The Selection-Mutation-Drift Theory of Synonymous Codon Usage
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Translation Readthrough Mitigation Joshua A
LETTER doi:10.1038/nature18308 Translation readthrough mitigation Joshua A. Arribere1, Elif S. Cenik1, Nimit Jain2, Gaelen T. Hess3, Cameron H. Lee3, Michael C. Bassik3 & Andrew Z. Fire1,3 A fraction of ribosomes engaged in translation will fail to into the 3′ UTR can confer substantial loss of protein expression for at terminate when reaching a stop codon, yielding nascent proteins least these three 3′ UTRs in C. elegans. inappropriately extended on their C termini. Although such To test whether translation into 3′ UTRs could confer a loss of extended proteins can interfere with normal cellular processes, protein expression more generally, a two-fluorescent-reporter system known mechanisms of translational surveillance1 are insufficient to with each fluorophore transgene containing an identical 3′ UTR was protect cells from potential dominant consequences. Here, through used. Nine genes were chosen to reflect a variety of functions and a combination of transgenics and CRISPR–Cas9 gene editing in expression levels: rps-17 (small ribosomal subunit component), r74.6 Caenorhabditis elegans, we demonstrate a consistent ability of cells (dom34/pelota release factor homologue), hlh-1 (muscle transcription to block accumulation of C-terminal-extended proteins that result factor), eef-1A.1 (also known as eft-3, translation elongation factor), from failure to terminate at stop codons. Sequences encoded by myo-2 (a pharyngeal myosin), mut-16 (involved in gene/transposon the 3′ untranslated region (UTR) were sufficient to lower protein silencing), bar-1 (a beta catenin), daf-6 (involved in amphid mor- levels. Measurements of mRNA levels and translation suggested a phogenesis), and alr-1 (neuronal transcription factor). -
Journals of Interest - Mathematics and Science Education
Page 1 2/17/17Confidential Page 1 2/17/17Created by Office 2004 Test Drive UserMacintosh HD:Users:iMac3:Desktop:crmse stuff:Journals:Journals_Dec_16.docxCRMSE Journal Review May 2008 Journals of Interest - Mathematics and Science Education December 2016 TABLE OF CONTENTS Journal ................................................................................................... Page Educational Researcher……………………………………………………………………2 Volume 45, Issue 9 ............................................................................................................ 2 Educational Studies of Mathematics……………………………………………………....3 Volume 94, Issue 1, Pgs 1-116………………………………………………………...….3 Mathematical Thinking and Learning ………………………………………………….....4 Volume 19, Issue 1 ............................................................................................................ 4 Journal of Research in Science Teaching………………………………………......….….5 Volume 53, Issue 10………………………………………………………..……...……...5 International Journal of Science Education………………………………….............………..…6 Volume 38, Issue 15 .......................................................................................................... 6 Volume 38, Issue 16………………………………………………………...……….……7 Volume 38, Issue 17………………………………………………………………..….….8 Science Education…………………………………………………………………….…..9 Volume 101, Issue 1…………………………………………………………………………………9 Journal of College Science Teaching…………………………………………………….10 Volume 46, Issue 3………………………………………………………………………10 International Journal of Mathematical Education in Science -
From So Simple a Beginning... the Expansion of Evolutionary Thought
From So Simple A Beginning... The Expansion Of Evolutionary Thought #1 #2 From So Simple A Beginning... The Expansion Of Evolutionary Thought Compiled and Edited by T N C Vidya #3 All rights reserved. No parts of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior permission of the publisher. c Indian Academy of Sciences 2019 Reproduced from Resonance–journal of science education Published by Indian Academy of Sciences Production Team: Geetha Sugumaran, Pushpavathi R and Srimathi M Reformatted by : Sriranga Digital Software Technologies Private Limited, Srirangapatna. Printed at: Lotus Printers Pvt. Ltd., Bengaluru #4 Foreword The Masterclass series of eBooks brings together pedagogical articles on single broad top- ics taken from Resonance, the Journal of Science Education, that has been published monthly by the Indian Academy of Sciences since January 1996. Primarily directed at students and teachers at the undergraduate level, the journal has brought out a wide spectrum of articles in a range of scientific disciplines. Articles in the journal are written in a style that makes them accessible to readers from diverse backgrounds, and in addition, they provide a useful source of instruction that is not always available in textbooks. The sixth book in the series, ‘From So Simple A Beginning... The Expansion Of Evolu- tionary Thought’, is a collection of Resonance articles about scientists who made major con- tributions to the development of evolutionary biology, starting with Charles Darwin himself, collated and edited by Prof. T. N. C. -
