Permanent link to this recordhttp://hdl.handle.net/20.500.12613/4202
MetadataShow full item record
AbstractBackground: Genomic sequence analyses have shown that horizontal gene transfer occurred during the origin of eukaryotes as a consequence of symbiosis. However, details of the timing and number of symbiotic events are unclear. A timescale for the early evolution of eukaryotes would help to better understand the relationship between these biological events and changes in Earth's environment, such as the rise in oxygen. We used refined methods of sequence alignment, site selection, and time estimation to address these questions with protein sequences from complete genomes of prokaryotes and eukaryotes. Results: Eukaryotes were found to evolve faster than prokaryotes, with those eukaryotes derived from eubacteria evolving faster than those derived from archaebacteria. We found an early time of divergence (∼4 billion years ago, Ga) for archaebacteria and the archaebacterial genes in eukaryotes. Our analyses support at least two horizontal gene transfer events in the origin of eukaryotes, at 2.7 Ga and 1.8 Ga. Time estimates for the origin of cyanobacteria (2.6 Ga) and the divergence of an early-branching eukaryote that lacks mitochondria (Giardia) (2.2 Ga) fall between those two events. Conclusions: We find support for two symbiotic events in the origin of eukaryotes: one premitochondrial and a later mitochondrial event. The appearance of cyanobacteria immediately prior to the earliest undisputed evidence for the presence of oxygen (2.4-2.2 Ga) suggests that the innovation of oxygenic photosynthesis had a relatively rapid impact on the environment as it set the stage for further evolution of the eukaryotic cell. © 2001 Hedges et al; licensee BioMed Central Ltd.
Citation to related workSpringer Science and Business Media LLC
Has partBMC Evolutionary Biology
ADA complianceFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact firstname.lastname@example.org
Showing items related by title, author, creator and subject.
No more business as usual: Agile and effective responses to emerging pathogen threats require open data and open analyticsBaker, Dannon; van den Beek, Marius; Blankenberg, Daniel; Bouvier, Dave; Chilton, John; Coraor, Nate; Coppens, Frederik; Eguinoa, Ignacio; Gladman, Simon; Grüning, Björn; Keener, Nicholas; Larivière, Delphine; Lonie, Andrew; Pond, Sergei; Maier, Wolfgang; Nekrutenko, Anton; Taylor, James; Weaver, Steven; 0000-0003-4817-4029; 0000-0002-6931-7191 (2020-08-13)The current state of much of the Wuhan pneumonia virus (COVID-19) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies, and requires unimpeded access to data, analysis tools, and computational infrastructure. Here we show that community efforts in developing open analytical software tools over the past ten years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all COVID-19 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and to (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.
Depletion of the RNA binding protein HNRNPD impairs homologous recombination by inhibiting DNA-end resection and inducing R-loop accumulationAlfano, L; Caporaso, A; Altieri, A; Dell'Aquila, M; Landi, C; Bini, L; Pentimalli, F; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2019-01-01)© The Author(s) 2019. DNA double strand break (DSB) repair through homologous recombination (HR) is crucial to maintain genome stability. DSB resection generates a single strand DNA intermediate, which is crucial for the HR process. We used a synthetic DNA structure, mimicking a resection intermediate, as a bait to identify proteins involved in this process. Among these, LC/MS analysis identified the RNA binding protein, HNRNPD. We found that HNRNPD binds chromatin, although this binding occurred independently of DNA damage. However, upon damage, HNRNPD re-localized to γH2Ax foci and its silencing impaired CHK1 S345 phosphorylation and the DNA end resection process. Indeed, HNRNPD silencing reduced: the ssDNA fraction upon camptothecin treatment; AsiSI-induced DSB resection; and RPA32 S4/8 phosphorylation. CRISPR/Cas9-mediated HNRNPD knockout impaired in vitro DNA resection and sensitized cells to camptothecin and olaparib treatment. We found that HNRNPD interacts with the heterogeneous nuclear ribonucleoprotein SAF-A previously associated with DNA damage repair. HNRNPD depletion resulted in an increased amount of RNA:DNA hybrids upon DNA damage. Both the expression of RNase H1 and RNA pol II inhibition recovered the ability to phosphorylate RPA32 S4/8 in HNRNPD knockout cells upon DNA damage, suggesting that RNA:DNA hybrid resolution likely rescues the defective DNA damage response of HNRNPD-depleted cells.
Genomic Instability Originates From Leukemia Stem Cells In a Mouse Model of CML-CPSkorski, Tomasz; Tsygankov, Alexander; Soprano, Kenneth J.; Liebermann, Dan A.; Shore, Scott K. (Temple University. Libraries, 2013)In chronic myelogenous leukemia (CML), activation of BCR-ABL, the product of the bcr-abl chimeric gene, leads to constitutive activation of pathways that increase genomic instability through endogenous production of reactive oxygen species (ROS) that cause oxidative DNA damage and inactivate the function of repair proteins leading to unfaithful DNA repair. If misrepaired, oxidative DNA damage, such as 8-oxoguanine (8-oxoG), may result in point mutations and/or DNA double-strand breaks (DSBs) leading to drug resistance to the BCR-ABL kinase inhibitor imatinib mesylate (IM) and accumulation of chromosomal aberrations associated with malignant CML progression from a benign chronic phase (CP) to a fatal blast phase (BP). To determine which population of CML-CP cells, leukemia stem cells (LSCs) and/or leukemia progenitor cells (LPCs), displays elevated levels of ROS and oxidative DNA damage, and whether these elevated levels of ROS and oxidative DNA damage in CML-CP subpopulations result in the accumulation of genomic instability, we employed the tetracycline-inducible SCLtTA/BCR-ABL transgenic mouse model. We showed that LSCs, including the quiescent subpopulation, but not LPCs, displayed elevated levels of ROS and oxidative DNA damage, perhaps due to deregulated expression of genes involved in ROS metabolism, resulting in genomic instability manifested by both point mutations and genetic alterations. We also examined the effect of IM on ROS, oxidative DNA damage and genomic instability displayed by CML-CP subpopulations, and determined that elevated ROS and oxidative DNA damage were not inhibited by IM in quiescent LSCs, nor was genomic instability and deregulated gene expression prevented. To explore underlying mechanisms, i.e. BCR-ABL expression levels, by which CML-CP cells accumulate genomic instability, we examined the effect of low and high BCR-ABL expression on ROS and oxidative DNA damage in BCR-ABL-transduced human CD34+ cells. We detected elevated ROS and oxidative DNA damage in high BCR-ABL-expressing CD34+ cells compared to low BCR-ABL-expressing cells. Furthermore, BCR-ABL exerted a kinase-dependent effect on ROS-dependent DNA damage. These data support the hypothesis that genomic instability may originate from LSCs, but do not exclude the potential role of LPCs, and may have important clinical implications for CML treatment since additional genetic aberrations that encode primary resistance may protect LSCs, including the quiescent subpopulation, from eradication by tyrosine kinase inhibitors (TKIs), and the continuous accumulation of genetic errors may trigger disease relapse and progression.