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Macromolecular function frequently requires that proteins change conformation into high-energy states1-4. However, methods for solving the structures of these functionally essential, lowly populated states are lacking. Here we develop a method for high-resolution structure determination of minorly populated states by coupling NMR spectroscopy-derived pseudocontact shifts5 (PCSs) with Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion6 (PCS-CPMG). Our approach additionally defines the corresponding kinetics and thermodynamics of high-energy excursions, thereby characterizing the entire free-energy landscape. Using a large set of simulated data for adenylate kinase (Adk), calmodulin and Src kinase, we find that high-energy PCSs accurately determine high-energy structures (with a root mean squared deviation of less than 3.5 angström). Applying our methodology to Adk during catalysis, we find that the high-energy excursion involves surprisingly small openings of the AMP and ATP lids. This previously unresolved high-energy structure solves a longstanding controversy about conformational interconversions that are rate-limiting for catalysis. Primed for either substrate binding or product release, the high-energy structure of Adk suggests a two-step mechanism combining conformational selection to this state, followed by an induced-fit step into a fully closed state for catalysis of the phosphoryl-transfer reaction. Unlike other methods for resolving high-energy states, such as cryo-electron microscopy and X-ray crystallography, our solution PCS-CPMG approach excels in cases involving domain rearrangements of smaller systems (less than 60 kDa) and populations as low as 0.5%, and enables the simultaneous determination of protein structure, kinetics and thermodynamics while proteins perform their function.
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Adenilato Quinase , Adenilato Quinase/metabolismo , Microscopia Crioeletrônica , Cristalografia por Raios X , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , TermodinâmicaRESUMO
PURPOSE OF REVIEW: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. RECENT FINDINGS: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.
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COVID-19 , Transtornos de Estresse Pós-Traumáticos , Encéfalo , Sistema Nervoso Central , Humanos , SARS-CoV-2RESUMO
INTRODUCTION: Previous research has suggested that the Amish may experience a relatively high prevalence of Parkinson's disease (PD) and/or parkinsonian motor signs. METHODS: In a large sample from the Amish community in Lancaster County, Pennsylvania, age ≥18 years, we assessed the prevalence of self-reported PD diagnosis. For those without self-reported PD diagnosis, we assessed the frequency of PD-related motor symptoms using a 9-item questionnaire that was designed by the PD Epidemiology Research Group. Lastly, we queried study participants for the presence of 2 nonmotor symptoms that have been commonly linked to PD: bowel movement frequency and daytime sleepiness. RESULTS: Among 2,025 subjects who answered the PD questionnaire, 430 were older than 60 years. Of 430 participants ≥60 years, 5 (1.2%) reported a PD diagnosis. Of those without a PD diagnosis, 10.5% reported ≥1 and 1.2% ≥ 4 motor symptoms for the 9-item PD screening questionnaire. Of the 3,789 subjects who answered the question about bowel movement frequency, 0.7% reported ≤3 bowel movements per week. Among 1,710 subjects who answered the question about daytime sleepiness, 8.1% of the participants reported "always" sleepy during the day. DISCUSSION: These data neither support a markedly higher PD prevalence in the older Lancaster Amish nor do they show dramatically higher motor and/or selected nonmotor symptoms than the general population. Future studies that employ more rigorous procedures for case identification and PD-specific preclinical symptoms/tests are needed to determine the potential differences and similarities among different Amish populations and between Amish and non-Amish populations.
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Amish , Doença de Parkinson/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Constipação Intestinal/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Pennsylvania , Projetos Piloto , Prevalência , Sonolência , Inquéritos e Questionários , Adulto JovemRESUMO
Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection. Cytoskeletal motor proteins in Porphyra are restricted to a small set of kinesins that appear to be the only universal cytoskeletal motors within the red algae. Dynein motors are absent, and most red algae, including Porphyra, lack myosin. This surprisingly minimal cytoskeleton offers a potential explanation for why red algal cells and multicellular structures are more limited in size than in most multicellular lineages. Additional discoveries further relating to the stress tolerance of bangiophytes include ancestral enzymes for sulfation of the hydrophilic galactan-rich cell wall, evidence for mannan synthesis that originated before the divergence of green and red algae, and a high capacity for nutrient uptake. Our analyses provide a comprehensive understanding of the red algae, which are both commercially important and have played a major role in the evolution of other algal groups through secondary endosymbioses.
