mRNA Retrotransposition Coupled with 5′ Inversion as a Possible Source of New Genes

摘要

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.