scholarly journals Selection Pressures on RNA Sequences and Structures

2019 ◽  
Vol 15 ◽  
pp. 117693431987191 ◽  
Author(s):  
Katja Nowick ◽  
Maria Beatriz Walter Costa ◽  
Christian Höner zu Siederdissen ◽  
Peter F Stadler
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Rna Sequences ◽  
Selection Pressures ◽  
Evolutionary Studies ◽  
Species Evolution ◽  
Selection Of

With the discovery of increasingly more functional noncoding RNAs (ncRNAs), it becomes eminent to more strongly consider them as important players during species evolution. Although tests for negative selection of ncRNAs already exist since the beginning of this century, the SSS-test is the first one for also investigating positive selection. When analyzing selection in ncRNAs, it should be taken into account that selection pressures can independently act on sequence and structure. We applied the SSS-test to explore the evolution of ncRNAs in primates and identified more than 100 long noncoding RNAs (lncRNAs) that might evolve under positive selection in humans. With this test, it is now possible to more thoroughly include ncRNAs into evolutionary studies.

scholarly journals Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Giuseppe Badalamenti ◽  
Nadia Barraco ◽  
Lorena Incorvaia ◽  
Antonio Galvano ◽  
Daniele Fanale ◽  
...  
Keyword(s):  
Potential Role ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Pcr Analysis ◽  
Tumor Aggressiveness ◽  
Mutation Status ◽  
Expression Levels ◽  
Tissue Specimens ◽  
Selection Of

Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be correlated with c-KIT mutation status. The percentage of both H19 and MALAT1 upregulation was significantly higher in patients with time to progression (TTP) < 6 months as compared to patients with TTP > 6 months. The median TTP was significantly lower in patients with both H19 and MALAT1 lncRNA upregulation as compared to those with lncRNA downregulation. These data suggest a potential role for both H19 and MALAT1 lncRNAs as prognostic biomarker for the clinical selection of the best candidate to first-line treatment with imatinib.

scholarly journals Extreme C-terminal sites are posttranslocationally glycosylated by the STT3B isoform of the OST

2013 ◽  
Vol 201 (1) ◽  
pp. 81-95 ◽  
Author(s):  
Shiteshu Shrimal ◽  
Steven F. Trueman ◽  
Reid Gilmore
Keyword(s):  
Endoplasmic Reticulum ◽  
Positive Selection ◽  
Protein C ◽  
Negative Selection ◽  
Bioinformatics Analysis ◽  
Chain Termination ◽  
Catalytic Subunits ◽  
C Terminus ◽  
Glycosylation Sites ◽  
Selection Of

Metazoan organisms assemble two isoforms of the oligosaccharyltransferase (OST) that have different catalytic subunits (STT3A or STT3B) and partially nonoverlapping roles in asparagine-linked glycosylation. The STT3A isoform of the OST is primarily responsible for co-translational glycosylation of the nascent polypeptide as it enters the lumen of the endoplasmic reticulum. The C-terminal 65–75 residues of a glycoprotein will not contact the translocation channel–associated STT3A isoform of the OST complex before chain termination. Biosynthetic pulse labeling of five human glycoproteins showed that extreme C-terminal glycosylation sites were modified by an STT3B-dependent posttranslocational mechanism. The boundary for STT3B-dependent glycosylation of C-terminal sites was determined to fall between 50 and 55 residues from the C terminus of a protein. C-terminal NXT sites were glycosylated more rapidly and efficiently than C-terminal NXS sites. Bioinformatics analysis of glycopeptide databases from metazoan organisms revealed a lower density of C-terminal acceptor sites in glycoproteins because of reduced positive selection of NXT sites and negative selection of NXS sites.

scholarly journals Enhanced positive selection of a transgenic TCR by a restriction element that does not permit negative selection

1993 ◽  
Vol 5 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Pamela S. Ohashi ◽  
Rolf M. Zinkernagel ◽  
Immanuel Leuscher ◽  
Hans Hengartner ◽  
Hanspeter Pircher
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Restriction Element ◽  
Selection Of

scholarly journals B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells

2013 ◽  
Vol 25 (4) ◽  
pp. 259-269 ◽  
Author(s):  
Tara J. Dillon ◽  
Maho Takahashi ◽  
Yanping Li ◽  
Srilatha Tavisala ◽  
Susan E. Murray ◽  
...  
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Selection Of

scholarly journals Host-Virus Arms Races Drive Elevated Adaptive Evolution in Viral Receptors

2020 ◽  
Vol 94 (16) ◽  
Author(s):  
Wenqiang Wang ◽  
Huayao Zhao ◽  
Guan-Zhu Han
Keyword(s):  
Positive Selection ◽  
Local Adaptation ◽  
Adaptive Evolution ◽  
Negative Selection ◽  
Host Cells ◽  
Human Populations ◽  
Arms Races ◽  
Selection Pressures ◽  
Selection For ◽  
Viral Receptors

