated thousands of adaptive clones evolved under carefully chosen conditions and quantified their performances in each part of the growth cycle. We too find that some first-step adaptive mutations can improve all traits to a modest extent. However, our dense sampling allowed us to identify trade-offs and establish the existence of Pareto fronts between fermentation and respiration, and between respiration and stationary phases. Moreover, we establish that no single mutation in the ancestral genome can circumvent the detected trade-offs. Finally, we sequenced hundreds of these adaptive clones, revealing new targets of adaptation and defining the genetic basis of the identified trade-offs.


Assuntos
Adaptação Fisiológica , Aptidão Genética , Aclimatação , Mapeamento de Nucleotídeos , Fenótipo
8.
Nat Commun ; 10(1): 4301, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541093

RESUMO

Generalist bacterial predators are likely to strongly shape many important ecological and evolutionary features of microbial communities, for example by altering the character and pace of molecular evolution, but investigations of such effects are scarce. Here we report how predator-prey interactions alter the evolution of fitness, genomes and phenotypic diversity in coevolving bacterial communities composed of Myxococcus xanthus as predator and Escherichia coli as prey, relative to single-species controls. We show evidence of reciprocal adaptation and demonstrate accelerated genomic evolution specific to coevolving communities, including the rapid appearance of mutator genotypes. Strong parallel evolution unique to the predator-prey communities occurs in both parties, with predators driving adaptation at two prey traits associated with virulence in bacterial pathogens-mucoidy and the outer-membrane protease OmpT. Our results suggest that generalist predatory bacteria are important determinants of how complex microbial communities and their interaction networks evolve in natural habitats.


Assuntos
Bactérias/genética , Evolução Molecular , Interações Microbianas/genética , Interações Microbianas/fisiologia , Microbiota/genética , Microbiota/fisiologia , Adaptação Fisiológica , Fenômenos Fisiológicos Bacterianos/genética , Proteínas de Bactérias/genética , Coevolução Biológica , Escherichia coli/genética , Escherichia coli/fisiologia , Aptidão Genética , Myxococcus xanthus/genética , Myxococcus xanthus/fisiologia , Fenótipo , Porinas/genética , Virulência
9.
PLoS Pathog ; 15(9): e1007948, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31560731

RESUMO

We have used a transposon insertion sequencing (TIS) approach to establish the fitness landscape of the African Salmonella enterica serovar Typhimurium ST313 strain D23580, to complement our previous comparative genomic and functional transcriptomic studies. We used a genome-wide transposon library with insertions every 10 nucleotides to identify genes required for survival and growth in vitro and during infection of murine macrophages. The analysis revealed genomic regions important for fitness under two in vitro growth conditions. Overall, 724 coding genes were required for optimal growth in LB medium, and 851 coding genes were required for growth in SPI-2-inducing minimal medium. These findings were consistent with the essentiality analyses of other S. Typhimurium ST19 and S. Typhi strains. The global mutagenesis approach also identified 60 sRNAs and 413 intergenic regions required for growth in at least one in vitro growth condition. By infecting murine macrophages with the transposon library, we identified 68 genes that were required for intra-macrophage replication but did not impact fitness in vitro. None of these genes were unique to S. Typhimurium D23580, consistent with a high conservation of gene function between S. Typhimurium ST313 and ST19 and suggesting that novel virulence factors are not involved in the interaction of strain D23580 with murine macrophages. We discovered that transposon insertions rarely occurred in many pBT1 plasmid-encoded genes (36), compared with genes carried by the pSLT-BT virulence plasmid and other bacterial plasmids. The key essential protein encoded by pBT1 is a cysteinyl-tRNA synthetase, and our enzymological analysis revealed that the plasmid-encoded CysRSpBT1 had a lower ability to charge tRNA than the chromosomally-encoded CysRSchr enzyme. The presence of aminoacyl-tRNA synthetases in plasmids from a range of Gram-negative and Gram-positive bacteria suggests that plasmid-encoded essential genes are more common than had been appreciated.