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Citoesqueleto/genética , Evolução Molecular , Genoma de Planta/genética , Porphyra/citologia , Porphyra/genética , Actinas/genética , Sinalização do Cálcio/genética , Ciclo Celular/genética , Parede Celular/genética , Parede Celular/metabolismo , Cromatina/genética , Cinesinas/genética , FilogeniaRESUMO
Various organisations and experts have published numerous statements and recommendations regarding different aspects of sports-related concussion including definition, presentation, treatment, management and return to play guidelines. 1-7 To date, there have been no written consensus statements specific for combat sports regarding management of combatants who have suffered a concussion or for return to competition after a concussion. In combat sports, head contact is an objective of the sport itself. Accordingly, management and treatment of concussion in combat sports should, and must, be more stringent than for non-combat sports counterparts.The Association of Ringside Physicians (an international, non-profit organisation dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish management guidelines that ringside physicians, fighters, referees, trainers, promoters, sanctioning bodies and other healthcare professionals can use in the ringside setting. We also provide guidelines for the return of a combat sports athlete to competition after sustaining a concussion. This consensus statement does not address the management of moderate to severe forms of traumatic brain injury, such as intracranial bleeds, nor does it address the return to competition for combat sports athletes who have suffered such an injury. These more severe forms of brain injuries are beyond the scope of this statement. This consensus statement does not address neuroimaging guidelines in combat sports.
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Traumatismos em Atletas/terapia , Concussão Encefálica/terapia , Medicina Esportiva/métodos , Atletas , Consenso , Humanos , Médicos , Volta ao Esporte , Sociedades MédicasRESUMO
BACKGROUND: Summer/spring-type seasonal affective disorder (S-SAD) is the less common subtype of seasonal affective disorder and evidence regarding potential triggers of S-SAD is scarce. Recent reports support association of airborne-pollen with seasonal exacerbation of depression (mood seasonality) and timing of suicidal behavior. Therefore, we hypothesized that Old Order Amish (OOA) with summer/spring pattern of seasonality (abbreviated as summer pattern) and S-SAD will have significant mood worsening on high pollen days. METHODS: A seasonal pattern of mood worsening and SAD parameters were estimated using Seasonal Pattern Assessment Questionnaire (SPAQ). Age- and gender-adjusted ANCOVAs and post hoc analyses were conducted to compare mood worsening on days with high pollen counts between summer-pattern vs no-summer-pattern of mood worsening, S-SAD vs no-S-SAD, winter-pattern vs no-winter-pattern of mood worsening, and W-SAD vs no-W-SAD groups. RESULTS: The prevalence of S-SAD was 0.4%, while 4.5% of individuals had a summer pattern of mood seasonality. A statistically significant difference for mood worsening on high pollen days was observed between summer-pattern vs no-summer-pattern of mood worsening (p = 0.006). The significant association between S-SAD vs no-SAD groups (p = 0.032) for mood worsening on high pollen days did not withstand Bonferroni adjustment for multiple comparisons. No significant association was found for winter-pattern vs no-winter-pattern of mood worsening (p = 0.61) and for W-SAD vs no-W-SAD (p = 0.19) groups. CONCLUSION: Our results are consistent with previous studies implicating links between aeroallergen exposure and summer pattern of seasonality, but not the winter pattern of seasonality.
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BACKGROUND: Evidence links Toxoplasmagondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. METHODS: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. RESULTS: T. gondii seropositives reported less sleep problems (p < 0.005) and less daytime problems due to poor sleep (p < 0.005). Higher T. gondii titers were associated with longer sleep duration (p < 0.05), earlier bedtime (p< 0.005) earlier mid-sleep time (p < 0.05). CONCLUSIONS: It seems unlikely that sleep mediates the previously reported associations between T. gondii and mental illness. Future longitudinal studies with objective measures are necessary to replicate our findings.
