Detecting Functional Divergence after Gene Duplication through Evolutionary Changes in Posttranslational Regulatory Sequences

Alex N. Nguyen Ba, Bob Strome, Jun Jie Hua, Jonathan Desmond, Isabelle Gagnon-Arsenault, Eric L Weiss, Christian R. Landry, Alan M. Moses

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Gene duplication is an important evolutionary mechanism that can result in functional divergence in paralogs due to neo-functionalization or sub-functionalization. Consistent with functional divergence after gene duplication, recent studies have shown accelerated evolution in retained paralogs. However, little is known in general about the impact of this accelerated evolution on the molecular functions of retained paralogs. For example, do new functions typically involve changes in enzymatic activities, or changes in protein regulation? Here we study the evolution of posttranslational regulation by examining the evolution of important regulatory sequences (short linear motifs) in retained duplicates created by the whole-genome duplication in budding yeast. To do so, we identified short linear motifs whose evolutionary constraint has relaxed after gene duplication with a likelihood-ratio test that can account for heterogeneity in the evolutionary process by using a non-central chi-squared null distribution. We find that short linear motifs are more likely to show changes in evolutionary constraints in retained duplicates compared to single-copy genes. We examine changes in constraints on known regulatory sequences and show that for the Rck1/Rck2, Fkh1/Fkh2, Ace2/Swi5 paralogs, they are associated with previously characterized differences in posttranslational regulation. Finally, we experimentally confirm our prediction that for the Ace2/Swi5 paralogs, Cbk1 regulated localization was lost along the lineage leading to SWI5 after gene duplication. Our analysis suggests that changes in posttranslational regulation mediated by short regulatory motifs systematically contribute to functional divergence after gene duplication.

Original languageEnglish (US)
JournalPLoS Computational Biology
Volume10
Issue number12
DOIs
StatePublished - Jan 1 2014

Fingerprint

regulatory sequences
Gene Duplication
gene duplication
Duplication
Divergence
Genes
divergence
Gene
gene
Functionalization
Saccharomycetales
Molecular Evolution
Chi-squared distribution
Null Distribution
Likelihood Ratio Test
Yeast
yeast
Genome
yeasts
genome

ASJC Scopus subject areas

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

Cite this

Nguyen Ba, Alex N. ; Strome, Bob ; Hua, Jun Jie ; Desmond, Jonathan ; Gagnon-Arsenault, Isabelle ; Weiss, Eric L ; Landry, Christian R. ; Moses, Alan M. / Detecting Functional Divergence after Gene Duplication through Evolutionary Changes in Posttranslational Regulatory Sequences. In: PLoS Computational Biology. 2014 ; Vol. 10, No. 12.
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Detecting Functional Divergence after Gene Duplication through Evolutionary Changes in Posttranslational Regulatory Sequences. / Nguyen Ba, Alex N.; Strome, Bob; Hua, Jun Jie; Desmond, Jonathan; Gagnon-Arsenault, Isabelle; Weiss, Eric L; Landry, Christian R.; Moses, Alan M.

In: PLoS Computational Biology, Vol. 10, No. 12, 01.01.2014.

Research output: Contribution to journalArticle

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