Successful COG8 and PDF overlap is mediated by alterations in splicing and polyadenylation signals

Hum Genet. 2012 Feb;131(2):265-74. doi: 10.1007/s00439-011-1075-9. Epub 2011 Jul 30.


Although gene-free areas compose the great majority of eukaryotic genomes, a significant fraction of genes overlaps, i.e., unique nucleotide sequences are part of more than one transcription unit. In this work, the evolutionary history and origin of a same-strand gene overlap is dissected through the analysis of COG8 (component of oligomeric Golgi complex 8) and PDF (peptide deformylase). Comparative genomic surveys reveal that the relative locations of these two genes have been changing over the last 445 million years from distinct chromosomal locations in fish to overlapping in rodents and primates, indicating that the overlap between these genes precedes their divergence. The overlap between the two genes was initiated by the gain of a novel splice donor site between the COG8 stop codon and PDF initiation codon. Splicing is accomplished by the use of the PDF acceptor, leading COG8 to share the 3'end with PDF. In primates, loss of the ancestral polyadenylation signal for COG8 makes the overlap between COG8 and PDF mandatory, while in mouse and rat concurrent overlapping and non-overlapping Cog8 transcripts exist. Altogether, we demonstrate that the origin, evolution and preservation of the COG8/PDF same-strand overlap follow similar mechanistic steps as those documented for antisense overlaps where gain and/or loss of splice sites and polyadenylation signals seems to drive the process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics*
  • Animals
  • Base Sequence
  • Evolution, Molecular*
  • Genes, Overlapping*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Polyadenylation*
  • RNA Splicing*
  • Rats


  • Adaptor Proteins, Vesicular Transport
  • COG8 protein, human
  • Nerve Tissue Proteins
  • PDF protein, human