Mammalian genomes contain intronless DNA copies of more than 1,000 different spliced mRNAs, and some of these retrocopies have been converted into functional retrogenes by the processes outlined above [7
]. In their recent paper, Huang et al.
] provide insight into the creation of the retrogenes Rtdpoz-T1
(which will be referred to as T1
) in the rat genome. The 5' UTRs of these two genes have been the sites of multiple transposable element insertions, resulting in the generation of 11 different transcripts (isoforms). The RTdpoz
family of elements are distributed over seven different chromosomes of the rat genome but the bulk of them map over an approximately 700 kb segment on chromosome 2 (including T1
exons are derivatives of mostly repetitive sequences of L1 and ERV transposable elements, particularly in the T1
transcripts. The first exon of both genes is the result of exonization of the same transposable element, and both T1
are transcribed from a common promoter associated with this leader exon, which is located upstream of the retrogene. Thus, the exonization of a transposable element has resulted in transcriptional activation of the intronless T1
Interestingly, most mammalian retrogenes are expressed mainly in the testes, where their transcripts participate in spermatogenesis and other unique male germline functions. Transcription in testes appears to be less regulated than in other somatic tissues [8
], which might lead to a higher level of exonization of transposable elements in this organ. In support of this hypothesis, Huang et al.
] show that T1
are expressed exclusively in the testis and during early stages of embryonic development.
The authors also show that exonization within a retrogene can add new regulatory motifs and new protein-coding sequences. They find that some of the alternatively spliced transposable-element-derived exons located upstream of the original ATG translation start site of the retrocopy can provide a new open reading frame (ORF) and a new start codon. These insertions have both an influence on gene expression at the level of transcription, and in the T1 gene, the new ORF and ATG triplet also repress translation of the RNA transcript.
The study by Huang et al.
] adds a new twist to exonization: transposable elements not only provide functional sequences within genes, but they can also provide promoter sequences located upstream of retrocopies of intronless mRNA. Transcription from such sites results in mRNA precursors containing 5' UTR exon and intron sequence from the transposable element and the exon from the retrocopy gene. Splicing results in mRNAs that are 'live on arrival' as they maintain the coding capacity of the original gene. The fate of such new genes is determined by selective pressures during evolution.