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Red algae are the oldest identifiable multicellular eukaryotes, with a fossil record dating back more than a billion years. During that time two major rhodophyte lineages, bangiophytes and florideophytes, have evolved varied levels of morphological complexity. These two groups are distinguished, in part, by different patterns of multicellular development, with florideophytes exhibiting a far greater diversity of morphologies. Interestingly, during their long evolutionary history, there is no record of a rhodophyte achieving the kinds of cellular and tissue-specific differentiation present in other multicellular algal lineages. To date, the genetic underpinnings of unique aspects of red algal development are largely unexplored; however, they must reflect the complements and patterns of expression of key regulatory genes. Here we report comparative evolutionary and gene expression analyses of core subunits of the SWI/SNF chromatin-remodeling complex, which is implicated in cell differentiation and developmental regulation in more well studied multicellular groups. Our results suggest that a single, canonical SWI/SNF complex was present in the rhodophyte ancestor, with gene duplications and evolutionary diversification of SWI/SNF subunits accompanying the evolution of multicellularity in the common ancestor of bangiophytes and florideophytes. Differences in how SWI/SNF chromatin remodeling evolved subsequently, in particular gene losses and more rapid divergence of SWI3 and SNF5 in bangiophytes, could help to explain why they exhibit a more limited range of morphological complexity than their florideophyte cousins.
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Proteínas de Algas/genética , Montagem e Desmontagem da Cromatina , Rodófitas/genética , Transcrição Gênica , Proteínas de Algas/metabolismo , Genoma , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rodófitas/metabolismo , TranscriptomaRESUMO
In model eukaryotes, the C-terminal domain (CTD) of the largest subunit of DNA-dependent RNA polymerase II (RNAP II) is composed of tandemly repeated heptads with the consensus sequence YSPTSPS. The core motif and tandem structure generally are conserved across model taxa, including animals, yeasts and higher plants. Broader investigations revealed that CTDs of many organisms deviate substantially from this canonical structure; however, limited sampling made it difficult to determine whether disordered sequences reflect the CTD's ancestral state or degeneration from ancestral repetitive structures. Therefore, we undertook, to our knowledge, the broadest investigation to date of the evolution of the RNAP II CTD across eukaryotic diversity. Our results indicate that a tandemly repeated CTD existed in the ancestors of each major taxon, and that degeneration and reinvention of this ordered structure are common features of CTD evolution. Lineage-specific CTD modifications appear to be associated with greater developmental complexity in multicellular organisms, a pattern taken to an extreme in fungi and red algae, in which the CTD has undergone dramatic to complete alteration during the transition from unicellular to developmentally complex forms. Overall, loss and reinvention of repeats have punctuated CTD evolution, occurring independently and sometimes repeatedly in various groups.
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Evolução Molecular , Variação Genética , Filogenia , RNA Polimerase II/química , RNA Polimerase II/genética , Animais , Fungos/metabolismo , Plantas/metabolismo , Estrutura Terciária de Proteína , RNA Polimerase II/metabolismo , Sequências Repetitivas de Aminoácidos , Rodófitas/metabolismoRESUMO
Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1 ± 16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n = 280] and PHQ-2 [n = 26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p = 0.045) and current combined anhedonia and dysphoria/hopelessness (p = 0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.
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Toxoplasma gondii (T. gondii) infects central nervous tissue and is kept in relative dormancy by a healthy immune system. Sleep disturbances have been found to precipitate mental illness, suicidal behavior and car accidents, which have been previously linked to T. gondii as well. We speculated that if sleep disruption, particularly insomnia, would mediate, at least partly, the link between T. gondii infection and related behavioral dysregulation, then we would be able to identify significant associations between sleep disruption and T. gondii. The mechanisms for such an association may involve dopamine (DA) production by T. gondii, or collateral effects of immune activation necessary to keep T. gondii in check. Sleep questionnaires from 2031 Old Order Amish were analyzed in relationship to T. gondii-IgG antibodies measured by enzyme-linked immunosorbent assay (ELISA). Toxoplasma gondii seropositivity and serointensity were not associated with any of the sleep latency variables or Epworth Sleepiness Scale (ESS). A secondary analysis identified, after adjustment for age group, a statistical trend toward shorter sleep duration in seropositive men (p = 0.07). In conclusion, it is unlikely that sleep disruption mediates links between T. gondii and mental illness or behavioral dysregulation. Trending gender differences in associations between T. gondii and shorter sleep need further investigation.