Assuntos
Salmonella typhimurium/fisiologia , Salmonella typhimurium/patogenicidade , Animais , Elementos de DNA Transponíveis , DNA Bacteriano/genética , Genes Bacterianos , Aptidão Genética , Macrófagos/microbiologia , Camundongos , Plasmídeos/genética , Células RAW 264.7 , Salmonelose Animal/microbiologia , Salmonella typhimurium/genética , Virulência/genética , Virulência/fisiologia
10.
Int J Mycobacteriol ; 8(3): 287-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512606

RESUMO

Background: While, bacteria resistance mutations can affect competitive fitness, given our multidrug-resistant (MDR) prevalence, we conducted this study to determine the impact of MDR on the competitive fitness of Mycobacterium tuberculosis (MTB) complex MDR strains. We conducted a cross-sectional study at the University Clinical Research Center (UCRC) from January to December 2017. New TB patients over aged of 18 were recruited at University teaching hospital and health reference centers of Bamako in USTTB Ethical committee approved protocols. Methods: MDR and drug-susceptible (wild-type [WT]) MTB strains (T1 and Beijing) and MTB H37Rv were competed on solid media in UCRC's Tuberculosis Laboratory. Competitive and individual cultures were incubated for 14 days at 37°C with 7% CO2. Number of generation, generation time, and relative competitive fitness (W) of the strains were calculated. Data were analyzed with Epi-Info 7.1.5.2 software (CDC). P value was considered significant when it was <0.05. Scientific calculator (CS-82TL) was used for competitive fitness parameters calculations. Results: We performed 24 competitive cultures and 10 individual cultures. In individual cultures, strains' generation number was for Beijing (WT: 4.60 and mutant MR: 4.40), T1 (WT: 2.69 and MR: 2.37), and H37Rv: 2.91. Generation number of WT strains was less than those of MDR strains in both individual and competitive culture. Relative competitive fitness was below 1 (W<1) in 83.3%. Conclusion: MDR strains were less competitive than WT strains in 83.3% of cases. Resistant mutation impacts bacteria fitness.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Aptidão Genética , Mutação , Mycobacterium tuberculosis/genética , Genótipo , Humanos , Mali , Mycobacterium tuberculosis/efeitos dos fármacos , Estudos Prospectivos , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
11.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502584

RESUMO

The role of genetic relatedness in social evolution has recently come under critical attention. These arguments are here critically analyzed, both theoretically and empirically. It is argued that when the conceptual structure of the theory of natural selection is carefully taken into account, genetic relatedness can be seen to play an indispensable role in the evolution of both facultative and advanced eusociality. Although reviewing the empirical evidence concerning the evolution of eusociality reveals that relatedness does not play a role in the initial appearance of helper phenotypes, this follows simply from the fact that natural selection - of which relatedness is a necessary component - does not play a causal role in the origin of any traits. Further, separating two logically distinct elements of causal explanation - necessity and sufficiency - explains why the debate lingers on: although relatedness plays a necessary role in the evolution of helping and advanced eusociality, relatedness alone is not sufficient for their appearance. Therefore, if the relatedness variable in a given data set is held at a uniformly high value, then it indeed may turn out that other factors occupy a more prominent role. However, this does not change the fact that high relatedness functions as a necessary background condition for the evolution of advanced eusociality.


Assuntos
Comportamento Animal/fisiologia , Aptidão Genética/fisiologia , Insetos/fisiologia , Seleção Genética/genética , Animais , Aptidão Genética/genética , Insetos/genética , Reprodução/genética , Reprodução/fisiologia , Seleção Genética/fisiologia , Comportamento Social , Sociobiologia
12.
Stud Hist Philos Biol Biomed Sci ; 77: 101187, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474495

RESUMO

In this paper, I contrast two mathematically equivalent ways of modeling the evolution of altruism, namely the classical inclusive fitness approach and a more recent, "direct fitness" approach. Though both are usually considered by evolutionists as mere different ways of representing the same causal process (i.e. that of kin selection), I argue that this consensus is misleading, for there is a fundamental ambiguity concerning the causal interpretation of the DF approach. Drawing on an analogy between the structure of inclusive fitness theory and that of causal decision theory (Stalnaker, 1972), I show that only the inclusive fitness framework can provide us with a proper, and unambiguous causal partition of the relevant variables involved in the evolution of altruism.