ABSTRACT Viral receptors are the cell surface proteins that are hijacked by viruses to initialize their infections. Viral receptors are subject to two conflicting directional forces, namely, negative selection due to functional constraints and positive selection due to host-virus arms races. It remains largely obscure whether negative pleiotropy limits the rate of adaptation in viral receptors. Here, we perform evolutionary analyses of 96 viral receptor genes in primates and find that 41 out of 96 viral receptors experienced adaptive evolution. Many positively selected residues in viral receptors are located at the virus-receptor interfaces. Compared with control proteins, viral receptors exhibit significantly elevated rate of adaptation. Further analyses of genetic polymorphisms in human populations reveal signals of positive selection and balancing selection for 53 and 5 viral receptors, respectively. Moreover, we find that 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our findings suggest that diverse viruses, many of which have not been known to infect nonhuman primates, have maintained antagonistic associations with primates for millions of years, and the host-virus conflicts drive accelerated adaptive evolution in viral receptors. IMPORTANCE Viruses hijack cellular proteins, termed viral receptors, to assist their entry into host cells. While viral receptors experience negative selection to maintain their normal functions, they also undergo positive selection due to an everlasting evolutionary arms race between viruses and hosts. A complete picture on how viral receptors evolve under two conflicting forces is still lacking. In this study, we systematically analyzed the evolution of 96 viral receptors in primates and human populations. We found around half of viral receptors underwent adaptive evolution and exhibit significantly elevated rates of adaptation compared to control genes in primates. We also found signals of past natural selection for 58 viral receptors in human populations. Interestingly, 49 viral receptors experienced different selection pressures in different human populations, indicating that viruses represent an important driver of local adaptation in humans. Our results suggest that host-virus arms races drive accelerated adaptive evolution in viral receptors.

CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

1993 ◽  
Vol 23 (1) ◽  
pp. 212-216 ◽  
Author(s):  
Wai-Ping Fung-Leung ◽  
Valerie A. Wallace ◽  
Dawn Gray ◽  
William C. Sha ◽  
Hanspeter Pircher ◽  
...  
Keyword(s):  
T Cells ◽  
Positive Selection ◽  
Negative Selection ◽  
Selection Of

Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3550-3559 ◽  
Author(s):  
Jean-Marc Waldburger ◽  
Simona Rossi ◽  
Georg A. Hollander ◽  
Hans-Reimer Rodewald ◽  
Walter Reith ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Negative Selection ◽  
Cd4 T Cell ◽  
Thymic Epithelial Cells ◽  
Mhcii Expression ◽  
Selection Of

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4+ T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV−/− mice. Medullary thymic epithelial cells (mTECs) are also MHCII− in pIV−/− mice. Bone marrow–derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV−/− mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4+ thymocytes in pIV−/− mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV−/−mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4+T-cell population of pIV−/− mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the Vβ repertoire of the residual CD4+ T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common γ chain (CD132) or common β chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

scholarly journals T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thymic selection: requirement of calcineurin activation for thymic positive selection but not negative selection.

1995 ◽  
Vol 181 (3) ◽  
pp. 927-941 ◽  
Author(s):  
C R Wang ◽  
K Hashimoto ◽  
S Kubo ◽  
T Yokochi ◽  
M Kubo ◽  
...  
Keyword(s):  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
Intracellular Signaling ◽  
Negative Selection ◽  
Cell Receptor ◽  
Clonal Deletion ◽  
Signaling Events ◽  
Selection Of

The goal of this study was to identify the differences of intracellular signals between the processes of thymic positive and negative selection. The activation of calcineurin, a calcium- and calmodulin-dependent phosphatase, is known to be an essential event in T cell activation via the T cell receptor (TCR). The effect of FK506, an inhibitor of calcineurin activation, on positive and negative selection in CD4+CD8+ double positive (DP) thymocytes was examined in normal mice and in a TCR transgenic mouse model. In vivo FK506 treatment blocked the generation of mature TCRhighCD4+CD8- and TCRhighCD4-CD8+ thymocytes, and the induction of CD69 expression on DP thymocytes. In addition, the shutdown of recombination activating gene 1 (RAG-1) transcription and the downregulation of CD4 and CD8 expression were inhibited by FK506 treatment suggesting that the activation of calcineurin is required for the first step (or the very early intracellular signaling events) of TCR-mediated positive selection of DP thymocytes. In contrast, FK506-sensitive calcineurin activation did not appear to be required for negative selection based on the observations that negative selection of TCR alpha beta T cells in the H-2b male thymus (a negative selecting environment) was not inhibited by in vivo treatment with FK506 and that there was no rescue of the endogenous superantigen-mediated clonal deletion of V beta 6 and V beta 11 thymocytes in FK506-treated CBA/J mice. DNA fragmentation induced by TCR activation of DP thymocytes in vitro was not affected by FK506. In addition, different effects of FK506 from Cyclosporin A on the T cell development in the thymus were demonstrated. The results of this study suggest that different signaling pathways work in positive and negative selection and that there is a differential dependence on calcineurin activation in the selection processes.

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