mRNA retrotransposition coupled with 5' inversion as a possible source of new genes

Mol Biol Evol. 2009 Jun;26(6):1405-20. doi: 10.1093/molbev/msp050. Epub 2009 Mar 16.

Abstract

Human long interspersed nuclear element-1 (L1) occupies one-sixth of our genome and has contributed to genome evolution in various ways. Approximately 10% of human L1 copies are composed of two L1 segments; the 5' segment and 3' segment are in head-to-head (i.e., 5'-inverted) orientation. Besides mediating their own retrotransposition, L1 has the ability to mobilize mRNA "in trans," and the number of retrotransposed mRNA sequences (retrocopies) is estimated to be >6,000. In this study, we identified 48 human-specific retrocopies and 95 chimpanzee-specific retrocopies by comparing the human and chimpanzee genomes. Among these retrocopies, 12 were 5'-inverted. The characteristics of these 5'-inverted retrocopies were similar to those of 5'-inverted L1 copies, indicating that the 5' inversion is generated by the same mechanism. With these findings, we examined the possibility that 5' inversion of the retrocopy generates a new gene that codes for a peptide with a different N terminus. We identified several potential 5'-inverted retrogenes, including those of thymopoietin beta (TMPO) and eukaryotic translation initiation factor 3 subunit 5 (EIF3F). The most interesting candidate was the 5'-inverted retrocopy of small nuclear ribonucleoprotein polypeptide N (SNRPN). This retrocopy was transcribed in the reverse orientation in several organs, had multiple transcript variants, and encoded a protein containing a peptide fragment derived from the N-terminal portion of SNRPN. Our results suggest that mRNA retrotransposition coupled with 5' inversion may be a mechanism to generate new genes distinct from parental genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chloride Channels / genetics
  • Chloride Channels / metabolism
  • Chromosome Inversion / genetics*
  • Evolution, Molecular*
  • Hominidae / genetics
  • Humans
  • Long Interspersed Nucleotide Elements / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA, Messenger / genetics*
  • Species Specificity
  • Thymopoietins / genetics
  • Thymopoietins / metabolism

Substances

  • CLIC4 protein, human
  • Chloride Channels
  • Nuclear Proteins
  • RNA, Messenger
  • Thymopoietins
  • TMPO protein, human