scholarly journals Globins in the marine Annelid Platynereis dumerilii shed new light on hemoglobin evolution in Bilaterians

2019 ◽  
Author(s):  
Solène Song ◽  
Viktor Starunov ◽  
Xavier Bailly ◽  
Christine Ruta ◽  
Pierre Kerner ◽  
...  

AbstractBackgroundHow vascular systems and their respiratory pigments evolved is still debated. While many animals present a vascular system, hemoglobin exists as a blood pigment only in a few groups (Vertebrates, Annelids, a few Arthropod and Mollusk species). Hemoglobins are formed of globin sub-units, belonging to multigene families, in various multimeric assemblages. It was so far unclear whether hemoglobin families from different Bilaterian groups had a common origin.ResultsTo unravel globin evolution in Bilaterians, we studied the marine Annelid Platynereis dumerilii, a species with a slow evolving genome. Platynereis exhibits a closed vascular system filled with extracellular hemoglobin. Platynereis genome and transcriptomes reveal a family of 19 globins, nine of which are predicted to be extracellular. Extracellular globins are produced by specialized cells lining the vessels of the segmental appendages of the worm, serving as gills, and thus likely participate in the assembly of the giant hexagonal bilayer hemoglobin of the worm. Extracellular globin mRNAs are absent in smaller juvenile, accumulate considerably in growing and more active worms and peak in swarming adults, as the need for O2 culminates. Next, we conducted a Metazoan-wide phylogenetic analysis of globins using data from complete genomes. We establish that five globin genes (stem globins) were present in the last common ancestor of Bilaterians. Based on these results, we propose a new nomenclature of globins, with five clades. All five ancestral stem-globin clades are retained in some Spiralians, while some clades disappeared early in Deuterostome and Ecdysozoan evolution. All known Bilaterian blood globin families are grouped in a single clade (clade I) together with intracellular globins of Bilaterians devoid of red blood.ConclusionsWe uncover a complex “pre-blood” evolution of globins, with an early gene radiation in ancestral Bilaterians. Circulating hemoglobins in various bilaterian groups evolved convergently, presumably in correlation with animal size and activity. However, all hemoglobins derive from a clade I globin, or cytoglobin, probably involved in intracellular O2 transit and regulation (clade I). The Annelid Platynereis is remarkable in having a large family of extracellular blood globins, while retaining all clades of ancestral Bilaterian globins.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Solène Song ◽  
Viktor Starunov ◽  
Xavier Bailly ◽  
Christine Ruta ◽  
Pierre Kerner ◽  
...  

Abstract Background How vascular systems and their respiratory pigments evolved is still debated. While many animals present a vascular system, hemoglobin exists as a blood pigment only in a few groups (vertebrates, annelids, a few arthropod and mollusk species). Hemoglobins are formed of globin sub-units, belonging to multigene families, in various multimeric assemblages. It was so far unclear whether hemoglobin families from different bilaterian groups had a common origin. Results To unravel globin evolution in bilaterians, we studied the marine annelid Platynereis dumerilii, a species with a slow evolving genome. Platynereis exhibits a closed vascular system filled with extracellular hemoglobin. Platynereis genome and transcriptomes reveal a family of 19 globins, nine of which are predicted to be extracellular. Extracellular globins are produced by specialized cells lining the vessels of the segmental appendages of the worm, serving as gills, and thus likely participate in the assembly of a previously characterized annelid-specific giant hemoglobin. Extracellular globin mRNAs are absent in smaller juveniles, accumulate considerably in growing and more active worms and peak in swarming adults, as the need for O2 culminates. Next, we conducted a metazoan-wide phylogenetic analysis of globins using data from complete genomes. We establish that five globin genes (stem globins) were present in the last common ancestor of bilaterians. Based on these results, we propose a new nomenclature of globins, with five clades. All five ancestral stem-globin clades are retained in some spiralians, while some clades disappeared early in deuterostome and ecdysozoan evolution. All known bilaterian blood globin families are grouped in a single clade (clade I) together with intracellular globins of bilaterians devoid of red blood. Conclusions We uncover a complex “pre-blood” evolution of globins, with an early gene radiation in ancestral bilaterians. Circulating hemoglobins in various bilaterian groups evolved convergently, presumably in correlation with animal size and activity. However, all hemoglobins derive from a clade I globin, or cytoglobin, probably involved in intracellular O2 transit and regulation. The annelid Platynereis is remarkable in having a large family of extracellular blood globins, while retaining all clades of ancestral bilaterian globins.


