Associations of alternative poly(A) sites with transposable elements

Previously, I discussed alternative polyadenylation, noting the extent (as many as 50% of human genes) of the phenomenon.  While there is some conservation of patterns of alternative poly(A) sites in animals, many of these events are species specific.  This suggests a relatively active evolutionary dynamic, one that shapes mRNAs in many ways.  A soon-to-be published study recently-published study in Nucleic Acids Research shed light on this dynamic, showing that species-specific poly(A) sites are often associated with transposable elements (TEs).  The abstract of the paper:

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.

A few items of interest:

Each major class of transposon (LINE, SINE, LTR, DNA) is associated with poly(A) sites.  Moreover, each class possesses potential cis elements (discussed here) that might contribute to poly(A) site functionality.  However, by and large, TE-associated sites do not seem to be “strong” (based on analysis of cDNA and EST sequence collections, at least).  Thus, TEs would seem to “work” by adding partial (weak) functionality to adjacent sequences; the nature of the neighboring sequences and/or genetic drift would seem to affect both functionality and perhaps fixation of the TE-associated site.

Consistent with the association with TEs (whose number increases and positions vary with evolutionary “age”), alternative polyadenylation seems to be more prevalent in older genes.

TE-associated poly(A) sites are not as likely to be conserved in animals as alternative sites not obviously associated with TEs.  This suggests that TE-associated alternative poly(A) sites are probably neutral or deleterious in terms of their effects on gene expression.  However, the high frequency of such sites raises the possibility that the occasional TE-associated site may have immediate selectable impact, or may acquire impact via drift.  As indicated previously, alternative polyadenylation can have substantial significance; thus, TEs may afford yet another way by which gene expression may vary over evolutionary times.  In other words, yet another possible mechanism of regulatory evolution.  Time (and further experimentation) will tell about this latter intriguing possibility.

Lee et al. speculate that conserved alternative poly(A) sites, while not associated with identifiable TEs, may have their origins with TEs; in these cases, the respective elements may have drifted into unidetifiabbilit.  Such a position would draw the wrath of Larry Moran, as they are clearly “adaptationists” when it comes to the significance of TE-associated alternative poly(A) sites.  Ara et al. (BMC Genomics 7, 189, 2006) take a more guarded and realistic approach to the matter of functionality of non-conserved poly(A) sites.

The citation:

J. Y. Lee, Z. Ji, B. Tian (2008). Phylogenetic analysis of mRNA polyadenylation sites reveals a role of transposable elements in evolution of the 3′-end of genes Nucleic Acids Research, 36 (17), 5581-5590 DOI: 10.1093/nar/gkn540