Positive selection acting on splicing motifs reflects compensatory evolution.

Genome Research
Shengdong KeLawrence A Chasin

Abstract

We have used comparative genomics to characterize the evolutionary behavior of predicted splicing regulatory motifs. Using base substitution rates in intronic regions as a calibrator for neutral change, we found a strong avoidance of synonymous substitutions that disrupt predicted exonic splicing enhancers or create predicted exonic splicing silencers. These results attest to the functionality of the hexameric motif set used and suggest that they are subject to purifying selection. We also found that synonymous substitutions in constitutive exons tend to create exonic splicing enhancers and to disrupt exonic splicing silencers, implying positive selection for these splicing promoting events. We present evidence that this positive selection is the result of splicing-positive events compensating for splicing-negative events as well as for mutations that weaken splice-site sequences. Such compensatory events include nonsynonymous mutations, synonymous mutations, and mutations at splice sites. Compensation was also seen from the fact that orthologous exons tend to maintain the same number of predicted splicing motifs. Our data fit a splicing compensation model of exon evolution, in which selection for splicing-positive mutations ta...Continue Reading

References

Jun 20, 1991·Nature·J H McDonald, M Kreitman
Jan 5, 1990·Journal of Molecular Biology·A L LearI C Eperon
Sep 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·C W Birky, J B Walsh
Aug 1, 1993·Genetics·B CharlesworthD Charlesworth
May 29, 2000·BMJ : British Medical Journal·J M Bland, D G Altman
Aug 11, 2000·Molecular and Cellular Biology·H Sun, L A Chasin
Jul 13, 2002·Science·William G FairbrotherChristopher B Burge
Aug 15, 2002·Trends in Genetics : TIG·Laurence D Hurst
May 3, 2003·Genome Research·Ines HellmannSvante Paabo
Aug 26, 2003·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Peter F ArndtTerence Hwa
Nov 14, 2003·Genome Research·Elizabeth LouieJacek Majewski
Dec 9, 2003·Molecular Biology and Evolution·Adam Siepel, David Haussler
May 18, 2004·Genes & Development·Xiang H-F Zhang, Lawrence A Chasin
Aug 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Dick G Hwang, Phil Green
Sep 2, 2004·PLoS Biology·William G FairbrotherPhillip A Sharp
Oct 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Gene YeoChristopher B Burge
Dec 21, 2004·Cell·Zefeng WangChristopher B Burge
Jan 22, 2005·Trends in Genetics : TIG·Qun PanBenjamin J Blencowe
Feb 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gene W YeoChristopher B Burge
Jun 3, 2005·Genome Research·Xiang H-F ZhangLawrence A Chasin
Aug 2, 2005·Molecular and Cellular Biology·Xiang H-F ZhangLawrence A Chasin
Aug 27, 2005·Molecular Biology and Evolution·Josep M Comeron, Theodore B Guthrie
Sep 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yi Xing, Christopher Lee
Oct 14, 2005·Molecular Biology and Evolution·Joanna L ParmleyLaurence D Hurst
Nov 30, 2005·Methods : a Companion to Methods in Enzymology·Xiang H-F ZhangLawrence A Chasin
Dec 2, 2005·Journal of Molecular Evolution·David B Carlini, Jordan E Genut
Dec 22, 2005·Molecular Biology and Evolution·Feng-Chi ChenTrees-Juen Chuang
Jan 19, 2006·Nature Reviews. Genetics·J V ChamaryLaurence D Hurst
Feb 21, 2006·Gene·Yi Xing, Christopher Lee
Jun 27, 2006·Molecular Cell·Zefeng WangChristopher B Burge
Nov 24, 2006·PLoS Genetics·Michael B StadlerChristopher B Burge
May 25, 2007·Molecular Biology and Evolution·Alissa M ReschEugene V Koonin
Jun 9, 2007·Genome Research·Kavita Garg, Phil Green

❮ Previous
Next ❯

Citations

Sep 18, 2012·Nature Structural & Molecular Biology·Yang WangZefeng Wang
Apr 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Chaolin ZhangMichael Q Zhang
May 13, 2010·Human Molecular Genetics·Lan LinYi Xing
Aug 30, 2011·Molecular Biology and Evolution·Sudhir KumarKoichiro Tamura
Jan 8, 2013·Pharmacogenetics and Genomics·A Joseph BloomAlison Goate
Sep 12, 2009·Genome Research·Manuel IrimiaEugene V Koonin
Apr 18, 2012·Biology Direct·Igor B RogozinEugene V Koonin
Sep 25, 2008·Genome Biology·André Corvelo, Eduardo Eyras
Nov 26, 2009·Genome Biology·Deniz KuralJeffrey H Chuang
Feb 18, 2010·Genome Biology·Adam WoolfeLaura Elnitski
Aug 14, 2010·Genome Biology·Shengdong Ke, Lawrence A Chasin
Sep 12, 2012·Genetics·Hiroshi AkashiTomoko Ohta
Mar 27, 2013·Journal of Molecular Evolution·Rodrigo F RamalhoDiogo Meyer
Apr 3, 2014·Nucleic Acids Research·Alessia FalangaMarco Baralle
Aug 26, 2014·Nucleic Acids Research·Steffen ErkelenzHeiner Schaal
Jan 21, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Manuel IrimiaJordi Garcia-Fernandez
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Xinshu Xiao, Jae-Hyung Lee
Apr 29, 2015·Breast Cancer Research and Treatment·Ji WenXiaodong Cai
Mar 20, 2009·Genome Biology·Martin AkermanYael Mandel-Gutfreund
Aug 26, 2018·Genome Research·Rosina Savisaar, Laurence D Hurst
Apr 9, 2010·Nature Reviews. Genetics·Hadas KerenGil Ast
Dec 16, 2017·Genome Research·Shengdong KeLawrence A Chasin
Apr 15, 2020·NPJ Genomic Medicine·Daniele MericoBrendan J Frey
Oct 2, 2015·The Journal of Biological Chemistry·William F MuellerKlemens J Hertel
Jan 1, 2017·Nucleic Acids Research·Anna-Lena BrillenHeiner Schaal
Apr 19, 2017·Nature Genetics·Rachel SoemediWilliam G Fairbrother
Feb 14, 2021·NPJ Genomic Medicine·Daniele MericoBrendan J Frey
Jul 12, 2014·Biology Direct·Eugenia PoliakovIgor B Rogozin
Jun 11, 2011·Genome Research·Shengdong KeLawrence A Chasin
Dec 11, 2014·RNA·Mauricio A AriasLawrence A Chasin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.