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BACKGROUND: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. METHODS: We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide. RESULTS: We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls. LIMITATIONS: Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons. CONCLUSION: Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.
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Citocinas/metabolismo , Transtorno Depressivo/metabolismo , Cinurenina/metabolismo , Córtex Pré-Frontal/metabolismo , Adulto , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Reação em Cadeia da Polimerase , Córtex Pré-Frontal/patologia , RNA Mensageiro/metabolismoRESUMO
The idea that evolutionary models should minimize plastid endosymbioses has dominated thinking about the history of eukaryotic photosynthesis. Although a reasonable starting point, this framework has not gained support from observed patterns of algal and plant evolution, and can be an obstacle to fully understanding the modern distribution of plastids. Empirical data indicate that plastid losses are extremely uncommon, that major changes in plastid biochemistry/architecture are evidence of an endosymbiotic event, and that comparable selection pressures can lead to remarkable convergences in algae with different endosymbiotic origins. Such empirically based generalizations can provide a more realistic philosophical framework for interpreting complex and often contradictory results from phylogenomic investigations of algal evolution.
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BACKGROUND: The acquisition of complex transcriptional regulatory abilities and epigenetic machinery facilitated the transition of the ancestor of apicomplexans from a free-living organism to an obligate parasite. The ability to control sophisticated gene expression patterns enabled these ancient organisms to evolve several differentiated forms, invade multiple hosts and evade host immunity. How these abilities were acquired remains an outstanding question in protistan biology. RESULTS: In this work, we study SET domain bearing genes that are implicated in mediating immune evasion, invasion and cytoadhesion pathways of modern apicomplexans, including malaria parasites. We provide the first conclusive evidence of a horizontal gene transfer of a Histone H4 Lysine 20 (H4K20) modifier, Set8, from an animal host to the ancestor of apicomplexans. Set8 is known to contribute to the coordinated expression of genes involved in immune evasion in modern apicomplexans. We also show the likely transfer of a H3K36 methyltransferase (Ashr3 from plants), possibly derived from algal endosymbionts. These transfers appear to date to the transition from free-living organisms to parasitism and coincide with the proposed horizontal acquisition of cytoadhesion domains, the O-glycosyltransferase that modifies these domains, and the primary family of transcription factors found in apicomplexan parasites. Notably, phylogenetic support for these conclusions is robust and the genes clearly are dissimilar to SET sequences found in the closely related parasite Perkinsus marinus, and in ciliates, the nearest free-living organisms with complete genome sequences available. CONCLUSIONS: Animal and plant sources of epigenetic machinery provide new insights into the evolution of parasitism in apicomplexans. Along with the horizontal transfer of cytoadhesive domains, O-linked glycosylation and key transcription factors, the acquisition of SET domain methyltransferases marks a key transitional event in the evolution to parasitism in this important protozoan lineage.
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Apicomplexa/genética , Evolução Biológica , Transferência Genética Horizontal , Plasmodium falciparum/genética , Sequência de Aminoácidos , Animais , Teorema de Bayes , DNA de Protozoário/genética , Dictyostelium/genética , Histona Metiltransferases , Histona-Lisina N-Metiltransferase/genética , Funções Verossimilhança , Nematoides/genética , Parasitos/genética , Filogenia , Análise de Sequência de DNARESUMO
Community colleges are frequently an affordable, accessible entrance to a Science, Technology, Engineering, and Mathematics (STEM) education and career, but the transition from a 2-year program to a 4-year institution can be tumultuous. In this mixed-methods study, we explore the experiences of transfer and prospective transfer students. Through surveys and interviews, we identify the challenges faced by and the supports desired by biology transfer students. We describe how community college students perceive their introductory biology courses, and we compare the biology identity and self-efficacy of these students to peers at a 4-year institution. Students expressed uncertainty about what to expect from the transfer experience, and they benefitted from interventions that made the university experience more concrete or clarified their expectations. We found that community college students are just as interested in biology as peers at a 4-year university, but they are significantly less likely to believe that others recognize them as "biology people" and report less self-efficacy regarding biology courses. Students felt particularly well-prepared for transfer after community college biology courses they described as "rigorous" and "demanding," especially because students expressed that the community college environment helped support them through the challenges of higher education.
