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

Nucleic Acids Res. 2008 Oct;36(17):5581-90. doi: 10.1093/nar/gkn540. Epub 2008 Aug 30.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Flanking Region*
  • 3' Untranslated Regions / chemistry
  • Alu Elements
  • Animals
  • Base Sequence
  • Chickens / genetics
  • Conserved Sequence
  • DNA Transposable Elements
  • Evolution, Molecular*
  • Genomics
  • Humans
  • Interspersed Repetitive Sequences*
  • Long Interspersed Nucleotide Elements
  • Mice
  • Phylogeny
  • Poly A / analysis
  • Polyadenylation*
  • Rats
  • Sequence Alignment
  • Short Interspersed Nucleotide Elements
  • Terminal Repeat Sequences

Substances

  • 3' Untranslated Regions
  • DNA Transposable Elements
  • Poly A