Skip Navigation


MBE Advance Access originally published online on October 12, 2005
Molecular Biology and Evolution 2006 23(2):301-309; doi:10.1093/molbev/msj035
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
23/2/301    most recent
msj035v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (38)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Parmley, J. L.
Right arrow Articles by Hurst, L. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Parmley, J. L.
Right arrow Articles by Hurst, L. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Evidence for Purifying Selection Against Synonymous Mutations in Mammalian Exonic Splicing Enhancers

Joanna L. Parmley, J. V. Chamary and Laurence D. Hurst

Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom

E-mail: l.d.hurst{at}bath.ac.uk.

Silent sites in mammals have classically been assumed to be free from selective pressures. Consequently, the synonymous substitution rate (Ks) is often used as a proxy for the mutation rate. Although accumulating evidence demonstrates that the assumption is not valid, the mechanism by which selection acts remain unclear. Recent work has revealed that the presence of exonic splicing enhancers (ESEs) in coding sequence might influence synonymous evolution. ESEs are predominantly located near intron-exon junctions, which may explain the reduced single-nucleotide polymorphism (SNP) density in these regions. Here we show that synonymous sites in putative ESEs evolve more slowly than the remaining exonic sequence. Differential mutabilities of ESEs do not appear to explain this difference. We observe that substitution frequency at fourfold synonymous sites decreases as one approaches the ends of exons, consistent with the existing SNP data. This gradient is at least in part explained by ESEs being more abundant near junctions. Between-gene variation in Ks is hence partly explained by the proportion of the gene that acts as an ESE. Given the relative abundance of ESEs and the reduced rates of synonymous divergence within them, we estimate that constraints on synonymous evolution within ESEs causes the true mutation rate to be underestimated by not more than ~8%. We also find that Ks outside of ESEs is much lower in alternatively spliced exons than in constitutive exons, implying that other causes of selection on synonymous mutations exist. Additionally, selection on ESEs appears to affect nonsynonymous sites and may explain why amino acid usage near intron-exon junctions is nonrandom.

Key Words: codon usage bias • mutation rate • purifying selection • splicing • synonymous sites


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Genome ResHome page
S. Ke, X. H.-F. Zhang, and L. A. Chasin
Positive selection acting on splicing motifs reflects compensatory evolution
Genome Res., April 1, 2008; 18(4): 533 - 543.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. Subramanian
Nearly Neutrality and the Evolution of Codon Usage Bias in Eukaryotic Genomes
Genetics, April 1, 2008; 178(4): 2429 - 2432.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
A. Goren, E. Kim, M. Amit, R. Bochner, G. Lev-Maor, N. Ahituv, and G. Ast
Alternative approach to a heavy weight problem
Genome Res., February 1, 2008; 18(2): 214 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
G. H. Perry, R. D. Martin, and B. C. Verrelli
Signatures of Functional Constraint at Aye-aye Opsin Genes: The Potential of Adaptive Color Vision in a Nocturnal Primate
Mol. Biol. Evol., September 1, 2007; 24(9): 1963 - 1970.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
A. M. Resch, L. Carmel, L. Marino-Ramirez, A. Y. Ogurtsov, S. A. Shabalina, I. B. Rogozin, and E. V. Koonin
Widespread Positive Selection in Synonymous Sites of Mammalian Genes
Mol. Biol. Evol., August 1, 2007; 24(8): 1821 - 1831.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
J. L. Parmley and L. D. Hurst
Exonic Splicing Regulatory Elements Skew Synonymous Codon Usage near Intron-exon Boundaries in Mammals
Mol. Biol. Evol., August 1, 2007; 24(8): 1600 - 1603.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
E. Buratti, A. Dhir, M. A. Lewandowska, and F. E. Baralle
RNA structure is a key regulatory element in pathological ATM and CFTR pseudoexon inclusion events
Nucleic Acids Res., July 26, 2007; 35(13): 4369 - 4383.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. Raponi, F. E. Baralle, and F. Pagani
Reduced splicing efficiency induced by synonymous substitutions may generate a substrate for natural selection of new splicing isoforms: the case of CFTR exon 12
Nucleic Acids Res., January 28, 2007; 35(2): 606 - 613.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
A. D. Cutter, J. D. Wasmuth, and M. L. Blaxter
The Evolution of Biased Codon and Amino Acid Usage in Nematode Genomes
Mol. Biol. Evol., December 1, 2006; 23(12): 2303 - 2315.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. Subramanian and S. Kumar
Higher Intensity of Purifying Selection on >90% of the Human Genes Revealed by the Intrinsic Replacement Mutation Rates
Mol. Biol. Evol., December 1, 2006; 23(12): 2283 - 2287.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
X. H.-F. Zhang and L. A. Chasin
Comparison of multiple vertebrate genomes reveals the birth and evolution of human exons
PNAS, September 5, 2006; 103(36): 13427 - 13432.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
P. Schattner and M. Diekhans
Regions of extreme synonymous codon selection in mammalian genes
Nucleic Acids Res., March 23, 2006; 34(6): 1700 - 1710.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.