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Divergence of exonic splicing elements after gene duplication and the impact on gene structures.

Zhang Z, Zhou L, Wang P, Liu Y, Chen X, Hu L, Kong X - Genome Biol. (2009)

Bottom Line: When compared to pre-duplication ancestors, we found that there is a significant overall loss of exonic splicing enhancers and the magnitude increases with duplication age.Furthermore, we found that exonic splicing enhancer and silencer changes are mainly caused by synonymous mutations, though nonsynonymous changes also contribute.Finally, we found that exonic splicing enhancer and silencer divergence results in exon splicing state transitions (from constitutive to alternative or vice versa), and that the proportion of paralogous exon pairs with different splicing states also increases over time, consistent with previous predictions.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chong Qing Road, Shanghai 200025, PR China. zhangzg@sibs.ac.cn

ABSTRACT

Background: The origin of new genes and their contribution to functional novelty has been the subject of considerable interest. There has been much progress in understanding the mechanisms by which new genes originate. Here we examine a novel way that new gene structures could originate, namely through the evolution of new alternative splicing isoforms after gene duplication.

Results: We studied the divergence of exonic splicing enhancers and silencers after gene duplication and the contributions of such divergence to the generation of new splicing isoforms. We found that exonic splicing enhancers and exonic splicing silencers diverge especially fast shortly after gene duplication. About 10% and 5% of paralogous exons undergo significantly asymmetric evolution of exonic splicing enhancers and silencers, respectively. When compared to pre-duplication ancestors, we found that there is a significant overall loss of exonic splicing enhancers and the magnitude increases with duplication age. Detailed examination reveals net gains and losses of exonic splicing enhancers and silencers in different copies and paralog clusters after gene duplication. Furthermore, we found that exonic splicing enhancer and silencer changes are mainly caused by synonymous mutations, though nonsynonymous changes also contribute. Finally, we found that exonic splicing enhancer and silencer divergence results in exon splicing state transitions (from constitutive to alternative or vice versa), and that the proportion of paralogous exon pairs with different splicing states also increases over time, consistent with previous predictions.

Conclusions: Our results suggest that exonic splicing enhancer and silencer changes after gene duplication have important roles in alternative splicing divergence and that these changes contribute to the generation of new gene structures.

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The diverse evolutionary pattern of ESEs and ESSs in asymmetric pairs of paralogous exons. The values of relative difference compared to mouse orthologs are plotted for each pair of paralogous exons. For easy visualization, we plot the copy with lower element density (Low) on the abscissa axis and the other with higher density (High) on the ordinate axis. The mean genomic difference for human-mouse orthologous exons are shown by the blue lines in each plot on both axes. The black diagonal line shows the pattern of symmetric evolution. (a) ESEs; (b) ESSs.
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Figure 3: The diverse evolutionary pattern of ESEs and ESSs in asymmetric pairs of paralogous exons. The values of relative difference compared to mouse orthologs are plotted for each pair of paralogous exons. For easy visualization, we plot the copy with lower element density (Low) on the abscissa axis and the other with higher density (High) on the ordinate axis. The mean genomic difference for human-mouse orthologous exons are shown by the blue lines in each plot on both axes. The black diagonal line shows the pattern of symmetric evolution. (a) ESEs; (b) ESSs.

Mentions: The above analysis is based on all the exons in each group of exons together. To explore further the underlying changes of paralogous exons, we examine the exon pairs showing statistically asymmetric evolution (Table 2). For easy visualization, we plot the member with lower ESE or ESS density in each pair of paralogous exons on the abscissa axis and the other with higher density on the ordinate axis (Figure 3); for easy description, we call the two copies 'Low' and 'High', respectively. As shown in Figure 3a, a significant portion of the exon pairs shows discordant changes, with one copy gaining ESEs and the other losing some, or with one copy changing and the other largely constant. We also found some pairs of exons showing gains or losses in both copies (the points near the black diagonal in Figure 3a), though the changing magnitudes are different. A similar pattern was observed for ESS changes (Figure 3b), but the points are sparse due to the small dataset. These observations display a diverse pattern of ESE and ESS evolution after gene duplication, and may reflect different requirements of functional divergence in different genes.


