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Complexity of gene expression evolution after duplication: protein dosage rebalancing.

Rogozin IB - Genet Res Int (2014)

Bottom Line: Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy.The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model.This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

ABSTRACT
Ongoing debates about functional importance of gene duplications have been recently intensified by a heated discussion of the "ortholog conjecture" (OC). Under the OC, which is central to functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of gene ontology (GO) annotations and expression profiles, among within-species paralogs compared to orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model. This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes.

No MeSH data available.


Expression and sequence similarity of orthologous and paralogous genes. (a) Z-score expression similarity averaged across 4 tissues. (b) Rank-based expression similarity averaged across 4 tissues. (c) Kendall's τ rank correlation coefficient. (d) Pearson linear correlation coefficient. The raw data is taken from Rogozin and coworkers [34]; see Table 1 for more details about procedures used in this study.
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fig1: Expression and sequence similarity of orthologous and paralogous genes. (a) Z-score expression similarity averaged across 4 tissues. (b) Rank-based expression similarity averaged across 4 tissues. (c) Kendall's τ rank correlation coefficient. (d) Pearson linear correlation coefficient. The raw data is taken from Rogozin and coworkers [34]; see Table 1 for more details about procedures used in this study.

Mentions: Rogozin and coworkers reanalyzed these controversial results using approaches different as much as possible from those used before and reconciled them with the literature on gene duplications [34]. This analysis of a large RNA-Seq dataset of multiple tissues from human and mouse shows that rank/Z-score measures of the expression similarity between orthologs are significantly higher than that between within-species paralogs (Figures 1(a) and 1(b)), supporting the OC. This result is consistent with Chen and Zhang study [32]. The plots of expression similarity measured using linear or rank correlation coefficients were qualitatively similar to the analogous plots reported by Nehrt and colleagues [26] (Figures 1(c) and 1(d)) in that the strongest correlation was observed among within-species paralogs, followed by orthologs and then by between-species paralogs. For the between-species paralogs, significant expression similarity was observed only at low sequence divergence whereas at higher divergence, the correlation coefficient values were much lower (Figures 1(c) and 1(d)). Although the correlation among within-species paralogs was high for all values of sequence divergence, it also dropped with increasing divergence (Figures 1(c) and 1(d)). It was suggested that different measures of expression similarity could reflect different salient features of gene expression, namely, tissue-specificity in the case of the correlation coefficients and relative abundance of individual mRNAs in the case of Z-scores and ranking scores [34]. Further analysis in which expression profiles of orthologs and paralogs were compared separately for individual gene families provided a strong argument in support of the OC [34]. However, the OC, all its importance notwithstanding, reflects only one aspect of gene evolution. The complete picture must integrate vertical descent encapsulated in the OC with the lineage-specific aspects of the evolution of paralogs; it should be interpreted also in the context of various hypotheses on evolution of gene duplications [34].


Complexity of gene expression evolution after duplication: protein dosage rebalancing.

Rogozin IB - Genet Res Int (2014)

Expression and sequence similarity of orthologous and paralogous genes. (a) Z-score expression similarity averaged across 4 tissues. (b) Rank-based expression similarity averaged across 4 tissues. (c) Kendall's τ rank correlation coefficient. (d) Pearson linear correlation coefficient. The raw data is taken from Rogozin and coworkers [34]; see Table 1 for more details about procedures used in this study.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4150538&req=5

fig1: Expression and sequence similarity of orthologous and paralogous genes. (a) Z-score expression similarity averaged across 4 tissues. (b) Rank-based expression similarity averaged across 4 tissues. (c) Kendall's τ rank correlation coefficient. (d) Pearson linear correlation coefficient. The raw data is taken from Rogozin and coworkers [34]; see Table 1 for more details about procedures used in this study.
Mentions: Rogozin and coworkers reanalyzed these controversial results using approaches different as much as possible from those used before and reconciled them with the literature on gene duplications [34]. This analysis of a large RNA-Seq dataset of multiple tissues from human and mouse shows that rank/Z-score measures of the expression similarity between orthologs are significantly higher than that between within-species paralogs (Figures 1(a) and 1(b)), supporting the OC. This result is consistent with Chen and Zhang study [32]. The plots of expression similarity measured using linear or rank correlation coefficients were qualitatively similar to the analogous plots reported by Nehrt and colleagues [26] (Figures 1(c) and 1(d)) in that the strongest correlation was observed among within-species paralogs, followed by orthologs and then by between-species paralogs. For the between-species paralogs, significant expression similarity was observed only at low sequence divergence whereas at higher divergence, the correlation coefficient values were much lower (Figures 1(c) and 1(d)). Although the correlation among within-species paralogs was high for all values of sequence divergence, it also dropped with increasing divergence (Figures 1(c) and 1(d)). It was suggested that different measures of expression similarity could reflect different salient features of gene expression, namely, tissue-specificity in the case of the correlation coefficients and relative abundance of individual mRNAs in the case of Z-scores and ranking scores [34]. Further analysis in which expression profiles of orthologs and paralogs were compared separately for individual gene families provided a strong argument in support of the OC [34]. However, the OC, all its importance notwithstanding, reflects only one aspect of gene evolution. The complete picture must integrate vertical descent encapsulated in the OC with the lineage-specific aspects of the evolution of paralogs; it should be interpreted also in the context of various hypotheses on evolution of gene duplications [34].

Bottom Line: Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy.The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model.This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes.

View Article: PubMed Central - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

ABSTRACT
Ongoing debates about functional importance of gene duplications have been recently intensified by a heated discussion of the "ortholog conjecture" (OC). Under the OC, which is central to functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of gene ontology (GO) annotations and expression profiles, among within-species paralogs compared to orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model. This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes.

No MeSH data available.