Energies ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3676
Author(s):  
Paul Nduhuura ◽  
Matthias Garschagen ◽  
Abdellatif Zerga

Many developing countries in Africa face a “double tragedy” when it comes to electrification. Electricity access rates are low, while those who have access to electricity face frequent outages. There are ongoing efforts aimed at increasing access to electricity on the continent. However, the need to improve the reliability of electricity supply receives limited attention. Unreliable electricity impacts users by limiting electricity utilization and the benefits that should accrue from having an electricity connection. Using data from 496 household survey questionnaires, this study examines the impacts of electricity outages in urban households in Accra, Ghana. The study applies correlation and regression analyses to identify which household characteristics are associated with or predict households reporting outage impacts. Outages were found to impact household safety/security, access to food, and access to social services and were found to cause appliance damage as well. Factors that are significantly correlated with reporting certain outage impacts include respondent’s annual income and employment status, frequency of electricity outages, and household size. Significant predictors of reporting outage impacts are socioeconomic disadvantage, high exposure to outages, and living in a large family setting. The study’s findings underscore the need for interventions to eliminate, or at least minimize, electricity supply interruptions in developing countries if sustainable social and economic development is to be achieved.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Elisabeth A. Rosenthal ◽  
David R. Crosslin ◽  
Adam S. Gordon ◽  
David S. Carrell ◽  
Ian B. Stanaway ◽  
...  

Abstract Background Elevated triglycerides (TG) are associated with, and may be causal for, cardiovascular disease (CVD), and co-morbidities such as type II diabetes and metabolic syndrome. Pathogenic variants in APOA5 and APOC3 as well as risk SNVs in other genes [APOE (rs429358, rs7412), APOA1/C3/A4/A5 gene cluster (rs964184), INSR (rs7248104), CETP (rs7205804), GCKR (rs1260326)] have been shown to affect TG levels. Knowledge of genetic causes for elevated TG may lead to early intervention and targeted treatment for CVD. We previously identified linkage and association of a rare, highly conserved missense variant in SLC25A40, rs762174003, with hypertriglyceridemia (HTG) in a single large family, and replicated this association with rare, highly conserved missense variants in a European American and African American sample. Methods Here, we analyzed a longitudinal mixed-ancestry cohort (European, African and Asian ancestry, N = 8966) from the Electronic Medical Record and Genomics (eMERGE) Network. We tested associations between median TG and the genes of interest, using linear regression, adjusting for sex, median age, median BMI, and the first two principal components of ancestry. Results We replicated the association between TG and APOC3, APOA5, and risk variation at APOE, APOA1/C3/A4/A5 gene cluster, and GCKR. We failed to replicate the association between rare, highly conserved variation at SLC25A40 and TG, as well as for risk variation at INSR and CETP. Conclusions Analysis using data from electronic health records presents challenges that need to be overcome. Although large amounts of genotype data is becoming increasingly accessible, usable phenotype data can be challenging to obtain. We were able to replicate known, strong associations, but were unable to replicate moderate associations due to the limited sample size and missing drug information.


2020 ◽  
Vol 42 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Megan Burley ◽  
Sally Roberts ◽  
Joanna L. Parish

AbstractHuman papillomaviruses (HPV) are a large family of viruses which contain a circular, double-stranded DNA genome of approximately 8000 base pairs. The viral DNA is chromatinized by the recruitment of cellular histones which are subject to host cell–mediated post-translational epigenetic modification recognized as an important mechanism of virus transcription regulation. The HPV life cycle is dependent on the terminal differentiation of the target cell within epithelia—the keratinocyte. The virus life cycle begins in the undifferentiated basal compartment of epithelia where the viral chromatin is maintained in an epigenetically repressed state, stabilized by distal chromatin interactions between the viral enhancer and early gene region. Migration of the infected keratinocyte towards the surface of the epithelium induces cellular differentiation which disrupts chromatin looping and stimulates epigenetic remodelling of the viral chromatin. These epigenetic changes result in enhanced virus transcription and activation of the virus late promoter facilitating transcription of the viral capsid proteins. In this review article, we discuss the complexity of virus- and host-cell-mediated epigenetic regulation of virus transcription with a specific focus on differentiation-dependent remodelling of viral chromatin during the HPV life cycle.


Paleobiology ◽  
2010 ◽  
Vol 36 (1) ◽  
pp. 16-31 ◽  
Author(s):  
Matthew M. Hedman

This paper presents a method for constraining the age of a clade with the ages of the earliest fossil specimens in that clade's outgroups. Given a sufficiently deep, robust, well-resolved, and stratigraphically consistent cladogram, this method can yield useful age constraints even in the absence of specific information about the fossil preservation and recovery rates of individual taxa. The algorithm is applied to simulated data sets to demonstrate that this method can yield robust constraints of clade ages if there are sufficient fossil outgroups available and if there is a finite chance that additional outgroups may be discovered in the future. Finally, the technique is applied to actual fossil data to explore the origin of modern placental mammals. Using data from recently published cladograms, this method indicates that if all Mesozoic eutherians are regarded as outgroups of Placentalia, then the last common ancestor of modern placental mammals and their Cenozoic allies lived between 65 and 88–98 million years ago, depending on the assumed cladogram and the number of outgroups included in the analysis.


BMC Biology ◽  
2008 ◽  
Vol 6 (1) ◽  
Author(s):  
Vidushi S Patel ◽  
Steven JB Cooper ◽  
Janine E Deakin ◽  
Bob Fulton ◽  
Tina Graves ◽  
...  