Assuntos
Altruísmo , Evolução Biológica , Teoria da Decisão , Aptidão Genética , Modelos Biológicos
13.
PLoS Comput Biol ; 15(8): e1006884, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31415555

RESUMO

Mutational robustness quantifies the effect of random mutations on fitness. When mutational robustness is high, most mutations do not change fitness or have only a minor effect on it. From the point of view of fitness landscapes, robust genotypes form neutral networks of almost equal fitness. Using deterministic population models it has been shown that selection favors genotypes inside such networks, which results in increased mutational robustness. Here we demonstrate that this effect is massively enhanced by recombination. Our results are based on a detailed analysis of mesa-shaped fitness landscapes, where we derive precise expressions for the dependence of the robustness on the landscape parameters for recombining and non-recombining populations. In addition, we carry out numerical simulations on different types of random holey landscapes as well as on an empirical fitness landscape. We show that the mutational robustness of a genotype generally correlates with its recombination weight, a new measure that quantifies the likelihood for the genotype to arise from recombination. We argue that the favorable effect of recombination on mutational robustness is a highly universal feature that may have played an important role in the emergence and maintenance of mechanisms of genetic exchange.


Assuntos
Aptidão Genética , Modelos Genéticos , Mutação , Recombinação Genética , Animais , Biologia Computacional , Simulação por Computador , Epistasia Genética , Evolução Molecular , Feminino , Genótipo , Masculino , Reprodução/genética , Seleção Genética
14.
Mol Cell ; 75(3): 421-425, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398322

RESUMO

Mutation rates affect both a population's present fitness and its capacity to adapt to future environmental changes. When the available genetic variability limits adaptation to environmental change, natural selection favors high mutations rates. However, constitutively high mutation rates compromise the fitness of a population in stable environments. This problem may be resolved if an increase in mutation rates is limited to times of stress, restricted to some genomic regions, and occurs only in a subpopulation of cells. Such within-population heterogeneity of mutation rates can result from genetic, environmental, and stochastic effects. The presence of subpopulations of transient mutator cells does not jeopardize the overall fitness of a population under stable environmental conditions. However, they can increase the odds of survival in changing environments because they represent reservoirs of increased genetic variability. This article presents evidence that such heterogeneity of mutation rates is more the norm than the exception.


Assuntos
Adaptação Fisiológica/genética , Aptidão Genética/genética , Taxa de Mutação , Neoplasias/genética , Dano ao DNA/genética , Reparo do DNA/genética , Farmacorresistência Bacteriana/genética , Interação Gene-Ambiente , Heterogeneidade Genética , Genética Populacional , Humanos
15.
Nat Commun ; 10(1): 3617, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399590

RESUMO

The worldwide dissemination of metallo-ß-lactamases (MBLs), mediating resistance to carbapenem antibiotics, is a major public health problem. The extent of dissemination of MBLs such as VIM-2, SPM-1 and NDM among Gram-negative pathogens cannot be explained solely based on the associated mobile genetic elements or the resistance phenotype. Here, we report that MBL host range is determined by the impact of MBL expression on bacterial fitness. The signal peptide sequence of MBLs dictates their adaptability to each host. In uncommon hosts, inefficient processing of MBLs leads to accumulation of toxic intermediates that compromises bacterial growth. This fitness cost explains the exclusion of VIM-2 and SPM-1 from Escherichia coli and Acinetobacter baumannii, and their confinement to Pseudomonas aeruginosa. By contrast, NDMs are expressed without any apparent fitness cost in different bacteria, and are secreted into outer membrane vesicles. We propose that the successful dissemination and adaptation of MBLs to different bacterial hosts depend on protein determinants that enable host adaptability and carbapenem resistance.


Assuntos
Especificidade de Hospedeiro , Metaloproteínas/genética , Metaloproteínas/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , Acinetobacter baumannii/genética , Acinetobacter baumannii/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Aptidão Genética , Interações Hospedeiro-Patógeno/genética , Humanos , Testes de Sensibilidade Microbiana , Filogenia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Análise de Sequência de DNA , beta-Lactamases/classificação
16.
PLoS Comput Biol ; 15(8): e1007333, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31469819