Non-Synonymous to Synonymous Substitutions Suggest That Orthologs Tend to Keep Their Functions, While Paralogs Are a Source of Functional Novelty
bioRxiv preprint doi: https://doi.org/10.1101/354704; this version posted July 23, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty Mario Esposito1, Gabriel Moreno-Hagelsieb1,* 1 Dept of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada N2L 3C5 * [email protected] Abstract Because orthologs diverge after speciation events, and paralogs after gene duplication, it is expected that orthologs should tend to keep their functions, while paralogs have been proposed as a source of new functions. This does not mean that paralogs should diverge much more than orthologs, but it certainly means that, if there is a difference, then orthologs should be more functionally stable. Since protein functional divergence follows from non-synonymous substitutions, here we present an analysis based on the ratio of non-synonymous to synonymous substitutions (dN=dS). The results showed orthologs to have noticeable and statistically significant lower values of dN=dS than paralogs, not only confirming that orthologs keep their functions better, butalso suggesting that paralogs are a readily source of functional novelty. Author summary Homologs are characters diverging from a common ancestor, with orthologs being homologs diverging after a speciation event, and paralogs diverging after a duplication event. Given those definitions, orthologs are expected to preserve their ancestral function, while paralogs have been proposed as potential sources of functional novelty. -
Unbiased Estimate of Synonymous and Non-Synonymous Substitution Rates with Non-Stationary Base Composition
Manuscript submitted as an article for the methods section of MBE bioRxiv preprint doi: https://doi.org/10.1101/124925; this version posted April 6, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Unbiased estimate of synonymous and non-synonymous substitution rates with non-stationary base composition Laurent Gu´eguen∗ and Laurent Duret Laboratoire de Biologie et Biom´etrie Evolutive´ CNRS UMR 5558 {Universit´eClaude Bernard Lyon 1 { Universit´ede Lyon 43, bd du 11 novembre 1918,69622 VILLEURBANNE cedex ∗ [email protected] Abstract The measure of synonymous and non-synonymous substitution rates (dS and dN) is useful for assessing selection operating on protein sequences or for investigating mutational processes dN affecting genomes. In particular, the ratio dS is expected to be a good proxy of !, the probability of fixation of non-synonymous mutations relative to that of neutral mutations. Standard methods for estimating dN, dS or ! rely on the assumption that the base composition of sequences is at the equilibrium of the evolutionary process. In many clades, this assumption of stationarity is in fact incorrect, and we show here through simulations and through analyses of empirical data that non-stationarity biases the estimate of dN, dS and !. We show that the bias in the estimate of ! can be fixed by explicitly considering non-stationarity in the modeling of codon evolution, in a maximum likelihood framework. -
Manx Shearwater Chicks; Seasonal, Parental, and Genetic Influences On
The Condor 88:324-327 0 The Cooper Ornithological Society 1986 MANX SHEARWATER CHICKS: SEASONAL, PARENTAL, AND GENETIC INFLUENCES ON THE CHICK’S AGE AND WEIGHT AT FLEDGING’ M. DE L. BROOKED ZoologyDepartment, Edward Grey Institute, South Parks Road, Oxford OX1 3PS, United Kingdom Abstract. Manx Shearwater(Pu@zuspujinus) pairs on Skokholm Island, Wales, typically breed together over several seasons,rearing one chick per year. There is a seasonal decline of chick fledgingweight. Even after correction for this decline, pairs tend to rear chicksthat are consistently heavier or lighter than predicted on the basis of the chick’s hatching date. These deviations may reflect pair quality. Weight and hatching date of a chick are not correlated with age of fledging. However, fledging agesof full siblingsshow significantlyless variation than thoseof nonsiblings.The characterappears highly heritable, with a heritability value around 0.84. This is the first study to addressthe extent to which the fledging age of wild birds is genetically determined. Key words: Manx Shearwater;Puffinus puffinus;fledging age; heritability. INTRODUCTION Jones 1974) and laying date (Van Noordwijk There is apparent variation in the extent to et al. 1980). On the whole, “characters with which the age of fledging in birds mirrors en- the lowest heritabilities are those most closely vironmental circumstances.In certain species, connected with reproductive fitness,while the such as Audubon’s Shearwater (Pujinus Iher- characters with the highest heritabilities are minieri)(Harris 1969)and the Common Swift those that might be . the least important as (&us apus) (Lack 1956) age of fledging is determinants of natural fitness” (Falconer highly variable. -
2015 Annual Report
