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Nucleic Acids Research Advance Access published online on August 30, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn540
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular biology

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

Ju Youn Lee1,2, Zhe Ji1,2 and Bin Tian1,2,*

1Graduate School of Biomedical Sciences and 2Department of Biochemistry and Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA

*To whom correspondence should be addressed. Tel: +1 973 9 72 36 15; Fax: +1 973 9 72 55 94; Email: btian{at}umdnj.edu

Received July 14, 2008. Revised August 5, 2008. Accepted August 6, 2008.

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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