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Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.

Lee JY, Ji Z, Tian B - Nucleic Acids Res. (2008)

Bottom Line: We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved.We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized.Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Biomedical Sciences and Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

ABSTRACT
mRNA polyadenylation is an essential step for the maturation of almost all eukaryotic mRNAs, and is tightly coupled with termination of transcription in defining the 3'-end of genes. Large numbers of human and mouse genes harbor alternative polyadenylation sites [poly(A) sites] that lead to mRNA variants containing different 3'-untranslated regions (UTRs) and/or encoding distinct protein sequences. Here, we examined the conservation and divergence of different types of alternative poly(A) sites across human, mouse, rat and chicken. We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved. Genes with longer evolutionary history are more likely to have alternative polyadenylation, suggesting gain of poly(A) sites through evolution. We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized. Different classes of TEs have different characteristics in their association with poly(A) sites via exaptation of TE sequences into polyadenylation elements. Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

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Poly(A) sites and TEs. (A) Percent of human poly(A) sites associated with TEs for different types of conserved and nonconserved sites. Both TEs overlapping with poly(A) site regions in the auxiliary regions (−100 to −41nt and +41 to +100 nt) and core region are shown. (B) Usage of different types of poly(A) sites. Percent of poly(A) site usage is based on the number of supporting ESTs for a poly(A) site compared with the number of ESTs for all poly(A) sites of the same gene. (C) Schematic of three types of association between TE and poly(A) site. The top horizontal line represents a poly(A) site region with the arrow pointing to a poly(A) site. TEs are represented by horizontal bars. Three types of placement of a TE in a poly(A) site region are shown. In type 1, a TE contains a poly(A) site and adjacent upstream and downstream regions; in types 2 and 3, only the upstream or downstream region of a poly(A) site is contained in a TE. The type number is indicated in the graph. (D) Number of poly(A) sites associated with four classes of TEs. The three types of association and TE strand are indicated.
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Figure 3: Poly(A) sites and TEs. (A) Percent of human poly(A) sites associated with TEs for different types of conserved and nonconserved sites. Both TEs overlapping with poly(A) site regions in the auxiliary regions (−100 to −41nt and +41 to +100 nt) and core region are shown. (B) Usage of different types of poly(A) sites. Percent of poly(A) site usage is based on the number of supporting ESTs for a poly(A) site compared with the number of ESTs for all poly(A) sites of the same gene. (C) Schematic of three types of association between TE and poly(A) site. The top horizontal line represents a poly(A) site region with the arrow pointing to a poly(A) site. TEs are represented by horizontal bars. Three types of placement of a TE in a poly(A) site region are shown. In type 1, a TE contains a poly(A) site and adjacent upstream and downstream regions; in types 2 and 3, only the upstream or downstream region of a poly(A) site is contained in a TE. The type number is indicated in the graph. (D) Number of poly(A) sites associated with four classes of TEs. The three types of association and TE strand are indicated.

Mentions: A large number of human poly(A) sites are not conserved in mouse, a sizable fraction of which is due to lack of genome alignments (data not shown). Since TEs have been implicated in giving rise to new exon sequences in evolution, we wanted to know how TEs might be responsible for species-specific poly(A) sites. Using the RepeatMasker program and the RepBase database, we examined poly(A) sites that are associated with four classes of TEs, i.e. DNAs, LINEs, LTRs and SINEs. A TE can contain a poly(A) site or contribute cis-elements to a poly(A) site. For the latter case, we required the distance between a poly(A) site and a TE to be within 40 nt, as essential cis-elements involved in polyadenylation are typically located in the −40 to +40 nt core region (11). In sum, 3188 human poly(A) sites from 2565 genes, corresponding to ∼8% of all poly(A) sites and ∼16% of all genes surveyed, were found to be associated with TEs. As shown in Figure 3A, we found that human poly(A) sites that are not conserved in mouse are associated with TEs to a much greater extent than those conserved ones. In fact, ∼94% of TE-associated sites are nonconserved in mouse. Conversely, ∼5% of mouse poly(A) sites from ∼7% of genes surveyed are associated with TEs, of which ∼93% are not conserved in human (data not shown). This result indicates that TEs can significantly contribute to creation or modulation of poly(A) sites in evolution, and are responsible for species-specific poly(A) sites.Figure 3.


Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3'-end of genes.