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BACKGROUND: Increasing evidence suggests that conditions with decreased morning and increased evening light exposure, including shift work, daylight-saving time, and eveningness, are associated with elevated mortality and suicide risk. Given that the alignment between the astronomical, biological, and social time varies across a time zone, with later-shifted daylight exposure in the western partition, we hypothesized that western time zone partitions would have higher suicide rates than eastern partitions. METHODS: United States (U.S.) county-level suicide and demographic data, from 2010 to 2018, were obtained from a Centers for Disease Control database. Using longitude and latitude, counties were sorted into the western, middle, or eastern partition of their respective time zones, as well as the northern and southern halves of the U.S. Linear regressions were used to estimate the associations between suicide rates and time zone partitions, adjusting for gender, race, ethnicity, age group, and unemployment rates. RESULTS: Data were available for 2872 counties. Across the U.S., western partitions had statistically significantly higher rates of suicide compared to eastern partitions and averaged up to two additional yearly deaths per 100,000 people (p < .001). LIMITATIONS: Ecological design and limited adjustment for socioeconomic factors. CONCLUSIONS: To our knowledge, this is the first study of the relationship between longitude-based time zone partitions and suicide. The results were consistent with the hypothesized elevated suicide rates in the western partitions, and concordant with previous reports on cancer mortality and transportation fatalities. The next step is to retest the hypothesis with individual-level data, accounting for latitude, photoperiodic changes, daylight-saving time, geoclimatic variables, physical and mental health indicators, as well as socioeconomic adversity and protection.
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Suicídio , Humanos , Estados Unidos/epidemiologia , Fatores Socioeconômicos , Etnicidade , Saúde MentalRESUMO
Somatolactin (SL) and SL receptor (SLR) belong to the growth hormone and cytokine type I receptor superfamilies, respectively. However, further research is required to define the duplications and functions of SL and its receptors in basal vertebrates including environmental background color adaptation in fish. In the present study, we cloned and sequenced SL and its putative receptor (SLR), classified and compared the sequences phylogenetically, and determined SL and SLR mRNA expression levels during long-term background color exposure in Cichlasoma dimerus, a freshwater South American cichlid. Our results show that C. dimerus SL and SLR share high sequence similarity with homologous from other perciform fish. Phylogenetic analysis indicates that C. dimerus SL belongs to the SLα clade sub-group. C. dimerus SLR is clearly a member of the GHR1 receptor subgroup, which includes the experimentally validated SLR from salmonids. Higher transcript levels of SLα in the pituitary and SLR in the epidermis and dermis cells of fish scales were observed in fish following long-term black background color exposure compared to those exposed to a white background. A higher number of melanophores was also observed in fish exposed for 10days to a black background compared to those exposed to a white background. These changes were concomitant to differences in SL or SLR transcript levels found in fish exposed to these two different background colors. Our results suggest, for the first time, that SLR is expressed in fish scales, and that there is an increase in SL in the pituitary and the putative SLR in likely target cells, i.e., melanophores, in long-term black background exposure in C. dimerus.
