Birth of protein-coding exons by ancient domestication of LINE retrotransposon

Transposons, occasionally domesticated as novel host protein-coding genes, are responsible for the lineage-specific functions in vertebrates. LINE-1 (L1) is one of the most active transposons in the vertebrate genomes. Despite its abundance, the contribution of L1 to the birth of vertebrate proteins remains unelucidated. Here, we present a novel mechanism for the origination of de novo proteins, in which the L1 retrotransposons are incorporated into host genes as protein-coding exons by alternative splicing. L1 ORF1 protein (ORF1p) is an RNA-binding protein that binds to L1 RNA and is required for retrotransposition by acting as an RNA chaperone. We identified a splicing variant of myosin light chain 4 ( MYL4 ) containing an L1 ORF1-derived exon and encoding a chimeric protein of L1 ORF1p and MYL4, named Lyosin. Molecular evolutionary analysis revealed that Lyosin was acquired in the common ancestor of reptiles and birds during the Paleozoic era. The amino acid sequence of Lyosin had undergone purifying selection although it was lost in some lineages, including the Neognathae birds and snakes. The transcripts encoding Lyosin were expressed in the testes of two lizard species, suggesting that its function is different from that of the canonical MYL4 expressed specifically in the heart. Furthermore, sequence searches revealed other evolutionarily conserved chimeric isoforms fused to the L1 ORF1p in three genes in vertebrates. Our findings suggest a novel evolutionary mechanism for the birth of lineage-specific proteins derived from transposons and implicate the previously unrecognized adaptive functions of L1 ORF1p.