Divergence of exonic splicing elements after gene duplication and the impact on gene structures.

Zhang Z, Zhou L, Wang P, Liu Y, Chen X, Hu L, Kong X - Genome Biol. (2009)

The diverse evolutionary pattern of ESEs and ESSs in asymmetric pairs of paralogous exons. The values of relative difference compared to mouse orthologs are plotted for each pair of paralogous exons. For easy visualization, we plot the copy with lower element density (Low) on the abscissa axis and the other with higher density (High) on the ordinate axis. The mean genomic difference for human-mouse orthologous exons are shown by the blue lines in each plot on both axes. The black diagonal line shows the pattern of symmetric evolution. (a) ESEs; (b) ESSs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3091315&req=5

Figure 3: The diverse evolutionary pattern of ESEs and ESSs in asymmetric pairs of paralogous exons. The values of relative difference compared to mouse orthologs are plotted for each pair of paralogous exons. For easy visualization, we plot the copy with lower element density (Low) on the abscissa axis and the other with higher density (High) on the ordinate axis. The mean genomic difference for human-mouse orthologous exons are shown by the blue lines in each plot on both axes. The black diagonal line shows the pattern of symmetric evolution. (a) ESEs; (b) ESSs.
Mentions: The above analysis is based on all the exons in each group of exons together. To explore further the underlying changes of paralogous exons, we examine the exon pairs showing statistically asymmetric evolution (Table 2). For easy visualization, we plot the member with lower ESE or ESS density in each pair of paralogous exons on the abscissa axis and the other with higher density on the ordinate axis (Figure 3); for easy description, we call the two copies 'Low' and 'High', respectively. As shown in Figure 3a, a significant portion of the exon pairs shows discordant changes, with one copy gaining ESEs and the other losing some, or with one copy changing and the other largely constant. We also found some pairs of exons showing gains or losses in both copies (the points near the black diagonal in Figure 3a), though the changing magnitudes are different. A similar pattern was observed for ESS changes (Figure 3b), but the points are sparse due to the small dataset. These observations display a diverse pattern of ESE and ESS evolution after gene duplication, and may reflect different requirements of functional divergence in different genes.

Bottom Line: When compared to pre-duplication ancestors, we found that there is a significant overall loss of exonic splicing enhancers and the magnitude increases with duplication age.Furthermore, we found that exonic splicing enhancer and silencer changes are mainly caused by synonymous mutations, though nonsynonymous changes also contribute.Finally, we found that exonic splicing enhancer and silencer divergence results in exon splicing state transitions (from constitutive to alternative or vice versa), and that the proportion of paralogous exon pairs with different splicing states also increases over time, consistent with previous predictions.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chong Qing Road, Shanghai 200025, PR China. zhangzg@sibs.ac.cn

ABSTRACT

Background: The origin of new genes and their contribution to functional novelty has been the subject of considerable interest. There has been much progress in understanding the mechanisms by which new genes originate. Here we examine a novel way that new gene structures could originate, namely through the evolution of new alternative splicing isoforms after gene duplication.

Results: We studied the divergence of exonic splicing enhancers and silencers after gene duplication and the contributions of such divergence to the generation of new splicing isoforms. We found that exonic splicing enhancers and exonic splicing silencers diverge especially fast shortly after gene duplication. About 10% and 5% of paralogous exons undergo significantly asymmetric evolution of exonic splicing enhancers and silencers, respectively. When compared to pre-duplication ancestors, we found that there is a significant overall loss of exonic splicing enhancers and the magnitude increases with duplication age. Detailed examination reveals net gains and losses of exonic splicing enhancers and silencers in different copies and paralog clusters after gene duplication. Furthermore, we found that exonic splicing enhancer and silencer changes are mainly caused by synonymous mutations, though nonsynonymous changes also contribute. Finally, we found that exonic splicing enhancer and silencer divergence results in exon splicing state transitions (from constitutive to alternative or vice versa), and that the proportion of paralogous exon pairs with different splicing states also increases over time, consistent with previous predictions.

Conclusions: Our results suggest that exonic splicing enhancer and silencer changes after gene duplication have important roles in alternative splicing divergence and that these changes contribute to the generation of new gene structures.

Show MeSH