2015 ANNUAL REPORT VICTOR MATOS VAZQUEZ ADRIAN MATRAM JASON LEWIS MATSON MATTHEW MATSON SCOTT P MATSON MICHAEL A MATTEO SPENCER W MATTERS JASON P MATTHES JEFF ALLEN MATTHES JUSTIN MATTHES SUPPLE MATTHEW BILLY GENE MATTHEWS JR BLAIN MATTHEWS BOBBY N MATTHEWS BRIAN K MATTHEWS CHRISTOPHER SCOTT MATTHEWS DAMON A MATTHEWS DAVID MATTHEWS DENNIS MATTHEWS EUGENE MATTHEWS JAMES B MATTHEWS JONATHAN H MATTHEWS KARL MATTHEWS KENNETH E MATTHEWS MARK R MATTHEWS MARY C MATTHEWS MICHAEL D MATTHEWS MICHAEL E MATTHEWS PAUL MATTHEWS RAY E MATTHEWS JR RHONDA MATTHEWS ROBERT A MATTHEWS RYAN S MATTHEWS STEPHANIE R MATTHEWS TERESA A MATTHEWS TERRY MATTHEWS TRACY MATTHEWS MITCHELL D MATTINGLY KYLE MATTINSON JOHN MATTOCKS JEFFERY A MATTOX JEFFERY ALLEN MATTOX II JOSHUA JDM MATTSON KAM MATTU JOSEPH J MATUSKA TAMMY MATUSZAK MANUEL MATUTE BACHES JOSEPH MAUGERI BRUCE MAUGHAN GAYLEN C MAUGHAN JAYDEN MAUGHAN JORDAN R MAUGHAN THOMAS J MAUK ANDREW FERRELL MAULDIN ARTHUR L MAULDIN CHELSI MAULDIN MICHAEL MAULDIN KYLIE MAUNDRELL RANDY K MAURER TOBIAS MAURICE MARIBEL MAURICIO ANGELINE MAURO DAVID L MAUSEHUND KEVIN A MAVIS ANTHONY D MAXWELL CAMERON MAXWELL COLTON D MAXWELL DAVIS MAXWELL ERIC L MAXWELL JAMES TONY MAXWELL KIM MAXWELL MICHAEL W MAXWELL RODNEY MAXWELL CRAIG C MAY CRAIG M MAY GORDON D MAY JAMES A MAY JEDIDIAH E MAY JEREMY M MAY JOSEPH CHRISTOPHER MAY JUSTIN MAY KELVIN MAY KENNETH D MAY MARK E MAY MICHEAL T MAY SCOTT A MAY WILLIE D MAY DANIEL MAYA DONALD GENE MAYBERRY MARLON C MAYBERRY CLAYTON TYLER MAYER JOHN MAYER JOHN ZACHARY MAYER TROY MAYER JULIAN L MAYERS -
The KA /KS Ratio Test for Assessing the Protein
Downloaded from genome.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Methods The KA/KS Ratio Test for Assessing the Protein-Coding Potential of Genomic Regions: An Empirical and Simulation Study Anton Nekrutenko, Kateryna D. Makova, and Wen-Hsiung Li1 Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA Comparative genomics is a simple, powerful way to increase the accuracy of gene prediction. In this study, we show the utility of a simple test for the identification of protein-coding exons using human/mouse sequence comparisons. The test takes advantage of the fact that in the vast majority of coding regions, synonymous substitutions (KS) occur much more frequently than nonsynonymous ones (KA) and uses the KA/KS ratio as the criterion. We show the following: (1) most of the human and mouse exons are sufficiently long and have a suitable degree of sequence divergence for the test to perform reliably; (2) the test is suited for the identification of long exons and single exon genes, which are difficult to predict by current methods; (3) the test has a false-negative rate, lower than most of current gene prediction methods and a false-positive rate lower than all current methods; (4) the test has been automated and can be used in combination with other existing gene-prediction methods. Although computational gene prediction has made much test), which is described below. Nucleotide substitutions in progress over the last decade, its reliability remains a challeng- protein-coding regions are divided into two classes, ones that ing problem. -
John Maynard Smith Archive (1948-2004) (Add MS 86569-86840) Table of Contents
British Library: Western Manuscripts John Maynard Smith Archive (1948-2004) (Add MS 86569-86840) Table of Contents John Maynard Smith Archive (1948–2004) Key Details........................................................................................................................................ 1 Arrangement..................................................................................................................................... 2 Provenance........................................................................................................................................ 2 Add MS 86569–86574 Reprints and copies of articles and book chapters by John Maynard Smith (1952–2003)...................................................................................................................................... 3 Add MS 86575–86596 Correspondence files, F–Z (1975–1991).............................................................. 5 Add MS 86597–86830 Subject files (1948–2003).................................................................................. 18 Add MS 86831–86835 Notebooks and plant lists (1973–2003)............................................................... 223 Add MS 86836–86837 Lecture notes ([c 1990–c 1999])........................................................................ 226 Add MS 86838–86839 Artefacts and books (1983–2001)....................................................................... 227 Add MS 86840 Annotations and manuscripts with offprints received by John Maynard Smith (1952?–2003)................................................................................................................................... -
Molecular Phylogeny and Evolution
