scholarly journals Evolution of Selective RNA Processing and Stabilization operons in cellulosome-harboring Clostridium spp.

2021 ◽  
Author(s):  
Yogendra Bhaskar ◽  
Mohammadhadi Heidari B. ◽  
Chenggang Xu ◽  
Jian Xu
Keyword(s):  
Positive Selection ◽  
Rna Processing ◽  
Similar Pattern ◽  
Glycoside Hydrolase ◽  
Negative Selection ◽  
Gene Variation ◽  
Genome Wide ◽  
Operon Evolution ◽  
Clostridium Spp ◽  
Selection Of

In selective RNA processing and stabilization (SRPS) operons, the stoichiometry of encoded proteins is determined by their respective 3'-end stem-loops (SLs), yet the evolution of this mechanism remains elusive. In cellulosomal operons of Clostridium spp., we show that the SLs and their associated genes form a monogamy companionship during the operon evolution. Based on ∆G of such SLs, we propose CoSLOE (Composite SL-based Operon Evolution) model with evolutionary ratio (ER) >1 or <1 for positive or negative selection of SRPS operons. In the composite SL-∆G-based tree (CoSL-tree) of cellulosomal operons, when traversing from leafs to the root nodes, ERs reveal diversifying/positive selection towards a less efficient cellulosomal system, consistent with glycoside-hydrolase gene variation both in-operon and genome-wide. A similar pattern is followed by the ATPase operon and the majority of orthologous SRPS operons genome-wide, suggesting conservation among operons in such selection. Thus SRPS operons via their transcript-stabilizing non-coding elements are highlighting a link between operon stoichiometry and operon evolution.

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 Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever

2012 ◽  
Vol 367 (1590) ◽  
pp. 868-877 ◽  
Author(s):  
Kristian G. Andersen ◽  
Ilya Shylakhter ◽  
Shervin Tabrizi ◽  
Sharon R. Grossman ◽  
Christian T. Happi ◽  
...  
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Lassa Fever ◽  
West African ◽  
Lassa Virus ◽  
Genome Wide ◽  
African Populations ◽  
Genome Wide Data ◽  
Differential Gene ◽  
Selection Of

Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 ( IL21 ), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21 . Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit.

scholarly journals Most cancers carry a substantial deleterious load due to Hill-Robertson interference

2019 ◽  
Author(s):  
Susanne Tilk ◽  
Christina Curtis ◽  
Dmitri A Petrov ◽  
Christopher D McFarland
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Selection Model ◽  
Fitness Cost ◽  
Deleterious Mutations ◽  
Weak Selection ◽  
Selective Pressures ◽  
Mutational Burden ◽  
Genome Wide ◽  
Average Fitness

AbstractCancer genomes exhibit surprisingly weak signatures of negative selection1,2. This may be because tumors evolve under weak selective pressures (‘weak selection’) or because genome-wide linkage in cancer prevents most deleterious mutations from being removed due to Hill-Robertson interference3 (‘inefficient selection’). The weak selection model argues that most genes are only important for multicellular function and that selection acts only on a subset of essential genes. In contrast, the inefficient selection model predicts that only cancers with low mutational burdens, where linkage effects are minimal, will exhibit strong signals of negative selection against deleterious passengers and positive selection for beneficial drivers. We leverage the 10,000-fold variation in mutational burden across cancer subtypes to stratify tumors by their genome-wide mutational burden and used a normalized ratio of nonsynonymous to synonymous substitutions (dN/dS) to quantify the extent that selection varies with mutation rate. We find that appreciable negative selection (dN/dS ~ 0.4) is present in tumors with a low mutational burden, while the remaining cancers (96%) exhibit dN/dS ratios approaching 1, suggesting that the majority of tumors do not remove deleterious passengers. A parallel pattern is seen in drivers, where positive selection attenuates as the mutational burden of cancers increases. Both trends persist across tumor-types, are not exclusive to essential or housekeeping genes, are present in clonal and subclonal mutations, and persist in Copy Number Alterations. A consequence of this inability to remove deleterious passengers is that tumors with elevated mutational burdens, which are expected to harbor substantial protein folding stress, upregulate heat shock pathways. Finally, using evolutionary modeling, we find that Hill-Robertson interference alone can reproduce the patterns of attenuated selection observed in both drivers and passengers if the average fitness cost of passengers is 1.0% and the average fitness benefit of drivers is 19%. As a result, despite the weak individual fitness effects of passengers, most cancers harbor a large mutational load (median ~40% total fitness cost). Collectively, our findings suggest that the lack of observed negative selection in most tumors is not due to relaxed selective pressures, but rather the inability of selection to remove individual deleterious mutations in the presence of genome-wide linkage.

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 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

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

scholarly journals Most cancers carry a substantial deleterious load due to Hill-Robertson interference

2020 ◽  
Author(s):  
Christopher McFarland ◽  
Susanne Tilk ◽  
Christina Curtis ◽  
Dmitri Petrov
Keyword(s):  
Positive Selection ◽  
Negative Selection ◽  
Selection Model ◽  
Fitness Cost ◽  
Deleterious Mutations ◽  
Weak Selection ◽  
Selective Pressures ◽  
Mutational Burden ◽  
Genome Wide ◽  
Average Fitness

Abstract Cancer genomes exhibit surprisingly weak signatures of negative selection. This may be because tumors evolve under weak selective pressures (‘weak selection’) or because genome-wide linkage in cancer prevents most deleterious mutations from being removed due to Hill-Robertson interference3 (‘inefficient selection’). The weak selection model argues that most genes are only important for multicellular function and that selection acts only on a subset of essential genes. In contrast, the inefficient selection model predicts that only cancers with low mutational burdens, where linkage effects are minimal, will exhibit strong signals of negative selection against deleterious passengers and positive selection for beneficial drivers. We leverage the 10,000-fold variation in mutational burden across cancer subtypes to stratify tumors by their genome-wide mutational burden and used a normalized ratio of nonsynonymous to synonymous substitutions (dN/dS) to quantify the extent that selection varies with mutation rate. We find that appreciable negative selection (dN/dS ~ 0.4) is present in tumors with a low mutational burden, while the remaining cancers (96%) exhibit dN/dS ratios approaching 1, suggesting that the majority of tumors do not remove deleterious passengers. A parallel pattern is seen in drivers, where positive selection attenuates as the mutational burden of cancers increases. Both trends persist across tumor-types, are not exclusive to essential or housekeeping genes, are present in clonal and subclonal mutations, and persist in Copy Number Alterations. A consequence of this inability to remove deleterious passengers is that tumors with elevated mutational burdens, which are expected to harbor substantial protein folding stress, upregulate heat shock pathways. Finally, using evolutionary modeling, we find that Hill-Robertson interference alone can reproduce the patterns of attenuated selection observed in both drivers and passengers if the average fitness cost of passengers is 1.0% and the average fitness benefit of drivers is 19%. As a result, despite the weak individual fitness effects of passengers, most cancers harbor a large mutational load (median ~40% total fitness cost). Collectively, our findings suggest that the lack of observed negative selection in most tumors is not due to relaxed selective pressures, but rather the inability of selection to remove individual deleterious mutations in the presence of genome-wide linkage.

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