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The evolution and functional significance of nested gene structures in Drosophila melanogaster.

Lee YC, Chang HH - Genome Biol Evol (2013)

Bottom Line: Interestingly, significantly fewer nested genes are transcribed from the same strand as the including gene.We found that same-strand nested genes are more likely to be single-exon genes.These results support our hypothesis that selection against potential erroneous mRNA splicing when nested and including genes are on the same strand plays an important role in the evolution of nested gene structures.

View Article: PubMed Central - PubMed

Affiliation: Center for Population Biology and Department of Evolution and Ecology, University of California.

ABSTRACT
Nearly 10% of the genes in the genome of Drosophila melanogaster are in nested structures, in which one gene is completely nested within the intron of another gene (nested and including gene, respectively). Even though the coding sequences and untranslated regions of these nested/including gene pairs do not overlap, their intimate structures and the possibility of shared regulatory sequences raise questions about the evolutionary forces governing the origination and subsequent functional and evolutionary impacts of these structures. In this study, we show that nested genes experience weaker evolutionary constraint, have faster rates of protein evolution, and are expressed in fewer tissues than other genes, while including genes show the opposite patterns. Surprisingly, despite completely overlapping with each other, nested and including genes are less likely to display correlated gene expression and biological function than the nearby yet nonoverlapping genes. Interestingly, significantly fewer nested genes are transcribed from the same strand as the including gene. We found that same-strand nested genes are more likely to be single-exon genes. In addition, same-strand including genes are less likely to have known lethal or sterile phenotypes than opposite-strand including genes only when the corresponding nested genes have introns. These results support our hypothesis that selection against potential erroneous mRNA splicing when nested and including genes are on the same strand plays an important role in the evolution of nested gene structures.

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Distributions of Spearman ρ in gene expression for nested/including gene pairs and control gene pairs. Nested/including gene pairs are less positively correlated in their expression level across 20 tissues than control gene pairs, but have similar correlations in expression with nonadjacent pairs of genes on the same chromosome (“random control gene pairs”).
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evt149-F1: Distributions of Spearman ρ in gene expression for nested/including gene pairs and control gene pairs. Nested/including gene pairs are less positively correlated in their expression level across 20 tissues than control gene pairs, but have similar correlations in expression with nonadjacent pairs of genes on the same chromosome (“random control gene pairs”).

Mentions: Nested/including gene pairs are significantly positively correlated (estimated using Spearman rank ρ) in gene expression levels across tissues (FlyAtlas, Chintapalli et al. 2007, MWU, P = 0.025). This is also observed for control gene pairs (MWU, P < 2 × 10−16]. However, the correlations in expression of nested/including gene pairs are significantly weaker (Spearman rank ρ median 0.019 [nested/including gene pairs] vs. 0.174 [control gene pairs], MWU, P = 8.6 × 10−14, fig. 1) and less likely to be positive (52.74% [nested/including gene pairs] vs. 69.44% [control gene pairs]; Fisher’s exact test [FET], P = 4 × 10−9) than control gene pairs. In fact, the correlations in expression of nested/including gene pairs are not different from two randomly chosen genes that are not adjacent but on the same chromosome (“random control gene pairs”; Spearman rank ρ median 0.019 [nested/including gene pairs] vs. 0.032 [random control gene pairs]; MWU, P = 0.76, fig. 1). Furthermore, we employed logistic regression and found that nested/including gene pairs are less likely than control gene pairs to have one gene (nested gene of nested/including gene pairs) to be expressed in the subset of tissues of another gene (including gene of nested/including gene pairs; P = 0.05; odds ratio = 0.78), to have the same highest expressed tissues (P = 8 × 10−11; odds ratio = 0.25), and to be associated with the same GO (Gene Ontology) categories (P = 0.002, 0.001, 0.02; odds ratios = 0.14, 0.17, 0.16 for biological process, molecular function, and cellular component, respectively). Yet, again, when we compared nested/including gene pairs with random control gene pairs, none of these three differences were significant. The correlations in expressional patterns and involvement in biological functions of nested/including genes pairs are significantly different from what have been observed for nearby nonoverlapping genes, suggesting that selection against transcriptional interference might have led to their expression in different tissues and involvement in different biological functions.Fig. 1.—


The evolution and functional significance of nested gene structures in Drosophila melanogaster.