Molecular Phylogeny and Evolution 10 – 14 February 2020 Juan I. MONTOYA BURGOS Lab of Molecular Phylogeny and Evolution in Vertebrates Title of the course: Molecular Phylogeny and Molecular Evolution Evolutionary relationships among organisms = tree topology A better understanding of molecular evolution improves: First phylogenetic methods did not - topology and branch length make use of models of molecular reconstruction (=phylogenetic tree) evolution (UPGMA, Maximum Parsimony) Better phylogenetic trees improve: - the understanding of evolutionary processes => Models of molecular evolution Lab of Molecular Phylogeny and Evolution in Vertebrates 1 Why should we care about phylogenies? Are you using phylogenetics ? Lab of Molecular Phylogeny and Evolution in Vertebrates Current phylogenetic methods allow: - reconstruction of evolutionary relationships But also the analysis of: Gene/genome duplication Recombination Evolutionary rates Divergence time among lineages Selective pressure Demography Biodiversity Genetic variability Conservation Biogeography Spread of contagious disease Discovery of biomedical compounds Adaptive evolution Biomonitoring Protein-protein co-evolution And more …. Lab of Molecular Phylogeny and Evolution in Vertebrates 2 Phylogenetic analyses: many uses Understanding evolutionary relationships Determining the closest extant relative to tetrapods Amemiya et al., 2013. The African coelacanth genome provides insights into tetrapod evolution. Nature 496. Lab of Molecular Phylogeny and Evolution in Vertebrates Phylogenetic -
Role of Mrna Structure in the Control of Protein Folding Guilhem Faure, Aleksey Y
10898–10911 Nucleic Acids Research, 2016, Vol. 44, No. 22 Published online 27 July 2016 doi: 10.1093/nar/gkw671 Role of mRNA structure in the control of protein folding Guilhem Faure, Aleksey Y. Ogurtsov, Svetlana A. Shabalina and Eugene V. Koonin* National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA Received May 03, 2016; Revised July 12, 2016; Accepted July 14, 2016 ABSTRACT speed and fidelity of translation. Although much attention had focused on the initiation step as a major determinant Specific structures in mRNA modulate translation of translation rate, multiple studies over nearly two decades rate and thus can affect protein folding. Using the have made it clear that elongation also plays an important protein structures from two eukaryotes and three role in the regulation of translation and co-translational prokaryotes, we explore the connections between protein folding (1–3). In particular, it has been shown that the protein compactness, inferred from solvent ac- in some proteins, ␣-helices and -strands are flanked by cessibility, and mRNA structure, inferred from mRNA strong signals in the mRNA sequence (4,5). Different pro- folding energy (G). In both prokaryotes and eukary- tein structures have been reported to correlate with distinct otes, the G value of the most stable 30 nucleotide patterns of synonymous codon usage in the respective mR- segment of the mRNA (Gmin) strongly, positively NAs (6,7). More generally, it has been proposed that dif- correlates with protein solvent accessibility. Thus, ferent protein secondary structures are encoded by mRNA sequences with distinct properties. -
Does Mrna Structure Contain Genetic Information for Regulating Co-Translational Protein Folding?
ZOOLOGICAL RESEARCH Does mRNA structure contain genetic information for regulating co-translational protein folding? Jian-Rong Yang* Department of Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China ABSTRACT evidenced by unequal usage of synonymous codons and its correlation with efficiency and/or accuracy of translational Currently many facets of genetic information are ill- elongation (Gingold & Pilpel, 2011), mRNA molecule obviously defined. In particular, how protein folding is contains more information than primary protein sequence. This genetically regulated has been a long-standing issue logic and decades of genomic sequencing have elucidated the for genetics and protein biology. And a generic association between codon usage bias and protein structures mechanistic model with supports of genomic data is (Spencer & Barral, 2012; Tsai et al., 2008). still lacking. Recent technological advances have Nevertheless, secondary structure of mRNA is often enabled much needed genome-wide experiments. overlooked, probably due to a lack of scalable experiments for While putting the effect of codon optimality on detecting RNA structure (Eddy, 2014) and the complexity of in debate, these studies have supplied mounting silico prediction for the structure of ribosome-bound mRNA. evidence suggesting a role of mRNA structure in the Recently, this viewpoint has altered due to the latest technical regulation of protein folding by modulating innovations, especially ribosome profiling (Ingolia et al., 2009) translational elongation rate. In conjunctions with and several high-throughput assays for mRNA secondary previous theories, this mechanistic model of protein structure (Graveley, 2016). As a result, a novel regulatory role of folding guided by mRNA structure shall expand our mRNA structure on protein folding emerges.