RESUMO

The production of anticompetitor toxins is widespread among bacteria. Because production of such toxins is costly, it is typically regulated. In particular, many toxins are produced only when the local cell density is high. It is unclear which selection pressures shaped the evolution of density-dependent regulation of toxin production. Here, we study the evolution of toxin production, resistance and the response to a cell-density cue in a model of an evolving bacterial population with spatial structure. We present results for two growth regimes: (i) an undisturbed, fixed habitat in which only small fluctuations of cell density occur, and (ii) a serial-transfer regime with large fluctuations in cell density. We find that density-dependent toxin production can evolve under both regimes. However, the selection pressures driving the evolution of regulation differ. In the fixed habitat, regulation evolves because it allows cells to produce toxin only when opportunities for reproduction are highly limited (because of a high local cell density), and the effective fitness costs of toxin production are hence low. Under serial transfers, regulation evolves because it allows cells to switch from a fast-growing non-toxic phenotype when colonising a new habitat, to a slower-growing competitive toxic phenotype when the cell density increases. Colonies of such regulating cells rapidly expand into unoccupied space because their edges consist of fast-growing, non-toxin-producing cells, but are also combative because cells at the interfaces with competing colonies do produce toxin. Because under the two growth regimes different types of regulation evolve, our results underscore the importance of growth conditions in the evolution of social behaviour in bacteria.


Assuntos
Antibiose/fisiologia , Bactérias/metabolismo , Toxinas Bacterianas/biossíntese , Modelos Biológicos , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Carga Bacteriana , Evolução Biológica , Biologia Computacional , Simulação por Computador , Ecossistema , Aptidão Genética , Genótipo , Interações Microbianas/fisiologia , Fenótipo
17.
Malar J ; 18(1): 295, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462253

RESUMO

BACKGROUND: Competitive outcomes between co-infecting malaria parasite lines can reveal fitness disparities in blood stage growth. Blood stage fitness costs often accompany the evolution of drug resistance, with the expectation that relatively fitter parasites will be more likely to spread in populations. With the recent emergence of artemisinin resistance, it is important to understand the relative competitive fitness of the metabolically active asexual blood stage parasites. Genetically distinct drug resistant parasite clones with independently evolved sets of mutations are likely to vary in asexual proliferation rate, contributing to their chance of transmission to the mosquito vector. METHODS: An optimized in vitro 96-well plate-based protocol was used to quantitatively measure-head-to-head competitive fitness during blood stage development between seven genetically distinct field isolates from a hotspot of emerging artemisinin resistance and the laboratory strain, NF54. These field isolates were isolated from patients in Southeast Asia carrying different alleles of kelch13 and included both artemisinin-sensitive and artemisinin-resistant isolates. Fluorescent labeled microsatellite markers were used to track the relative densities of each parasite throughout the co-growth period of 14-60 days. All-on-all competitions were conducted for the panel of eight parasite lines (28 pairwise competitions) to determine their quantitative competitive fitness relationships. RESULTS: Twenty-eight pairwise competitive growth outcomes allowed for an unambiguous ranking among a set of seven genetically distinct parasite lines isolated from patients in Southeast Asia displaying a range of both kelch13 alleles and clinical clearance times and a laboratory strain, NF54. This comprehensive series of assays established the growth relationships among the eight parasite lines. Interestingly, a clinically artemisinin resistant parasite line that carries the wild-type form of kelch13 outcompeted all other parasites in this study. Furthermore, a kelch13 mutant line (E252Q) was competitively more fit without drug than lines with other resistance-associated kelch13 alleles, including the C580Y allele that has expanded to high frequencies under drug pressure in Southeast Asian resistant populations. CONCLUSIONS: This optimized competitive growth assay can be employed for assessment of relative growth as an index of fitness during the asexual blood stage growth between natural lines carrying different genetic variants associated with artemisinin resistance. Improved understanding of the fitness costs of different parasites proliferating in human blood and the role different resistance mutations play in the context of specific genetic backgrounds will contribute to an understanding of the potential for specific mutations to spread in populations, with the potential to inform targeted strategies for malaria therapy.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos/genética , Evolução Molecular , Aptidão Genética , Plasmodium falciparum/crescimento & desenvolvimento , Genótipo , Técnicas de Genotipagem , Estágios do Ciclo de Vida/genética , Repetições de Microssatélites/genética , Mutação , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética
18.
PLoS Comput Biol ; 15(8): e1007246, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31374072