1994 ◽  
Vol 179 (2) ◽  
pp. 733-738 ◽  
Author(s):  
S Ponnazhagan ◽  
M L Nallari ◽  
A Srivastava

We sought to investigate the usefulness of the adeno-associated virus 2 (AAV)-based vectors to suppress the excess production of the human alpha-globin gene product towards developing a treatment modality for beta-thalassemia since accumulation of free alpha-globin reduces the lifespan of red blood cells in these patients. We constructed recombinant AAV virions containing the human alpha-globin gene sequences in antisense orientation driven by the herpesvirus thymidine kinase (TK) promoter, the SV40 early gene promoter, and the human alpha-globin gene promoter, respectively, as well as a bacterial gene for resistance to neomycin (neoR) as a selectable marker. These recombinant virions were used to infect a human erythroleukemia cell line (K562) that express high levels of alpha-globin mRNA. Clonal populations of neoR cells were obtained after selection with the drug G418, a neomycin analogue. Total genomic DNA samples isolated from these cells were analyzed on Southern blots to document stable integration of the transduced neo and alpha-globin genes. Total cellular RNA samples isolated from mock-infected and recombinant virus-infected cultures were also analyzed by Northern blots. Whereas the TK promoter-driven antisense alpha-globin sequences showed no inhibition of expression of the endogenous alpha-globin gene, the SV40 promoter and the alpha-globin gene promoter-driven antisense alpha-globin sequences suppressed the expression of this constitutively over-expressed gene by approximately 29 and 91%, respectively, at the transcriptional level. These studies suggest the feasibility of utilizing the AAV-based antisense gene transfer approach in the potential treatment of beta-thalassemia.


2020 ◽  
Author(s):  
Anabelle Planques ◽  
Pierre Kerner ◽  
Laure Ferry ◽  
Christoph Grunau ◽  
Eve Gazave ◽  
...  

ABSTRACTBackgroundMethylation of cytosines in DNA (5mC methylation) is a major epigenetic modification that modulates gene expression and is important for embryonic development and cell reprogramming in vertebrates. In mammals, 5mC methylation in promoter regions is linked to transcriptional repression. Transcription regulation by 5mC methylation notably involves the Nucleosome Remodeling and Deacetylase complex (NuRD complex) which bridges DNA methylation and histone modifications. Less is known about roles and mechanisms of 5mC methylation in non-vertebrate animals. In this paper, we study 5mC methylation in the marine annelid worm Platynereis dumerilii, an emerging evolutionary and developmental biology model capable of regenerating the posterior part of its body upon amputation. The regenerated region includes both differentiated structures and a growth zone consisting of stem cells required for the continuous growth of the worm.ResultsUsing in silico and experimental approaches, we show that P. dumerilii displays a high level of DNA methylation comparable to that of mammalian somatic cells. 5mC methylation in P. dumerilii is dynamic along the life cycle of the animal and markedly decreases at the transition between larval to post-larval stages. We identify a full repertoire of mainly singlecopy genes encoding the machinery associated to 5mC methylation or members of the NuRD complex in P. dumerilii and show, through phylogenetic analyses, that this repertoire is close to the one inferred for the last common ancestor of bilaterians. These genes are dynamically expressed during P. dumerilii development, growth and regeneration. Treatment with the DNA hypomethylating agent Decitabine, impairs P. dumerilii larval development and regeneration, and has long-term effects on post-regenerative growth by affecting the functionality of stem cells of the growth zone.ConclusionsOur data indicate high-level of 5mC methylation in the annelid P. dumerilii, highlighting that this feature is not specific to vertebrates in the bilaterian clade. Analysis of DNA methylation levels and machinery gene expression during development and regeneration, as well as the use of a chemical inhibitor of DNA methylation, suggest an involvement of 5mC methylation in P. dumerilii development, regeneration and stem cell-based post-regenerative growth. We also present data indicating that P. dumerilii constitutes a promising model to study biological roles and mechanisms of DNA methylation in non-vertebrate bilaterians and to provide new knowledge about evolution of the functions of this key epigenetic modification in bilaterian animals.


2017 ◽  
Author(s):  
Takaho Tsuchiya ◽  
Masashi Fujii ◽  
Naoki Matsuda ◽  
Katsuyuki Kunida ◽  
Shinsuke Uda ◽  
...  

SUMMARYCells decode information of signaling activation at a scale of tens of minutes by downstream gene expression with a scale of hours to days, leading to cell fate decisions such as cell differentiation. However, no system identification method with such different time scales exists. Here we used compressed sensing technology and developed a system identification method using data of different time scales by recovering signals of missing time points. We measured phosphorylation of ERK and CREB, immediate early gene expression products, and mRNAs of decoder genes for neurite elongation in PC12 cell differentiation and performed system identification, revealing the input–output relationships between signaling and gene expression with sensitivity such as graded or switch-like response and with time delay and gain, representing signal transfer efficiency. We predicted and validated the identified system using pharmacological perturbation. Thus, we provide a versatile method for system identification using data with different time scales.HighlightsWe developed a system identification method using compressed sensing.This method allowed us to find a pathway using data of different time scales.We identified a selective signaling-decoding system by gene expression.We validated the identified system by pharmacological perturbation.eTOC BlurbWe describe a system identification method of molecular networks with different time-scale data using a signal recovery technique in compressed sensing.


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