Exonic splice regulation imposes strong selection at synonymous sites.

Genome Research
Rosina Savisaar, Laurence D Hurst

Abstract

What proportion of coding sequence nucleotides have roles in splicing, and how strong is the selection that maintains them? Despite a large body of research into exonic splice regulatory signals, these questions have not been answered. This is because, to our knowledge, previous investigations have not explicitly disentangled the frequency of splice regulatory elements from the strength of the evolutionary constraint under which they evolve. Current data are consistent both with a scenario of weak and diffuse constraint, enveloping large swaths of sequence, as well as with well-defined pockets of strong purifying selection. In the former case, natural selection on exonic splice enhancers (ESEs) might primarily act as a slight modifier of codon usage bias. In the latter, mutations that disrupt ESEs are likely to have large fitness and, potentially, clinical effects. To distinguish between these scenarios, we used several different methods to determine the distribution of selection coefficients for new mutations within ESEs. The analyses converged to suggest that ∼15%-20% of fourfold degenerate sites are part of functional ESEs. Most of these sites are under strong evolutionary constraint. Therefore, exonic splice regulation does...Continue Reading

References

Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J Sved, A Bird
Mar 1, 1993·Genes & Development·A WatakabeY Shimura
Oct 29, 1997·Journal of Molecular Evolution·E N Moriyama, J R Powell
Jul 13, 2002·Science·William G FairbrotherChristopher B Burge
Aug 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gwenaël Piganeau, Adam Eyre-Walker
Dec 9, 2003·Molecular Biology and Evolution·Adam Siepel, David Haussler
Apr 15, 2004·Genes & Development·Jeremy R SanfordJavier F Cáceres
May 18, 2004·Genes & Development·Xiang H-F Zhang, Lawrence A Chasin
Aug 25, 2004·Biochemical and Biophysical Research Communications·Uberto PozzoliManuela Sironi
Sep 2, 2004·PLoS Biology·William G FairbrotherPhillip A Sharp
Sep 28, 2004·Nucleic Acids Research·Mario dos ReisLorenz Wernisch
Dec 21, 2004·Cell·Zefeng WangChristopher B Burge
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jian Lu, Chung-I Wu
May 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Scott H WilliamsonCarlos D Bustamante
Sep 22, 2005·Human Molecular Genetics·Lev Y YampolskyAlexey S Kondrashov
Oct 14, 2005·Molecular Biology and Evolution·Joanna L ParmleyLaurence D Hurst
Nov 22, 2005·Genetics·Laurence LoeweVéronique Nöel
Dec 2, 2005·Journal of Molecular Evolution·David B Carlini, Jordan E Genut
Dec 14, 2005·Journal of Theoretical Biology·Fyodor A KondrashovAlexey S Kondrashov
Apr 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Josep M Comeron
Feb 15, 2007·PLoS Biology·Joanna L ParmleyLaurence D Hurst
May 25, 2007·Molecular Biology and Evolution·Alissa M ReschEugene V Koonin
May 26, 2007·Molecular Biology and Evolution·Joanna L Parmley, Laurence D Hurst
Jul 20, 2007·Nature Reviews. Genetics·Adam Eyre-Walker, Peter D Keightley
Aug 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ichiro TaniguchiMutsuhito Ohno
Jan 22, 2008·Genome Research·Shengdong KeLawrence A Chasin
Jun 3, 2008·PLoS Genetics·Adam R BoykoCarlos D Bustamante
Sep 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Joshua J FormanHilary A Coller
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall

❮ Previous
Next ❯

Citations

Dec 17, 2019·Molecular Biology and Evolution·Liam Abrahams, Laurence D Hurst
Feb 12, 2020·Nature Plants·Zoé Joly-LopezMichael D Purugganan
Jun 7, 2020·Nature Communications·Stephen RongWilliam G Fairbrother
Apr 10, 2019·Genome Research·Nicolas FontrodonaDidier Auboeuf
Jun 14, 2019·Nature Communications·Yogita SharmaSven Diederichs
Mar 3, 2020·Genome Biology and Evolution·Kai HayesKai Zeng
May 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Shakibur RahmanJody Hey
Jun 23, 2021·Wiley Interdisciplinary Reviews. RNA·Eleanor R Gaunt, Paul Digard

❮ 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.