The (In)dependence of alternative splicing and gene duplication

David Talavera, Christine Vogel, Modesto Orozco, Sarah A. Teichmann, Xavier De La Cruz

Research output: Contribution to journalArticle

Abstract

Alternative splicing (AS) and gene duplication (GD) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by AS may be comparable to those introduced by GD. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of AS and GD per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in mRNA expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of AS and GD at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of AS and GD in a gene family, and to the selection pressure imposed by the environment.

Original languageEnglish (US)
Pages (from-to)375-388
Number of pages14
JournalPLoS Computational Biology
Volume3
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Alternative Splicing
Gene Duplication
alternative splicing
gene duplication
Duplication
Genes
Gene
gene
Proteins
protein structure
protein
genes
amino acid sequences
Duplicate Genes
genomics
duplicate genes
proteins
Protein Structure
Protein Sequence
Insertional Mutagenesis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

The (In)dependence of alternative splicing and gene duplication. / Talavera, David; Vogel, Christine; Orozco, Modesto; Teichmann, Sarah A.; De La Cruz, Xavier.

In: PLoS Computational Biology, Vol. 3, No. 3, 03.2007, p. 375-388.

Research output: Contribution to journalArticle

Talavera, David ; Vogel, Christine ; Orozco, Modesto ; Teichmann, Sarah A. ; De La Cruz, Xavier. / The (In)dependence of alternative splicing and gene duplication. In: PLoS Computational Biology. 2007 ; Vol. 3, No. 3. pp. 375-388.
@article{82f5bf8eecca45e994ddb18bb77b6d64,
title = "The (In)dependence of alternative splicing and gene duplication",
abstract = "Alternative splicing (AS) and gene duplication (GD) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by AS may be comparable to those introduced by GD. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of AS and GD per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in mRNA expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of AS and GD at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of AS and GD in a gene family, and to the selection pressure imposed by the environment.",
author = "David Talavera and Christine Vogel and Modesto Orozco and Teichmann, {Sarah A.} and {De La Cruz}, Xavier",
year = "2007",
month = "3",
doi = "10.1371/journal.pcbi.0030033",
language = "English (US)",
volume = "3",
pages = "375--388",
journal = "PLoS Computational Biology",
issn = "1553-734X",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - The (In)dependence of alternative splicing and gene duplication

AU - Talavera, David

AU - Vogel, Christine

AU - Orozco, Modesto

AU - Teichmann, Sarah A.

AU - De La Cruz, Xavier

PY - 2007/3

Y1 - 2007/3

N2 - Alternative splicing (AS) and gene duplication (GD) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by AS may be comparable to those introduced by GD. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of AS and GD per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in mRNA expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of AS and GD at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of AS and GD in a gene family, and to the selection pressure imposed by the environment.

AB - Alternative splicing (AS) and gene duplication (GD) both are processes that diversify the protein repertoire. Recent examples have shown that sequence changes introduced by AS may be comparable to those introduced by GD. In addition, the two processes are inversely correlated at the genomic scale: large gene families are depleted in splice variants and vice versa. All together, these data strongly suggest that both phenomena result in interchangeability between their effects. Here, we tested the extent to which this applies with respect to various protein characteristics. The amounts of AS and GD per gene are anticorrelated even when accounting for different gene functions or degrees of sequence divergence. In contrast, the two processes appear to be independent in their influence on variation in mRNA expression. Further, we conducted a detailed comparison of the effect of sequence changes in both alternative splice variants and gene duplicates on protein structure, in particular the size, location, and types of sequence substitutions and insertions/deletions. We find that, in general, alternative splicing affects protein sequence and structure in a more drastic way than gene duplication and subsequent divergence. Our results reveal an interesting paradox between the anticorrelation of AS and GD at the genomic level, and their impact at the protein level, which shows little or no equivalence in terms of effects on protein sequence, structure, and function. We discuss possible explanations that relate to the order of appearance of AS and GD in a gene family, and to the selection pressure imposed by the environment.

UR - http://www.scopus.com/inward/record.url?scp=34047232679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047232679&partnerID=8YFLogxK

U2 - 10.1371/journal.pcbi.0030033

DO - 10.1371/journal.pcbi.0030033

M3 - Article

VL - 3

SP - 375

EP - 388

JO - PLoS Computational Biology

JF - PLoS Computational Biology

SN - 1553-734X

IS - 3

ER -