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Aclimatação/genética , Ciclídeos/genética , Proteínas de Peixes/genética , Glicoproteínas/genética , Hormônios Hipofisários/genética , Receptores do Hormônio Hipofisário/genética , Receptores da Somatotropina/genética , Pigmentação da Pele/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Ciclídeos/fisiologia , Clonagem Molecular , Cor , Meio Ambiente , Proteínas de Peixes/fisiologia , Glicoproteínas/fisiologia , Melanóforos/fisiologia , Dados de Sequência Molecular , Filogenia , Hormônios Hipofisários/fisiologia , RNA Mensageiro/metabolismo , Receptores do Hormônio Hipofisário/fisiologia , Receptores da Somatotropina/fisiologiaRESUMO
Genetic reprogramming of differentiated cells is studied broadly in multicellular Viridiplantae as an adaptation to herbivory or damage; however, mechanisms underlying cell development and redifferentiation are largely unknown in red algae, their nearest multicellular relatives. Here we investgate cell reprogramming in the widely cultivated, edible seaweed Neopyropia yezoesis ("nori"), where vegetative cells in wounded blades differentiate and release as large numbers of asexual spores. Based upon physiological changes and transcriptomic dynamics after wound stress in N. yezoensis and its congener Neoporphyra haitanensis, another cultivar that does not differentiate spores after wounding, we propose a three-phase model of wound-induced spore development in N. yezoensis. In Phase I, propagation of ROS by RBOH and SOD elicites systematic transduction of the wound signal, while Ca2+ dependent signaling induces cell reprogramming. In Phase II, a TOR signaling pathway and regulation of cyclin and CDK genes result in cell divisions that spread inward from the wound edge. Once sporangia form, Phase III involves expression of proteins required for spore maturation and cell wall softening. Our analyses not only provide the first model for core molecular processes controlling cellular reprogramming in rhodophytes, but also have practical implications for achieving greater control over seeding in commercial nori farming.
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A growing number of phylogenomic investigations from diverse eukaryotes are examining conflicts among gene trees as evidence of horizontal gene transfer. If multiple foreign genes from the same eukaryotic lineage are found in a given genome, it is increasingly interpreted as concerted gene transfers during a cryptic endosymbiosis in the organism's evolutionary past, also known as "endosymbiotic gene transfer" or EGT. A number of provocative hypotheses of lost or serially replaced endosymbionts have been advanced; to date, however, these inferences largely have been post-hoc interpretations of genomic-wide conflicts among gene trees. With data sets as large and complex as eukaryotic genome sequences, it is critical to examine alternative explanations for intra-genome phylogenetic conflicts, particularly how much conflicting signal is expected from directional biases and statistical noise. The availability of genome-level data both permits and necessitates phylogenomics that test explicit, a priori predictions of horizontal gene transfer, using rigorous statistical methods and clearly defined experimental controls.
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Biologia Computacional/métodos , Evolução Molecular , Transferência Genética Horizontal/genética , Genoma/genética , Modelos Genéticos , Filogenia , Simbiose/genética , Genômica/métodosRESUMO
With a simple tandem iterated sequence, the carboxyl terminal domain (CTD) of eukaryotic RNA polymerase II (RNAP II) serves as the central coordinator of mRNA synthesis by harmonizing a diversity of sequential interactions with transcription and processing factors. Despite intense research interest, many key questions regarding functional and evolutionary constraints on the CTD remain unanswered; for example, what selects for the canonical heptad sequence, its tandem array across organismal diversity, and constant CTD length within given species and finally and how a sequence-identical, repetitive structure can orchestrate a diversity of simultaneous and sequential, stage-dependent interactions with both modifying enzymes and binding partners? Here we examine comparative sequence evolution of 58 RNAP II CTDs from diverse taxa representing all six major eukaryotic supergroups and employ integrated evolutionary genetic, biochemical, and biophysical analyses of the yeast CTD to further clarify how this repetitive sequence must be organized for optimal RNAP II function. We find that the CTD is composed of indivisible and independent functional units that span diheptapeptides and not only a flexible conformation around each unit but also an elastic overall structure is required. More remarkably, optimal CTD function always is achieved at approximately wild-type CTD length rather than number of functional units, regardless of the characteristics of the sequence present. Our combined observations lead us to advance an updated CTD working model, in which functional, and therefore, evolutionary constraints require a flexible CTD conformation determined by the CTD sequence and tandem register to accommodate the diversity of CTD-protein interactions and a specific CTD length rather than number of functional units to correctly order and organize global CTD-protein interactions. Patterns of conservation of these features across evolutionary diversity have important implications for comparative RNAP II function in eukaryotes and can more clearly direct specific research on CTD function in currently understudied organisms.