LTR-mediated retroposition as a mechanism of RNA-based duplication in metazoans

Abstract

In a broad range of taxa, genes can duplicate through an RNA intermediate in a process mediated by retrotransposons (retroposition). In mammals, L1 retrotransposons drive retroposition, but the elements responsible for retroposition in other animals have yet to be identified. Here, we examined young retrocopies from various animals that still retain the sequence features indicative of the underlying retroposition mechanism. In Drosophila melanogaster, we identified and de novo assembled 15 polymorphic retrocopies and found that all retroposed loci are chimeras of internal retrocopies flanked by discontinuous LTR retrotransposons. At the fusion points between the mRNAs and the LTR retrotransposons, we identified shared short similar sequences that suggest the involvement of microsimilarity-dependent template switches. By expanding our approach to mosquito, zebrafish, chicken, and mammals, we identified in all these species recently originated retrocopies with a similar chimeric structure and shared microsimilarities at the fusion points. We also identified several retrocopies that combine the sequences of two or more parental genes, demonstrating LTR-retroposition as a novel mechanism of exon shuffling. Finally, we found that LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. Transcriptional profiling coupled with sequence analyses revealed that the sense-strand transcription of the retrocopies often lead to the origination of in-frame proteins relative to the parental genes. Overall, our data show that LTR-mediated retroposition is highly conserved across a wide range of animal taxa; combined with previous work from plants and yeast, it represents an ancient and ongoing mechanism continuously shaping gene content evolution in eukaryotes.

The Genomic Impact of Gene Retrocopies: What Have We Learned from Comparative Genomics, Population Genomics, and Transcriptomic Analyses?

“…The template switching will occur if there are by chance regions of sequence similarity between the mRNA and the nascent cDNA (Derr et al 1991). When the template switching occurs more than once, chimeric retrocopies can be produced (Wang et al 2006; Tan et al 2016). These retrocopies or more often partial retrocopies will be flanked by LTR sequences on both sides.…”

“…Discoveries of LTR retroelement sequences flanking single genes in maize (Bureau et al 1994; Jin and Bennetzen 1994) have been followed by genome-wide investigations of LTR elements involved in retrogenes formation in rice (Wang et al 2006), Arabidopsis (Zhu et al 2016) and more recently of retroCNVs in animals (Tan et al 2016). It does seem that, as initially observed for the Ty1 element in yeast (fig.…”

Meiotic Sex Chromosome Inactivation: Compensation by Gene Traffic

“…While RPL10 was present in the ancestor of all eukaryotes more than one billion years ago, its paralogous copy, RPL10L, originated less than 160 million years ago in the common ancestor of eutherian mammals ( Figure 1A). The RPL10L gene originated via retroposition of a transcript of the multi-exon X-linked RPL10 gene, which was reversetranscribed and reintegrated into the genome, resulting in the loss of all introns in the copy [18,19]. RPL10, like many other ribosome proteins, is among the most conserved mammalian proteins [20], exhibiting only a single conservative substitution in the human lineage out of its 214 residues [17].…”

The mutational load in natural populations is significantly affected by high primary rates of retroposition

“…Full genome resequencing data of 96 individuals derived from nine natural populations corresponding to were used to assess gene retroposition events (Figure 1 and Supplementary Tables S1 and S2A). By adapting an exon-exon junction and exon-intron-exon junction mapping based approach for short read genomic sequencing data (18,19,25), we refined a computational pipeline to identify retroCNV genes (i.e., retroposed parental genes) (Supplementary Material Text S1 and Figure S1) including a power analysis for optimizing mapping conditions. A retroCNV gene is called, on condition that both the intron loss event and the presence of parental gene can be observed in the same individual sequencing dataset (25).…”