Lee JY, Ji Z, Tian B - Nucleic Acids Res. (2008)

Poly(A) sites and TEs. (A) Percent of human poly(A) sites associated with TEs for different types of conserved and nonconserved sites. Both TEs overlapping with poly(A) site regions in the auxiliary regions (−100 to −41nt and +41 to +100 nt) and core region are shown. (B) Usage of different types of poly(A) sites. Percent of poly(A) site usage is based on the number of supporting ESTs for a poly(A) site compared with the number of ESTs for all poly(A) sites of the same gene. (C) Schematic of three types of association between TE and poly(A) site. The top horizontal line represents a poly(A) site region with the arrow pointing to a poly(A) site. TEs are represented by horizontal bars. Three types of placement of a TE in a poly(A) site region are shown. In type 1, a TE contains a poly(A) site and adjacent upstream and downstream regions; in types 2 and 3, only the upstream or downstream region of a poly(A) site is contained in a TE. The type number is indicated in the graph. (D) Number of poly(A) sites associated with four classes of TEs. The three types of association and TE strand are indicated.
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Figure 3: Poly(A) sites and TEs. (A) Percent of human poly(A) sites associated with TEs for different types of conserved and nonconserved sites. Both TEs overlapping with poly(A) site regions in the auxiliary regions (−100 to −41nt and +41 to +100 nt) and core region are shown. (B) Usage of different types of poly(A) sites. Percent of poly(A) site usage is based on the number of supporting ESTs for a poly(A) site compared with the number of ESTs for all poly(A) sites of the same gene. (C) Schematic of three types of association between TE and poly(A) site. The top horizontal line represents a poly(A) site region with the arrow pointing to a poly(A) site. TEs are represented by horizontal bars. Three types of placement of a TE in a poly(A) site region are shown. In type 1, a TE contains a poly(A) site and adjacent upstream and downstream regions; in types 2 and 3, only the upstream or downstream region of a poly(A) site is contained in a TE. The type number is indicated in the graph. (D) Number of poly(A) sites associated with four classes of TEs. The three types of association and TE strand are indicated.
Mentions: A large number of human poly(A) sites are not conserved in mouse, a sizable fraction of which is due to lack of genome alignments (data not shown). Since TEs have been implicated in giving rise to new exon sequences in evolution, we wanted to know how TEs might be responsible for species-specific poly(A) sites. Using the RepeatMasker program and the RepBase database, we examined poly(A) sites that are associated with four classes of TEs, i.e. DNAs, LINEs, LTRs and SINEs. A TE can contain a poly(A) site or contribute cis-elements to a poly(A) site. For the latter case, we required the distance between a poly(A) site and a TE to be within 40 nt, as essential cis-elements involved in polyadenylation are typically located in the −40 to +40 nt core region (11). In sum, 3188 human poly(A) sites from 2565 genes, corresponding to ∼8% of all poly(A) sites and ∼16% of all genes surveyed, were found to be associated with TEs. As shown in Figure 3A, we found that human poly(A) sites that are not conserved in mouse are associated with TEs to a much greater extent than those conserved ones. In fact, ∼94% of TE-associated sites are nonconserved in mouse. Conversely, ∼5% of mouse poly(A) sites from ∼7% of genes surveyed are associated with TEs, of which ∼93% are not conserved in human (data not shown). This result indicates that TEs can significantly contribute to creation or modulation of poly(A) sites in evolution, and are responsible for species-specific poly(A) sites.Figure 3.

Bottom Line: We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved.We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized.Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Biomedical Sciences and Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

ABSTRACT
mRNA polyadenylation is an essential step for the maturation of almost all eukaryotic mRNAs, and is tightly coupled with termination of transcription in defining the 3'-end of genes. Large numbers of human and mouse genes harbor alternative polyadenylation sites [poly(A) sites] that lead to mRNA variants containing different 3'-untranslated regions (UTRs) and/or encoding distinct protein sequences. Here, we examined the conservation and divergence of different types of alternative poly(A) sites across human, mouse, rat and chicken. We found that the 3'-most poly(A) sites tend to be more conserved than upstream ones, whereas poly(A) sites located upstream of the 3'-most exon, also termed intronic poly(A) sites, tend to be much less conserved. Genes with longer evolutionary history are more likely to have alternative polyadenylation, suggesting gain of poly(A) sites through evolution. We also found that nonconserved poly(A) sites are associated with transposable elements (TEs) to a much greater extent than conserved ones, albeit less frequently utilized. Different classes of TEs have different characteristics in their association with poly(A) sites via exaptation of TE sequences into polyadenylation elements. Our results establish a conservation pattern for alternative poly(A) sites in several vertebrate species, and indicate that the 3'-end of genes can be dynamically modified by TEs through evolution.

Show MeSH