Lee YC, Chang HH - Genome Biol Evol (2013)

Distributions of Spearman ρ in gene expression for nested/including gene pairs and control gene pairs. Nested/including gene pairs are less positively correlated in their expression level across 20 tissues than control gene pairs, but have similar correlations in expression with nonadjacent pairs of genes on the same chromosome (“random control gene pairs”).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814207&req=5

evt149-F1: Distributions of Spearman ρ in gene expression for nested/including gene pairs and control gene pairs. Nested/including gene pairs are less positively correlated in their expression level across 20 tissues than control gene pairs, but have similar correlations in expression with nonadjacent pairs of genes on the same chromosome (“random control gene pairs”).
Mentions: Nested/including gene pairs are significantly positively correlated (estimated using Spearman rank ρ) in gene expression levels across tissues (FlyAtlas, Chintapalli et al. 2007, MWU, P = 0.025). This is also observed for control gene pairs (MWU, P < 2 × 10−16]. However, the correlations in expression of nested/including gene pairs are significantly weaker (Spearman rank ρ median 0.019 [nested/including gene pairs] vs. 0.174 [control gene pairs], MWU, P = 8.6 × 10−14, fig. 1) and less likely to be positive (52.74% [nested/including gene pairs] vs. 69.44% [control gene pairs]; Fisher’s exact test [FET], P = 4 × 10−9) than control gene pairs. In fact, the correlations in expression of nested/including gene pairs are not different from two randomly chosen genes that are not adjacent but on the same chromosome (“random control gene pairs”; Spearman rank ρ median 0.019 [nested/including gene pairs] vs. 0.032 [random control gene pairs]; MWU, P = 0.76, fig. 1). Furthermore, we employed logistic regression and found that nested/including gene pairs are less likely than control gene pairs to have one gene (nested gene of nested/including gene pairs) to be expressed in the subset of tissues of another gene (including gene of nested/including gene pairs; P = 0.05; odds ratio = 0.78), to have the same highest expressed tissues (P = 8 × 10−11; odds ratio = 0.25), and to be associated with the same GO (Gene Ontology) categories (P = 0.002, 0.001, 0.02; odds ratios = 0.14, 0.17, 0.16 for biological process, molecular function, and cellular component, respectively). Yet, again, when we compared nested/including gene pairs with random control gene pairs, none of these three differences were significant. The correlations in expressional patterns and involvement in biological functions of nested/including genes pairs are significantly different from what have been observed for nearby nonoverlapping genes, suggesting that selection against transcriptional interference might have led to their expression in different tissues and involvement in different biological functions.Fig. 1.—

Bottom Line: Interestingly, significantly fewer nested genes are transcribed from the same strand as the including gene.We found that same-strand nested genes are more likely to be single-exon genes.These results support our hypothesis that selection against potential erroneous mRNA splicing when nested and including genes are on the same strand plays an important role in the evolution of nested gene structures.

View Article: PubMed Central - PubMed

Affiliation: Center for Population Biology and Department of Evolution and Ecology, University of California.

ABSTRACT
Nearly 10% of the genes in the genome of Drosophila melanogaster are in nested structures, in which one gene is completely nested within the intron of another gene (nested and including gene, respectively). Even though the coding sequences and untranslated regions of these nested/including gene pairs do not overlap, their intimate structures and the possibility of shared regulatory sequences raise questions about the evolutionary forces governing the origination and subsequent functional and evolutionary impacts of these structures. In this study, we show that nested genes experience weaker evolutionary constraint, have faster rates of protein evolution, and are expressed in fewer tissues than other genes, while including genes show the opposite patterns. Surprisingly, despite completely overlapping with each other, nested and including genes are less likely to display correlated gene expression and biological function than the nearby yet nonoverlapping genes. Interestingly, significantly fewer nested genes are transcribed from the same strand as the including gene. We found that same-strand nested genes are more likely to be single-exon genes. In addition, same-strand including genes are less likely to have known lethal or sterile phenotypes than opposite-strand including genes only when the corresponding nested genes have introns. These results support our hypothesis that selection against potential erroneous mRNA splicing when nested and including genes are on the same strand plays an important role in the evolution of nested gene structures.

Show MeSH
Related in: MedlinePlus