RESUMO

Successful prediction of the likely paths of tumor progression is valuable for diagnostic, prognostic, and treatment purposes. Cancer progression models (CPMs) use cross-sectional samples to identify restrictions in the order of accumulation of driver mutations and thus CPMs encode the paths of tumor progression. Here we analyze the performance of four CPMs to examine whether they can be used to predict the true distribution of paths of tumor progression and to estimate evolutionary unpredictability. Employing simulations we show that if fitness landscapes are single peaked (have a single fitness maximum) there is good agreement between true and predicted distributions of paths of tumor progression when sample sizes are large, but performance is poor with the currently common much smaller sample sizes. Under multi-peaked fitness landscapes (i.e., those with multiple fitness maxima), performance is poor and improves only slightly with sample size. In all cases, detection regime (when tumors are sampled) is a key determinant of performance. Estimates of evolutionary unpredictability from the best performing CPM, among the four examined, tend to overestimate the true unpredictability and the bias is affected by detection regime; CPMs could be useful for estimating upper bounds to the true evolutionary unpredictability. Analysis of twenty-two cancer data sets shows low evolutionary unpredictability for several of the data sets. But most of the predictions of paths of tumor progression are very unreliable, and unreliability increases with the number of features analyzed. Our results indicate that CPMs could be valuable tools for predicting cancer progression but that, currently, obtaining useful predictions of paths of tumor progression from CPMs is dubious, and emphasize the need for methodological work that can account for the probably multi-peaked fitness landscapes in cancer.


Assuntos
Modelos Biológicos , Neoplasias/genética , Neoplasias/patologia , Teorema de Bayes , Biologia Computacional , Simulação por Computador , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Evolução Molecular , Aptidão Genética , Genótipo , Humanos , Modelos Genéticos , Mutação , Processos Neoplásicos , Prognóstico
19.
Stud Hist Philos Biol Biomed Sci ; 76: 101188, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326324

RESUMO

This paper elaborates a general framework to make sense of teleological explanations in Darwinian evolutionary biology. It relies on an attempt to tie natural selection to a sense of optimization. First, after assessing the objections made by any attempt to view selection as a maximising process within population genetics, it understands Grafen's Formal Darwinism (FD) as a conceptual link established between population genetics and behavioral ecology's adaptationist framework (without any empirical commitments). Thus I suggest that this provides a way to make sense of teleological explanations in biology under their various modes. Then the paper criticizes two major ways of accounting for teleology: a Darwinian one, the etiological view of biological functions, and a non-Darwinian one, here labeled "intrinsic teleology" view, which covers several subtypes of accounts, including plasticity-oriented conceptions of evolution or organizational views of function. The former is centered on traits while the latter is centered on organisms; this is shown to imply that both accounts are unable to provide a systematic understanding of biological teleology. Finally the paper argues that viewing teleology as maximization of inclusive fitness along the FD lines as understood here allows one to make sense of both the design of organisms and the individual traits as adaptions. Such notion is thereby claimed to be the proper meaning of teleology in evolutionary biology, since it avoids the opposed pitfalls of etiological views and intrinsic-teleology view, while accounting for the same features as they do.


Assuntos
Evolução Biológica , Biologia/métodos , Aptidão Genética , Modelos Genéticos , Filosofia
20.
Stud Hist Philos Biol Biomed Sci ; 76: 101186, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326325

RESUMO

I distinguish two roles for a fitness concept in the context of explaining cumulative adaptive evolution: fitness as a predictor of gene frequency change, and fitness as a criterion for phenotypic improvement. Critics of inclusive fitness argue, correctly, that it is not an ideal fitness concept for the purpose of predicting gene-frequency change, since it relies on assumptions about the causal structure of social interaction that are unlikely to be exactly true in real populations, and that hold as approximations only given a specific type of weak selection. However, Hamilton took this type of weak selection, on independent grounds, to be responsible for cumulative assembly of complex adaptations. In this special context, I argue that inclusive fitness is distinctively valuable as a criterion for improvement and a standard for optimality. Yet to call inclusive fitness a criterion for improvement and a standard for optimality is not to make any claim about the frequency with which inclusive fitness optimization actually occurs in nature. This is an empirical question that cannot be settled by theory alone. I close with some reflections on the place of inclusive fitness in the long running clash between 'causalist' and 'statisticalist' conceptions of fitness.


Assuntos
Evolução Biológica , Biologia/métodos , Frequência do Gene , Aptidão Genética , Modelos Genéticos , Filosofia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA