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1.
Cell ; 185(24): 4541-4559.e23, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36334588

RESUMO

The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical stimuli applied to the skin, large-scale in vivo electrophysiological recordings, and genetic manipulations, here we show that neurons in the mouse spinal cord DH receive convergent inputs from both low- and high-threshold mechanoreceptor subtypes and exhibit one of six functionally distinct mechanical response profiles. Genetic disruption of DH feedforward or feedback inhibitory motifs, comprised of interneurons with distinct mechanical response profiles, revealed an extensively interconnected DH network that enables dynamic, flexible tuning of postsynaptic dorsal column (PSDC) output neurons and dictates how neurons in the primary somatosensory cortex respond to touch. Thus, mechanoreceptor subtype convergence and non-linear transformations at the earliest stage of the somatosensory hierarchy shape how touch of the skin is represented in the brain.


Assuntos
Mecanorreceptores , Corno Dorsal da Medula Espinal , Animais , Camundongos , Tato/fisiologia , Interneurônios , Encéfalo , Medula Espinal
2.
Cell ; 174(3): 505-520, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30053424

RESUMO

Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the corresponding datasets at the protein complex and functional pathway level. Here, we describe one path forward-an initiative aimed at mapping the physical and genetic interaction networks of these conditions and then using these maps to connect the genomic data to neurobiology and, ultimately, the clinic. These efforts will include a team of geneticists, structural biologists, neurobiologists, systems biologists, and clinicians, leveraging a wide array of experimental approaches and creating a collaborative infrastructure necessary for long-term investigation. This initiative will ultimately intersect with parallel studies that focus on other diseases, as there is a significant overlap with genes implicated in cancer, infectious disease, and congenital heart defects.


Assuntos
Mapeamento Cromossômico/métodos , Transtornos do Neurodesenvolvimento/genética , Biologia de Sistemas/métodos , Redes Reguladoras de Genes/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , Neurobiologia/métodos , Neuropsiquiatria
3.
Cell ; 172(1-2): 121-134.e14, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29307490

RESUMO

Chronic Pseudomonas aeruginosa infections evade antibiotic therapy and are associated with mortality in cystic fibrosis (CF) patients. We find that in vitro resistance evolution of P. aeruginosa toward clinically relevant antibiotics leads to phenotypic convergence toward distinct states. These states are associated with collateral sensitivity toward several antibiotic classes and encoded by mutations in antibiotic resistance genes, including transcriptional regulator nfxB. Longitudinal analysis of isolates from CF patients reveals similar and defined phenotypic states, which are associated with extinction of specific sub-lineages in patients. In-depth investigation of chronic P. aeruginosa populations in a CF patient during antibiotic therapy revealed dramatic genotypic and phenotypic convergence. Notably, fluoroquinolone-resistant subpopulations harboring nfxB mutations were eradicated by antibiotic therapy as predicted by our in vitro data. This study supports the hypothesis that antibiotic treatment of chronic infections can be optimized by targeting phenotypic states associated with specific mutations to improve treatment success in chronic infections.


Assuntos
Fibrose Cística/microbiologia , Farmacorresistência Bacteriana , Evolução Molecular , Fenótipo , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Fibrose Cística/complicações , Proteínas de Ligação a DNA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Seleção Genética , Fatores de Transcrição/genética
4.
Mol Cell ; 74(2): 231-244.e9, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30850330

RESUMO

The convergence of two DNA replication forks creates unique problems during DNA replication termination. In E. coli and SV40, the release of torsional strain by type II topoisomerases is critical for converging replisomes to complete DNA synthesis, but the pathways that mediate fork convergence in eukaryotes are unknown. We studied the convergence of reconstituted yeast replication forks that include all core replisome components and both type I and type II topoisomerases. We found that most converging forks stall at a very late stage, indicating a role for additional factors. We showed that the Pif1 and Rrm3 DNA helicases promote efficient fork convergence and completion of DNA synthesis, even in the absence of type II topoisomerase. Furthermore, Rrm3 and Pif1 are also important for termination of plasmid DNA replication in vivo. These findings identify a eukaryotic pathway for DNA replication termination that is distinct from previously characterized prokaryotic mechanisms.


Assuntos
DNA Helicases/genética , Replicação do DNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , DNA Topoisomerases/genética , Escherichia coli/genética , Eucariotos/genética , Instabilidade Genômica , Plasmídeos/genética
5.
Proc Natl Acad Sci U S A ; 121(17): e2305517121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38621135

RESUMO

Growing crops in more diverse crop systems (i.e., intercropping) is one way to produce food more sustainably. Even though intercropping, compared to average monocultures, is generally more productive, the full yield potential of intercropping might not yet have been achieved as modern crop cultivars are bred to be grown in monoculture. Breeding plants for more familiarity in mixtures, i.e., plants that are adapted to more diverse communities (i.e., adaptation) or even to coexist with each other (i.e., coadaptation) might have the potential to sustainably enhance productivity. In this study, the productivity benefits of familiarity through evolutionary adaptation and coevolutionary coadaptation were disentangled in a crop system through an extensive common garden experiment. Furthermore, evolutionary and coevolutionary effects on species-level and community-level productivity were linked to corresponding changes in functional traits. We found evidence for higher productivity and trait convergence with increasing familiarity with the plant communities. Furthermore, our results provide evidence for the coevolution of plants in mixtures leading to higher productivity of coadapted species. However, with the functional traits measured in our study, we could not fully explain the productivity benefits found upon coevolution. Our study investigated coevolution among randomly interacting plants and was able to demonstrate that coadaptation through coevolution of coexisting species in mixtures occurs and promotes ecosystem functioning (i.e., higher productivity). This result is particularly relevant for the diversification of agricultural and forest ecosystems, demonstrating the added value of artificially selecting plants for the communities they are familiar with.


Assuntos
Ecossistema , Melhoramento Vegetal , Agricultura/métodos , Produtos Agrícolas , Evolução Biológica
6.
Proc Natl Acad Sci U S A ; 120(1): e2203724120, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36577073

RESUMO

Multitrait adaptive evolution is shaped by factors such as phylogenetic and functional constraints as well as the intensity and direction of selection. The tempo and mode of such multitrait evolution can differentially impact the assembly of biological communities. Batesian mimicry, in which undefended prey gain a fitness advantage by evolving a resemblance to aposematic models, involves adaptive evolution of multiple traits such as color patterns and flight morphology. To elucidate the evolutionary mechanisms of such multitrait adaptations, we evaluated the tempo and mode of adaptive convergence in flight morphology and color patterns in mimetic butterfly communities. We found that compared with Batesian mimics or nonmimetic sister species, models showed significantly faster rates of aposematic trait evolution, creating adaptive peaks for mimicry. At the community level, the degree of mimetic resemblance between mimics and models was positively correlated with the rate of character evolution, but independent of phylogenetic relatedness. Monomorphic mimics and female-limited mimics converged on the color patterns of models to a similar degree, showing that there were no constraints on mimetic trait evolution with respect to sex-specific selections. Convergence was driven by the greater lability of color patterns, which evolved at significantly faster rates than the phylogenetically conserved flight morphological traits, indicating that the two traits evolve under differential selection pressures and/or functional and genetic constraints. These community-wide patterns show that during the assembly of a community, the tempo of adaptive evolution is nonlinear, and specific to the underlying functional relationships and key traits that define the community.


Assuntos
Mimetismo Biológico , Borboletas , Animais , Feminino , Masculino , Evolução Biológica , Biota , Borboletas/genética , Filogenia , Comportamento Predatório
7.
Proc Natl Acad Sci U S A ; 120(43): e2307340120, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37844245

RESUMO

Echolocation, the detection of objects by means of sound waves, has evolved independently in diverse animals. Echolocators include not only mammals such as toothed whales and yangochiropteran and rhinolophoid bats but also Rousettus fruit bats, as well as two bird lineages, oilbirds and swiftlets. In whales and yangochiropteran and rhinolophoid bats, positive selection and molecular convergence has been documented in key hearing-related genes, such as prestin (SLC26A5), but few studies have examined these loci in other echolocators. Here, we examine patterns of selection and convergence in echolocation-related genes in echolocating birds and Rousettus bats. Fewer of these loci were under selection in Rousettus or birds compared with classically recognized echolocators, and elevated convergence (compared to outgroups) was not evident across this gene set. In certain genes, however, we detected convergent substitutions with potential functional relevance, including convergence between Rousettus and classic echolocators in prestin at a site known to affect hair cell electromotility. We also detected convergence between Yangochiroptera, Rhinolophidea, and oilbirds in TMC1, an important mechanosensory transduction channel in vertebrate hair cells, and observed an amino acid change at the same site within the pore domain. Our results suggest that although most proteins implicated in echolocation in specialized mammals may not have been recruited in birds or Rousettus fruit bats, certain hearing-related loci may have undergone convergent functional changes. Investigating adaptations in diverse echolocators will deepen our understanding of this unusual sensory modality.


Assuntos
Quirópteros , Ecolocação , Animais , Quirópteros/fisiologia , Filogenia , Evolução Molecular , Mamíferos/genética , Audição/genética , Baleias/fisiologia , Aves/genética , Ecolocação/fisiologia
8.
Proc Natl Acad Sci U S A ; 120(47): e2217064120, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38033310

RESUMO

The intertropical convergence zone (ITCZ) plays a key role in regulating tropical hydroclimate and global water cycle through changes in its convection strength, latitudinal position, and width. The long-term variability of the ITCZ, along with the corresponding driving mechanisms, however, remains obscure, mainly because it is difficult to separate different ITCZ variables in paleoclimate proxy records. Here, we report a speleothem oxygen isotope (δ18O) record from southwestern Sulawesi, Indonesia, and compile it with other speleothem records from the Maritime Continent. Using the spatial gradient of speleothem δ18O along a transect across the ITCZ, we constrain ITCZ variabilities over the Maritime Continent during the past 30,000 y. We find that ITCZ convection strength overall intensified from the last glacial period to the Holocene, following changes in climate boundary conditions. The mean position of the regional ITCZ has moved latitudinally no more than 3° in the past 30,000 y, consistent with the deduction from the atmospheric energy framework. However, different from modern observations and model simulations for future warming, the ITCZ appeared narrower during both the late Holocene and most part of the last glacial period, and its expansion occurred during Heinrich stadials and the early-to-mid Holocene. We also find that during the last glacial and deglacial period, prominent millennial-scale ITCZ changes were closely tied to the variability of the Atlantic meridional overturning circulation (AMOC), whereas during the Holocene, they were predominantly modulated by the long-term variability of the Walker circulation.

9.
Proc Natl Acad Sci U S A ; 120(31): e2302930120, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37490538

RESUMO

This paper is concerned with the problem of reconstructing an unknown rank-one matrix with prior structural information from noisy observations. While computing the Bayes optimal estimator is intractable in general due to the requirement of computing high-dimensional integrations/summations, Approximate Message Passing (AMP) emerges as an efficient first-order method to approximate the Bayes optimal estimator. However, the theoretical underpinnings of AMP remain largely unavailable when it starts from random initialization, a scheme of critical practical utility. Focusing on a prototypical model called [Formula: see text] synchronization, we characterize the finite-sample dynamics of AMP from random initialization, uncovering its rapid global convergence. Our theory-which is nonasymptotic in nature-in this model unveils the non-necessity of a careful initialization for the success of AMP.

10.
Proc Natl Acad Sci U S A ; 119(27): e2202862119, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35776547

RESUMO

Identifying the genetic basis of repeatedly evolved traits provides a way to reconstruct their evolutionary history and ultimately investigate the predictability of evolution. Here, we focus on the oldfield mouse (Peromyscus polionotus), which occurs in the southeastern United States, where it exhibits considerable color variation. Dorsal coats range from dark brown in mainland mice to near white in mice inhabiting sandy beaches; this light pelage has evolved independently on Florida's Gulf and Atlantic coasts as camouflage from predators. To facilitate genomic analyses, we first generated a chromosome-level genome assembly of Peromyscus polionotus subgriseus. Next, in a uniquely variable mainland population (Peromyscus polionotus albifrons), we scored 23 pigment traits and performed targeted resequencing in 168 mice. We find that pigment variation is strongly associated with an ∼2-kb region ∼5 kb upstream of the Agouti signaling protein coding region. Using a reporter-gene assay, we demonstrate that this regulatory region contains an enhancer that drives expression in the dermis of mouse embryos during the establishment of pigment prepatterns. Moreover, extended tracts of homozygosity in this Agouti region indicate that the light allele experienced recent and strong positive selection. Notably, this same light allele appears fixed in both Gulf and Atlantic coast beach mice, despite these populations being separated by >1,000 km. Together, our results suggest that this identified Agouti enhancer allele has been maintained in mainland populations as standing genetic variation and from there, has spread to and been selected in two independent beach mouse lineages, thereby facilitating their rapid and parallel evolution.


Assuntos
Proteína Agouti Sinalizadora , Evolução Biológica , Elementos Facilitadores Genéticos , Peromyscus , Pigmentação da Pele , Proteína Agouti Sinalizadora/metabolismo , Alelos , Animais , Genes Reporter , Peromyscus/genética , Peromyscus/fisiologia , Pigmentação da Pele/genética
11.
Proc Natl Acad Sci U S A ; 119(17): e2120015119, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35446705

RESUMO

Uncertainty about the influence of anthropogenic radiative forcing on the position and strength of convective rainfall in the Intertropical Convergence Zone (ITCZ) inhibits our ability to project future tropical hydroclimate change in a warmer world. Paleoclimatic and modeling data inform on the timescales and mechanisms of ITCZ variability; yet a comprehensive, long-term perspective remains elusive. Here, we quantify the evolution of neotropical hydroclimate over the preindustrial past millennium (850 to 1850 CE) using a synthesis of 48 paleo-records, accounting for uncertainties in paleo-archive age models. We show that an interhemispheric pattern of precipitation antiphasing occurred on multicentury timescales in response to changes in natural radiative forcing. The conventionally defined "Little Ice Age" (1450 to 1850 CE) was marked by a clear shift toward wetter conditions in the southern neotropics and a less distinct and spatiotemporally complex transition toward drier conditions in the northern neotropics. This pattern of hydroclimatic change is consistent with results from climate model simulations indicating that a relative cooling of the Northern Hemisphere caused a southward shift in the thermal equator across the Atlantic basin and a southerly displacement of the ITCZ in the tropical Americas, with volcanic forcing as the principal driver. These findings are at odds with proxy-based reconstructions of ITCZ behavior in the western Pacific basin, where changes in ITCZ width and intensity, rather than mean position, appear to have driven hydroclimate transitions over the last millennium. This reinforces the idea that ITCZ responses to external forcing are region specific, complicating projections of the tropical precipitation response to global warming.

12.
Proc Natl Acad Sci U S A ; 119(49): e2207754119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442126

RESUMO

Millions of people across the world live off-grid not by choice but because they live in rural areas, have low income, and have no political clout. Delivering sustainable energy solutions to such a substantial amount of the world's population requires more than a technological fix; it requires leveraging the knowledge of underserved populations working together with a transdisciplinary team to find holistically derived solutions. Our original research has resulted in an innovative Convergence Framework integrating the fields of engineering, social sciences, and communication, and is based on working together with communities and other stakeholders to address the challenges posed by delivering clean energy solutions. In this paper, we discuss the evolution of this Framework and illustrate how this Framework is being operationalized in our on-going research project, cocreating hybrid renewable energy systems for off-grid communities in the Brazilian Amazon. The research shows how this Framework can address clean energy transitions, strengthen emerging industries at local level, and foster Global North-South scholarly collaborations. We do so by the integration of social science and engineering and by focusing on community engagement, energy justice, and governance for underserved communities. Further, this solution-driven Framework leads to the emergence of unique approaches that advance scientific knowledge, while at the same time addressing community needs.


Assuntos
Sistemas Computacionais , Energia Renovável , Humanos , Engenharia , Tecnologia , Altruísmo
13.
Proc Natl Acad Sci U S A ; 119(39): e2205914119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36122242

RESUMO

Conformist and anticonformist transmission of dichotomous cultural traits (i.e., traits with two variants) have been studied both experimentally, in many species, and theoretically, with mathematical models. Signatures of types of conformity to polychotomous traits (with more than two variants; e.g., baby names and syllables in bird song) have been inferred from population-level data, but there are few models that include individual-level biases among more than two discrete variants. We generalize the standard dichotomous trait conformity model by Boyd and Richerson to incorporate [Formula: see text] role models and [Formula: see text] variants. Our analysis shows that in the case of [Formula: see text] role models, under anticonformity, the central polymorphic equilibrium [Formula: see text] is globally stable, whereas under conformity, if initially the frequencies of [Formula: see text] variants are all equal to the maximum variant frequency in the population, there is global convergence to an equilibrium in which the frequencies of these variants are all [Formula: see text] and all other variants are absent. With a general number n of role models, the same result holds with conformity, whereas under anticonformity, global convergence is not guaranteed, and there may be stable frequency cycles or chaos. If both conformity and anticonformity occur for different configurations of variants among the n role models, a variety of novel polymorphic equilibria may exist and be stable. Future empirical studies may use this formulation to directly quantify an individual's level of (anti)conformist bias to a polychotomous trait.


Assuntos
Modelos Teóricos , Fenótipo , Cultura
14.
Proc Natl Acad Sci U S A ; 119(15): e2109370119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35385351

RESUMO

Collateral sensitivity is an evolutionary trade-off whereby acquisition of the adaptive phenotype of resistance to an antibiotic leads to the nonadaptive increased susceptibility to another. The feasibility of harnessing such a trade-off to design evolutionary-based approaches for treating bacterial infections has been studied using model strains. However, clinical application of collateral sensitivity requires its conservation among strains presenting different mutational backgrounds. Particularly relevant is studying collateral sensitivity robustness of already-antibiotic-resistant mutants when challenged with a new antimicrobial, a common situation in clinics that has hardly been addressed. We submitted a set of diverse Pseudomonas aeruginosa antibiotic-resistant mutants to short-term evolution in the presence of different antimicrobials. Ciprofloxacin selects different clinically relevant resistance mutations in the preexisting resistant mutants, which gave rise to the same, robust, collateral sensitivity to aztreonam and tobramycin. We then experimentally determined that alternation of ciprofloxacin with aztreonam is more efficient than ciprofloxacin­tobramycin alternation in driving the extinction of the analyzed antibiotic-resistant mutants. Also, we show that the combinations ciprofloxacin­aztreonam or ciprofloxacin­tobramycin are the most effective strategies for eliminating the tested P. aeruginosa antibiotic-resistant mutants. These findings support that the identification of conserved collateral sensitivity patterns may guide the design of evolution-based strategies to treat bacterial infections, including those due to antibiotic-resistant mutants. Besides, this is an example of phenotypic convergence in the absence of parallel evolution that, beyond the antibiotic-resistance field, could facilitate the understanding of evolution processes, where the selective forces giving rise to new, not clearly adaptive phenotypes remain unclear.


Assuntos
Antibacterianos , Ciprofloxacina , Sensibilidade Colateral a Medicamentos , Farmacorresistência Bacteriana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Sensibilidade Colateral a Medicamentos/genética , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética
15.
J Infect Dis ; 230(1): 161-171, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052723

RESUMO

BACKGROUND: Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from classical bovine spongiform encephalopathy (C-BSE) may copropagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. METHODS: To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. RESULTS: No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, 1 isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. CONCLUSIONS: The results obtained suggest a low zoonotic potential for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.


Assuntos
Encéfalo , Síndrome de Creutzfeldt-Jakob , Cabras , Camundongos Transgênicos , Príons , Scrapie , Zoonoses , Animais , Síndrome de Creutzfeldt-Jakob/transmissão , Síndrome de Creutzfeldt-Jakob/patologia , Síndrome de Creutzfeldt-Jakob/metabolismo , Humanos , Scrapie/transmissão , Scrapie/patologia , Camundongos , Zoonoses/transmissão , Encéfalo/patologia , Encéfalo/metabolismo , Ovinos , Bovinos , Príons/metabolismo , Fenótipo , Baço/patologia , Encefalopatia Espongiforme Bovina/transmissão , Encefalopatia Espongiforme Bovina/patologia , Encefalopatia Espongiforme Bovina/metabolismo , Doenças das Cabras/transmissão , Doenças das Cabras/patologia , Modelos Animais de Doenças
16.
J Infect Dis ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38401890

RESUMO

BACKGROUND: Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from bovine spongiform encephalopathy (C-BSE) may co-propagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. METHODS: To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. RESULTS: No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, one isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. CONCLUSIONS: The results obtained suggest a low the zoonotic for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.

17.
Mol Biol Evol ; 40(2)2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36738166

RESUMO

New mutations and standing genetic variations contribute significantly to repeated phenotypic evolution in sticklebacks. However, less is known about the role of introgression in this process. We analyzed taxonomically and geographically comprehensive genomic data from Pungitius sticklebacks to decipher the extent of introgression and its consequences for the diversification of this genus. Our results demonstrate that introgression is more prevalent than suggested by earlier studies. Although gene flow was generally bidirectional, it was often asymmetric and left unequal genomic signatures in hybridizing species, which might, at least partly, be due to biased hybridization and/or population size differences. In several cases, introgression of variants from one species to another was accompanied by transitions of pelvic and/or lateral plate structures-important diagnostic traits in Pungitius systematics-and frequently left signatures of adaptation in the core gene regulatory networks of armor trait development. This finding suggests that introgression has been an important source of genetic variation and enabled phenotypic convergence among Pungitius sticklebacks. The results highlight the importance of introgression of genetic variation as a source of adaptive variation underlying key ecological and taxonomic traits. Taken together, our study indicates that introgression-driven convergence likely explains the long-standing challenges in resolving the taxonomy and systematics of this small but phenotypically highly diverse group of fish.


Assuntos
Smegmamorpha , Animais , Smegmamorpha/genética , Peixes , Mutação , Fenótipo , Adaptação Fisiológica
18.
Mol Biol Evol ; 40(4)2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36929911

RESUMO

Critical mitochondrial functions, including cellular respiration, rely on frequently interacting components expressed from both the mitochondrial and nuclear genomes. The fitness of eukaryotic organisms depends on a tight collaboration between both genomes. In the face of an elevated rate of evolution in mtDNA, current models predict that the maintenance of mitonuclear compatibility relies on compensatory evolution of the nuclear genome. Mitonuclear interactions would therefore exert an influence on evolutionary trajectories. One prediction from this model is that the same nuclear genome evolving with different mitochondrial haplotypes would follow distinct molecular paths toward higher fitness. To test this prediction, we submitted 1,344 populations derived from 7 mitonuclear genotypes of Saccharomyces cerevisiae to >300 generations of experimental evolution in conditions that either select for a mitochondrial function or do not strictly require respiration for survival. Performing high-throughput phenotyping and whole-genome sequencing on independently evolved individuals, we identified numerous examples of gene-level evolutionary convergence among populations with the same mitonuclear background. Phenotypic and genotypic data on strains derived from this evolution experiment identify the nuclear genome and the environment as the main determinants of evolutionary divergence, but also show a modulating role for the mitochondrial genome exerted both directly and via interactions with the two other components. We finally recapitulated a subset of prominent loss-of-function alleles in the ancestral backgrounds and confirmed a generalized pattern of mitonuclear-specific and highly epistatic fitness effects. Together, these results demonstrate how mitonuclear interactions can dictate evolutionary divergence of populations with identical starting nuclear genotypes.


Assuntos
DNA Mitocondrial , Genoma Mitocondrial , DNA Mitocondrial/genética , Mitocôndrias/genética , Eucariotos/genética , Genótipo , Núcleo Celular/genética
19.
Mol Biol Evol ; 40(6): msad121, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37325551

RESUMO

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.


Assuntos
Carbonato de Cálcio , Juglandaceae , Cálcio , Especiação Genética , Genômica
20.
Mol Biol Evol ; 40(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37216901

RESUMO

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.


Assuntos
Carbonato de Cálcio , Juglandaceae , Ásia Oriental , Cálcio , Especiação Genética , Genômica , Juglandaceae/genética , Juglandaceae/fisiologia
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